CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 205641Orig1s000 ADMINISTRATIVE and CORRESPONDENCE DOCUMENTS Department of Health and Human Services Food and Drug Administration PATENT INFORMATION SUBMITTED WITH THE FILING NDA NUMBER OF AN NDA, AMENDMENT OR SUPPLEMENT 205-641 NAME OF non HOLDER For Each Patent That Claims a Drug Substance Mm? Sham 3? D?hmc Cm" (Active Ingredient), Drug Product (Formulation and Composition) and/or Method of Use The following is provided in accordance Section of 7 the Federal Food, Drug, and Cosmetic Act. TRADE NAME (OR PROPOSED TRADE NAME) HFA 100 Inhalation Aerosol; HFA 200 Inhalation Aerosol ACTIVE INGREDIENHS) Momctasonc Furoatc mometasonc furoatc 100 momctasone furoatc 200 FORM Inhalation Aerosol This patent declaration form is required to be submitted to the Food and Drug Administration (FDA) with an NDA application, amendment. or supplement as required by 21 CFR 314.53 at the address provided in 21 CFR Within thirty (30) days after approval of an MBA or supplement, or within thirty (30) days of issuance of a new patent, a new patent declaration must be submitted pursuant to 21 CFR with all of the required information based on the approved NDA or supplement. The information submitted in the declaration form submitted upon or after approval will be the only information relied upon by FDA for listing a patent in the Orange Book. For hand-written or typewriter versions of this report: If additional space is required for any narrative answer one that not require a "Yes" or "No" response). please attach an additional page referencing the question number. FDA will not list patent information if you file an incomplete patent declaration or the patent declaration indicates the aunt Is not eligible for listing. a; no; page small for "the pending non, some salami design and; ya; me sisal-ran infometion described below. if you are not submitting any patents for this pending NBA, amendment, or supplement, complete above section and sections 5 and 6. 1. sexism a. United States Patent Number b. Isws Date of Patent c. Expiration Date of Patent 6,068,832 May 30, 2000 August 27, 2017 6. Name ofPatent Owner Address (of Patent Owned Merck Sharp Dohmc Corp. Of?ce of General Counsel One Merck Drive - WS3B-70A, PO. Box 100 CityIStats Whitehoosc Station, NJ ZIP- Cods FAX Number (ifaveiiable) 08889 (908) 735-1249 Telephone Number E4Mail Address (908) 423-3761 o. who resides or main- Address (of agent or representatnle named in tains a place of business within the United States author- ized to receive notice of patent certi?cation under sedion 505(b)(3) and of the Federal Food. Drug. and Cosmetic Act and 21 CFR 314.52 and 314.95 (if patent CityIStats owner or MBA applicantlholder does not reside or have a ?Wm Win ZIP Code FAX Number (ilavar'lablsj Telephone Number E-Mail Address (if available) Is the patent referenced above a patent that has been submitted previously for the approved NDA or supplement referenced above? Yes No Q. lithe patent referenced above has been submitted previoust for listing. is the expiration I 7 date a new expiration date? Yes mo Substitute FORM FDA 3542a (32011) PI'll. 1 Reference ID: 3501120 For the patent referenced above, provide the following Information on the drug substance, drug product and/or method of use that Is the subject of the pending NBA, amendment, or supplement. 2.Drug Substance (Active Ingredient) 2.1 Does the patent claim the drug substance that is the active ingredient in the drug product described in the pending NDA, amendment or supplement? Yes ENO 2.2 Does the patent claim a drug substance that is a different polymorph of the active ingredient described in the pending NBA. amendment or supplement? Yes No 2.3 If the answer to question 2.2 is "Yes." do you certify that. as of the date of this declaration. you have test data demonstrating that a drug product containing the polymorph will perform the same as the drug product described in the The type oftest data required is described at 21 CFR 314.530?. Yes El No 2.4 Specify the polymorphic form(s) claimed by the patent for which you have the test results described in 2.3. 2.5 the patent claim only aimetaboli?te? of the active ingredient pending in the?noA or supplement? (Complete the information in section 4 below if the patent claims a pending method of using the pending drug product to administer the metabolite.) Yes IE No 2.6 7 the patent claim only an interrnecli'ate? Yes No 2.7 It the patent referenced in 2.1 isa' proddet-by?rocess patent. is the product claimed in the patent novel? (An answer is required only lfthe patent is a product-by-process patent.) Yes I No a. drug Product (Composl?oanonnulaticn) 3.1 does the patent claim the drug product. as de?nedin 21 CFR 314.3. in the pending amendment. 7 or supplement? I Yes No 3.2 Does the patent claim only an intermediate? - El Yes No 3.3. lfthe' patent 'referenced in 3.1 is a produ'ct-by-process patent. is the produd?claimed in the patent novel? (An answer is required only if the patent is a product-by-process patent) I I Yes _No 4. Mottled of Use I Sponsors must submit the-intonnation in section 4 for each method of using the pending drug product for-which approval is being sought that is claimed by the patent. For each pending method of use claimed by the patent, provide the following information: 4.1 the patent claim one or more methods of use for which approval is being sought in the pending NDA. amendment, or supplement? Yes N0 4.2 Patent Claim Nimbelts) (as listedirl thepalent) Does the?paten't ciaim(s) referenced in 4.2 claim a 8-14 Pending method of use for which approval is being sought In the pending NBA, amendment or supplement? Yes No 4.2a If the ansuler to 4.2 is Use: (Submit indication or method of user?nfonnatit?m as identi?ed speci?cally in the proposed labeling.) Wang: with indication and Usage: ASMANEX HFA is a corticosteroid indicated for: Maintenance treatment of asthma as use . . . with speci?c prophylactic therapy in patients l2 years of age or older. to the proposed labeling for the drug product. Substitute FORM FDA 35423 (3I2011) Page 2 Reference ID: 3501120 5. lie Relevant Patents For this pending NDA. memm, or supplement, there are no relevant patents that claim the drug substance (active ngredient). drug product (formulation or composition) or methodts) of use, for which the applicant is seeking approval and with rspect to which a claim of patent infringement could reasonably be asserted it a person not licensed by the owner oi-the es patent engaged in the manufacture. use. or sale of the drug product. Declaration Certification 6.1 The undersigned declares that this is an accurate and complete submission of patent information for the NBA, amendment, or supplement pending under section 505 of the Federal Food, Drug, and Cosmetic Act. This time-sensitive patent information is submitted pursuant to 21 CFR 314.53. iattest that i am familiar with 21 CFR 314.53 and this submission complies with the requirements- of the regulation. verily under penalty of perjury that the foregoing is true and correct. Warning: A willfully and knowingly false statement is a criminal offense under 18 0.8.6. 1001-. 0.2 Authorized Signature of NBA Applicantlt-lolder or Patent Owner (Attorney, Agent, Representative or Date Signed other Authorized Oli?icial) (Provide lnlonnation below) . {/20/2013 NOTE: Only an NBA applicantiholder may submit this declaration directly to the FDA. A patent owner who Is not the NDA applicant! holder ls authorized to sign the declaration but may not submit it directly to FDA. 21 CFR 314.53th4) and check applicable box and provide information below. NDA Applicantll-lolder NDA Applicant's/Holder's Attorney, Agent (Representative) or other Authorized Official Patent Owner Patent Owner's Attorney. Agent (Representative) or Other Authorized Of?cial Name Matthew A. chf, Director? Patents Address City/State Merck, PO. Box 2000, RY 86-2011A Rahway, NJ I I 1 Telephone 1 Number 07065-0907 732-594-1404 Number or available) 7 E-Maii Address (if available) 732-594-4720 The public reporting burden for this collection of information has been estimated to average 20 hours per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to: Food and Drug Administration CDER (RFD-007) 5600 Fishers Lane Rockville, MD 20857 An agency may not conduct or sponsor: and a person is not required to respond to. a collection of information miss: it displays a currently valid OMB control number. 1 Substitute FORM FDA 3542a (312011) Page 3 Reference ID: 3501120 Department of Health and Human Services Food and Drug Administration PATENT INFORMATION SUBMITTED WITH THE FILING OF AN NDA, AMENDMENT OR SUPPLEMENT For Each Patent That Claims a Drug Substance (Active Ingredient), Drug Product (Formulation and Composition) and/or Method of Use NDA 205-641 NAME OF NDA HOLDER Merck Sharp Dohme Corp. The following is provided in accordance with Section 505m) and of the Federal Food, Drug, and Cosmetic Act. TRADE NAME (OR PROPOSED TRADE NAME) HFA 100 Inhalation Aerosol; HFA 200 Inhalation Aerosol ACTIVE Momctasonc Furoatc mometasone furoatc 100 momctasonc furoatc 200 DOSAGE FORM Inhalation Aerosol upon by FDA for listing a patent in the Orange Book. This patent declaration form is required to be submitted to the Food and Drug Administration (FDA) with an NDA application, amendment. or supplement as required by 21 CFR 314.53 at the address provided in 21 CFR Within thirty (30) days after approval of an NDA or supplement. or within thirty (30) days of issuance of a new patent, a new patent declaration must be submitted pursuant to 21 CFR with all of the required information based on the approved NDA or supplement. The information submitted in the declaration form submitted upon or after approval will be the only information relied I For hand-written or typewriter versions of this report: if additional space is required for any narrative answer one that does not require a "Yesf' or "No" response). please attach an additional page referencing the question number. patent is not eligible for listing. FDA will not list patent information if you file an incomplete patent declaration or the patent declaration indicates the complete above section and sections 5 and 6. i=6} an pant gamma the pending NDA, means: or supplement magma awe; you' an: st:me an the? informatitm described below. if you are not submitting any patents for this pending NDA, amendment, or supplement, (908) 423-3761 1. GENERAL a. United States Patent Number b. Issue Date of Patent c. Expiration Date Of Patent 6,057,307 May 2, 2000 January 27, 2014 Name of Patent Owner I Address (of Patent Owner) Merck Sharp Dohme Corp. O?icc of General Counsel Onc Merck Drive - PO. Box 100 Whitehousc Station, NJ ZIP Code FAX Number (if available) 08889 (908) 735-1249 Telephone Number E?Maii Address (if available) paul matukaitis@merck.com 6- WW who resides or main- tains a place of business within the United States author- ized to receive notice of patent certi?cation under section 505(b)(3) and of the Federal Food. Drug. and Address (of agent or representative named in 1. e. CosmeticAct and 21 CFR 314.52 and 314.95 (it patent CityIState owner or NDA applicantlholder does not reside or have a place of business within the United States) ZIP code FAX Number (if available) Telephone Number E-Mail Address (if available) f. Is the patent referenced above a patent that has been submitted previously for the approved NDA or supplement referenced above? Yes N0 9. lithe patent referenced above has been submitted previously for listing. is the expiration date a new expiration date? Yes No Substitute FORM FDA 35423 (32011) Reference ID: 3501120 Page1 For the parent referenced above, provide the following lnfannadon on the drug substance, drug product and/or method of use that Is the subject of the pending NBA, amendment, or supplement 2r.j Drug Substance (Active ingredient) Does the patent claim the drug substance that is the active ingredient in the drug product described in the pending NDA, amendment or supplement? Yes No 2.2 Does the patent claim a drug substance that is a different polymorph of the active ingredient described in the pending NDA, amendment or supplement? Yes No 2.3 If the answer to question 2.2 is "Yes." do you certify that. as of the date of this declaration, you have test data demonstrating that a drug product containing the polymorph will perform the same as the drug product described in the The type attest data required is described at 21 CFR 314.5303). [3 Yes No 2.4 Specify the polymorphic form(s) claimed by the patent for which you have the test results described in 2.3. 2.5 Does the patent claim only a metabolite dime active ingredient pending in the NDA or supplement? (Complete the information in section 4 below if the patent claims a pending method of using the pending drug product to administer the metabolite.) Yes No 2.6 Does the patent claim only an intermediate? Yes No 2.1 it the patent referenced in 2.1 is a product-by-process patent. is the product claimed in the patent novel? (An answer is required only ifthe patent is a pmdud-by-prooess patent.) I 7 Yes No 7 Product (Composltto?nll-?ormulattonl l.1 Does the patent claim the drug product, as de?ned in 21 CFR 314.3. in the pending NDA. amendment, or supplement? Yes No 3.2 Does the patent claim only an intermediate? Yes No If the patent referenced in 3.1 is a product?by-process patent. is the product claimed in the patent novel? (An answer is required only itthe patent is a product~by-prooess patent) Yes No Use I Sponsors must submit the information in section 4 for each method of using the pending drug product for which approval is being sought diet Is claimed by the patent. For each pending method of use claimedby the patent, provide the following information: 4.1 Does the patent claim one or more methods of use for which approval is being sought in the pending amendment. or supplement? - Yes NO 4.2 Patent Claim Nimbeds) (aslistedin diaper-no Does (Do) the patent claim(s) referenced in 4-.2 claim a l-3, 10-12, 14-15, 17-20, 22-23 Pending method of use for which approval is being sought In the pending NBA. amendment or supplement? Yes No 4.2: if the answer to 4.2 is Use: (Submit indication or method of use infometion as identi?ed specifically in the proposed labeling.) With Indications and. Usage: ASMANEX HFA is a corticosteroid indicated for: Maintenance treatment of asthma as spea?crty use - - - . with 3 reference prophylactic therapy in patients 12 years of age and older. to the proposed labeling for the drug product. Substitute FORM FDA 3542: (312011) Page 2 Reference ID: 3501120 5. No Relevant Patents For this pending NDA. amendment. or supplement, there are no relevant patents that claim the drug substance (active ingredient). drug product (formulation or composition) or methodls) of use. for which the applicant is seeking approval and with Yes respect to which a claim of patent infringement could reasonably be asserted if a person not licensed by the owner of the patent engaged in the manufacture, use. or sale of the drug product. 6i;?beclaration Certi?cation 8.1 The undersigned declares that this is an accurate and complete submission of patent information for the NDA, amendment, or supplement pending under section 505 of the Federal Food, Drug, and Cosmetic Act. This time-sensitive patent information is submitted pursuant to 21 CFR 314.53. I attest that lam familiar with 21 CFR 314.53 and this submission complies with the requirements of the regulation. I verify under penalty of perjury that the foregoing is true and correct Warning: A willfully and knowingly false statement is a criminal offense under 18 U.S.C. 1001. 6.2 Authorized Signature of NBA Applicant/Holder or Patent Owner (Allomey. Agent. R'epresentabire or Date Signed other Authorized O?icial) (Provide lnfonnatlon below) %4 6/20/20/5 NOTE: Onlyan NBA applicantlholder may submit this declaration directly to the FDA. A patent owner who is not the NDA applicant! holder is authorized to sign the declaration but may not submit it directly to FDA. 21 CFR and (dim. Check applicable box and provide information below. El NDA ApplicantIHolder NDA Attorney, Agent (Representative) or other Authorized Of?cial [3 Patent Owner Patent Owner?s Attorney. Agent (Representative) or Other Authorized Of?cial Name Matthew A. chf, Director - Patents Address Merck, P.O. Box 2000, RY 86-2011A RahWay, NI ZIP Code I I I I Telephone Number 07065-0907 732-594-1404 FAX Number (if available) 7 E-Mail Address (rial/arrears) 732?594-4720 The public reporting burden for this collection of inforrnation has been estimated to average 20 hours per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of Information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to: Food and Drug Administration CDER (RFD-007) 5600 Fishers Lane Rockvillc, MD 20857 An agency may not conduct or sponsor, and a person is not required to respond to, a collection of informlion unless it displays a currently valid OMB control number. Substitute FORM FDA 35423 (312011) Page 3 Reference ID: 3501120 Department of Health and Human Services Food and Drug Administration PATENT INFORMATION SUBMITTED WITH THE FILING NDA NUMBER OF AN NDA, AMENDMENT OR SUPPLEMENT 205-641 NAME OF NDA HOLDER For Each Patent That Claims 3 Drug Substance Merck Sharp 8? Dame emp- (Active Ingredient), Drug Product (Formulation and Composition) and/or Method of Use The following is provided in accordance with Section 505(b) and of the Fedora;i Food, Drug, and Cosmetic Act. TRADE NAME (OR PROPOSED TRADE NAME) HFA 100 meg Inhalation Aerosol; HFA 200 Inhalation Aerosol ACTIVE (S) Mometasonc Furoatc mometasonc furoatc 100 mometasone ?u'oatc 200 meg DOSAGE FORM Inhalation Aerosol This patent declaration form is required to be submitted to the Food and Drug Administration (FDA) with an NDA application. amendment. or supplement as required by 21 CFR 314.53 at the address provided in 21 CFR thhin thirty (30) days after approval of an NBA or supplement. or within thirty (30) days of issuance of a new patent, a new patent declaration must be submitted pursuant to 21 CFR with all of the required information based on the approved NDA or supplement. The information submitted in the declaration form submitted upon or after approval will be the only information relied upon by FDA for listing a patent in the Orange Book. For hand-written or typewriter versions of this report: If additional space is required for any narrative answer one that does not require a "Yes" or "No" response). please attach an additional page referencing the question number. FDA will not list patent information if you file an incomplete patent declaration or the patent declaration indicates the ttent is not eligible for listing. For each patent-subrnitted for tho I pending NDA. amendment or supplement referenced above. you must submit all ?the information described below. if you are not submitting any patents? for this pending NDA, amendment, or supplement, complete above section and sections 5 and 6. 1. GENERAL a. United States Patent Number b. Issue Date of Patent c. Expiration Date of Patent 5,889,015 March 30, 1999 January 27. 2014 d. Name of Patent Owner Address {of Patent Owned Merck Sharp Dohme Corp. Of?ce of General Counsel One Merck Drive - WS3B-70A, PO Box 100 Whitehousc Station, NJ ZIP Code FAX Number (if available) 08889 (908) 735-1249 Telephone Number E-Mail Address (if available) (908)423-3761 pan] matuicaitis@merclt.com e. who resides or main- Address (ofegent orrepresentative named in to.) tains a place at business within the United States author- ized to receive notice of patent codi?cation under section 505(b)(3) and of the Federal Food. Drug. and Cosmetic Act and 21 CFR 314.52 and 314.95 (it patent owner or NDA applicantlholder does not reside or have a place of business within the United States) ZIP Code FAX Number Managua) Telephone Number E-Mail Address (ifaveilable) Is the patent referenced above a patent that has been submitted previously for the approved NDA or supplement referenced above? Yes No 7 g. If the patent referenced above has been submitted previously for listing. is the expiration date a new expiration date? Yes No Substitute roan FDA 3542: (312011) Page 1 Reference ID: 3501120 For the patent referenced above, provide the following information on the drug substance, drug product and/or method of use that is the subject of the pending NDA, amendment, or supplement. 2. Drug Substance (Active Ingredient) 2.1 Does the patent claim the drug substance that is the active ingredient in the drug product described in the pending NDA. amendment or supplement? Yes No 2.2 Does the patent claim a drug substance that is a different polymorph of the actiVe ingredient described in the pending NDA, amendment or supplement? Yes No 2.3 If the answer to question 2.2 is "Yes," do you certify that. as of the date of this declaration. you have test data demonstrating that a drug product containing the polymorph will perform the same as the drug product described in the The type or test data required is described at 21 CFR 314.530?. Yes No 2.4 Specify the potyrnorphic forrn(s) claimed by the patent for which you have the test results described in 2.3. Does the patent claim only a metabolite of the acthre ingredient pending in the MBA or supplement? (Complete the information in section 4 below if the patent claims a pending method of using the pending drug product to administer the metabolite.) Yes No 2.6" the patent claim only an'interrned'iate? Yes No 2.7 If the patent refaenced in 2.1 is a product-by-process patent. is the product claimed in the patent novel? (An answer is required only 'rfthe patent is a product-by-process patent.) Yes No 3. ping Product (CompOsitioanormulation) 3.1 Does the patent claim the drug product, as'defined in 21 CFR 314.3. in the pending NDA, amendment. or supplement? [3 Yes No 3.2 Does the'patent claim only an intermediate? Yes No 3.3 If the patent referenced in 3.1 is a product-by-process patent. is the product claimed in the patent novel? (An answer is required only ifthe patent is a product-by-prooess patent.) I Yes No {Method of Use Sponsors must submit the infonnation in section 4 for each method of using the pending drug product for which approval is being sought that is claimed by the patent. For each pending method of use claimed by the patent. provide the following information: 4.1 Does the patent claim one or more methods of use for which approval is being sought in the pending NDA. amendment. or supplement? Yes No 4.2 Patent Cla'm Number(s) (as listed in the patent) Does (Do) the patent claim(s) referenced in 4.2 claim a 1-5, 31-33, 35 Pending method of use for which approval is being sought in the pending NDA, amendment or supplement? Yes No 4.2a If the answer to 4.2 is Use: (Submit indication or method of use infonnetion as identi?ed speci?cally in the proposed labeling.) "Yesfgg'?ry With Indications and Usage: ASMANEX HFA is a corticosteroid indicated for: Maintenance treatment of asthma as a use . . reference prophylactic therapy 1n patients 12 years of age and older. to the proposed labeling for the drug product. Substitute FORM FDA 3542a (312011) Page 2 Reference ID: 3501120 5. No Relevant Patents For this pending NDA. amendment. or supplement. there are no relevant patents that claim the drug substance (active 'gredient). drug product (formulation or composition) or method(s) of use, for which the applicant is seeking approval and with spect to which a claim of patent infringement could reasonably be assorted if a person not licensed by the owner of the patent engaged in the manufacture. use. or sale of the drug product. DYes 6. Declaration Certi?cation and correct. 6.1 The undersigned declares that this is an accurate and complete submission of patent information for the NDA, amendment, or supplement pending under section 505 of the Federal Food, Drug, and Cosmetic Act. This time-sensitive patent information is submitted pursuant to 21 CFR 314.53. attest that i am familiar with 21 CFR 314.53 and this submission complies with the requirements of the regulation. I verify under penalty of perjury that the foregoing is true Warning: A willfully and knowingly false statement is a criminal offense under 1'8 use. 1001. 6.2 other Authorized Of?cial} (Provide information below) Authorized Signature of NBA ApplicanilHolder or Patent Owner (Attomey. Agent, Representative or %4 Date Signed (?u/20 I3 NOTE: Only an NBA applicantlhoider may submit this declaration directly to the FDA. A patent owner who is not the NDA applicant! holder is authorized to sign the declaration but may not submit It directly to FDA. 21 CFR 314.53fcx4) and (one). Check applicable box and provide information below. NDA ApplicantlHolder NDA Applicant?siHolder's Attorney, Agent (Representative) or other Authorized Official El Patent Owner Patent Owner's Attorney. Agent (Representative) or Other Authorized- Of?cial Name Matthew A. Director - Patents Address Merck, P.O. Box 2000, RY 86-2011A Rahway, NJ ZIP Code Telephone Number 07065-0907 732-594-1404 FAX Number (if available) E-Mail Address {if available) 732?594-4720 Substitute FORM FDA 3542: ($2011) Reference ID: 3501120 The public reporting burden for this collection of information has been estimated to average 20 hours per response, including. the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of mfonnatton. Send comments regarding this burden estimate or any other aspect of this collection of infomation, including suggestions for reducing this burden to: Food and Drug Administration CDER (RFD-007) 5600 Fishers Lane Rockvillc, MD 20857 An agency nunr not conduct or sponsor, and a person is not required to respond to, a collection of iry'ormation unless it displays a currently valid OMB control number. Page3 Department of Health and Human Services Food and Drug Administration PATENT INFORMATION SUBMITTED WITH THE FILING NDA NUMBER OF AN NDA, AMENDMENT OR SUPPLEMENT 205-641 NAME OF APPLICANT I NDA HOLDER For Each Patent That Claims a Drug Substance Mm" Sham 9"th (30?9- (Actlve Ingredient), Drug Product (Formulation and Composition) and/or Method of Use The following is provided in accordance wl?r Section 505(b) and of the Federal Food, Drug, and Cosmetic Act. TRADE NAME (OR PROPOSED TRADE NAME) HFA 100 Inhalation Aerosol; HFA 200 Inhalation Aerosol ACTIVE Mometasone Furoate mometasone furoate 100 mometasone female 200 DOSAGE FORM Inhalation Aerosol This patent declaration form is required to be submitted to the Food and Drug Administration (FDA) with an NBA application, amendment, or supplement as required by 21 CFR 314.53 at the address provided in 21 CFR Within thirty (30) days after approval of an NBA or supplement. or within thirty (30) days of issuance of a new patent, a new patent declaration must be submitted pursuant to 21 CFR with all of' the required information based on the approved MBA or supplement. The information submitted in the declaration form submitted upon or after approval will be the only information relied upon by FDA for listing a patent in the Orange Book. For hand-written or typewriter versions of this report: if additional space is required for any narrative answer one that does not require a "Yes" or "No" response). please attach an additional page referencing the question number. FDA will not list patent information if you file an incomplete patent declaration or the patent declaration indicates the patent is not eligible for listing. I each submitted for the pending NDA, amendment or supplement referenced above, you must Submit all the information described below. if you are not submitting any patents for this pending NBA, amendment, or supplement, complete above section and sections 5 and 6. a. United States Patent Number b. Issue Date of Patent 0. Expiration Date of Patent 6,677,323 January 13, 2004 January 27, 2014 I d. Name of Patent Owner Address (of Patent Owned Merck Sharp Dohme Corp. O??ice of General Counsel One Merck Drive - W83 P.O. Box 100 CityIState Whitehousc Station, NJ ZIP Code FAX Number (if available) 08889 (908) 735?1249 Telephone Number E-Mail Address (ifavailable) (908) 423-3761 paul matukaitis@merck.com a. Name of agent gr roo?ntative who resides or main Address (of agent or representative named in tains a place of business within the United States author- ized to receive notice of patent certi?cation under section 505(b)(3) and of the Federal Food, Drug. and Cosmetic Act and 21 CF 314.52 and 314.95 (if patent owner or NDA applicantihoider does not reside or have a place of business within the United States) ZIP Code FAX Number (if availabb) Telephone Number E?Mail Address (if available) f. Is the patent referenced above a patent that has been submitted previously for the approved NDA or supplement referenced above? Yes No 9. If the patent referenced above has been submitted previously for listing. is the expiration date a new expiration date? Yes No Substitute FORM FDA 3542a (312011) Page 1 Reference ID: 3501120 For the patent referenced above, provide the following informadon on the drug drug product and/or method afuse that is the subject of the pending NDA, orsupplement 2. drug Substance (Active Ingredient) 1 Does the patent claim the drug substance that is the active ingredient in the drug product described in the pending NDA. amendment or supplement? Yes No 2.2 Does the patent claim a drug substance that is a different polymorph of the active ingredient described in the pending NDA. amendment or supplement? Yes No 2.3 It the answer to question 2.2 is "Yes." do you certify that. as of the date of this declaration. you have test data demonstrating that a drug product containing the potymorph will perform the same as the drug product described in the The type of test data required is described at 21 CPR Yes El No 2.4 Specify the polymorphic lonn(s) claimed by the patent for which you have the test results described in 23. 2.5 Does the patent Claim only a metabolite of the active ingredient pending in the NDA er supplement? (Complete the infonnatlon in section 4 below if the patent claims a pending method of using the pending product to administer the metabolite.) Yes No 2.6 D'oes the patent claim only an intermediate? Yes No 2.1- If the patent referenced in 2.1 is a product-by-process patent. is the product claimed in the patent novel? (An answer is required only if the patent is a patent.) I Yes 1. Product (CompositionIFormulatlon) 1 Does the patent claim the drug product. as de?ned in 2t CFR 314.3. in the pending NDA. amendment. or supplement? Yes No 3.2 Does the patent claim only an intermediate? Yes No 3.3 if the patent referenced in 3.1 is a product-by-process patent. is the product claimed in the patent novel? (An answer is required only ifthe patent is a product-by-process patent.) Yes No 4; cities I Sponsors must submit the information in section 4 for each method of using the pending drug product for which approval is being sought that Is claimed by the patent. For each pending method of use claimed by the patent. provide the following information: 4.1 Does the patent claim one or more methods of use for which approval is being sought in the pending NDA. amendment. or supplement? Yes No 4.2 Patent Cia'm Numbeds) (as Estedin thepatent} Does (Do) the patent claimls) referenced in 4.2 claim a l, 3, 5-6, 8, 11 Pending method of use for which approval is being sought In the pending NDA, amendment or supplement? Yes No 4.2: lithe answer to 4.2 is Use: (Submit initiation or method of use information as identi?ed speci?cally in the proposed labeling.) With Indication and Usage: ASMANEX HFA is a corticosteroid indicated for: Maintenance treatment of asthma as spe use - - - with spam Maren? prophylactic therapy in patients 12 years of age or older. to the proposed labeling for the product. Substitute FORM FDA 3542a (312011) Pace 2 Reference ID: 3501120 5. No Relevant Patents For this pending NDA. amendment. or supplement. there are no relevant patents that claim the substance (active ingredient). drug product (formulation or composition) or method(s) of use. for which the applicant is seeking approval and with Yes respect to which a claim of patent infringement could reasonably be asserted if a person not licensed by the owner of the patent engaged in the manufacture. use, or sale of the drug product. specializes-n :Cerli?catien 6.1 The undersigned declares that this Is an accurate and complete submission of patent information for the NDA, amendment, or supplement pending under section 505 of the Federal Food, Drug, and Cosmetic Act. This time-sensitive patent Information is submitted pursuant to 21 CFR 314.53. i attest that i am familiar with 21 CFR 314.53 and this submission complies with the requirements of the regulation. I verify under penalty of pedury that the foregoing is true and correct. Warning: A willfully and knowingly false statement is a criminal offense under 18 0.8.6. 1001. 6.2 Authorized Signature of NBA Applicant/Holder or Patent Owner (Attorney, Agent, Representative or Date Signed other Authorized Of?cial) (Provide Information below) 4/20 20/25 NOTE: Only an NBA applicantlholder may submit this declaration directly to the FDA. A patent owner who is not the NDA applicant)l holder is authorized to sign the declaration but may not submit it directly to FDA. 21 CFR and Check applicable box and provide information below. NDA Applicant/Holder NDA Applicant?slHolder's Attorney. Agent (Representative) or other Authorized Of?cial Patent Owner Patent Owner?s Attorney. Agent (Representative) or Other Authorized Of?cial Name Matthew A Left, Director Patents Address City/State Merck, P.O. Box 2000, RY 86-2011A Rahway, NJ ZIP Code I I Telephone Number 07065-0907 732-594-1404 FAX Number (ifavailable) I E?Mail Address (if available) 732-594-4720 The public reporting burden for this collection of information has been estimated to average 20 hours per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of infonnation. Send cemments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to: Food and Drug Administration CDBR (RFD-007) 5600 Fishers Lane Rockville, MD 20857 An agency may not conduct or sponsor, and a person is not required to respond to. a collection of infer-nutter! unless it displays a currenth valid OMB control number: Substitute FORM FDA 3542a (312011) Page 3 Reference ID: 3501120 Department of Health and Human Services Food and Administration PATENT INFORMATION SUBMITTED WITH THE FILING non. NUMBER OF AN AMENDMENT OR SUPPLEMENT 205-541 7 NAME OF APPIJCANT I NDA HOLDER For Each Patent That Claims a Drug Substance Mm? Sharp D?hm? (Active Ingredient), Drug Product (Fonnuialion and Composition} and/or Method of Use The following is provided in accordance with Section 5050)) and of the Federal Food, Drug, and Cosmetic Act. TRADE NAME (OR PROPOSED TRADE NAME) HFA 100 Inhalation Aerosol; HFA 200 Inhalation Aerosol ACTIVE Mometasonc Furoatc momctasonc furoatc 100 mornctasonc furoatc 200 DOSAGE FORM Inhalation Aerosol This patent declaration form is required to be submitted to the Food and Drug Administration (FDA) with an NBA application. amendment. or supplement as required by 21 CFR 314.53 at the address provided in 21 CFR Within thirty (30) days after approval of an MBA or supplement, or within thirty (30) days of issuance of a new patent, a new patent declaration must be submitted pursuant to 21 CFR with all of the required information based on the approved NDA or supplement. The information submitted in the declaration form submitted upon or after approval will be the only information relied upon by FDA for listing a patent in the Orange Book. For hand-written or typewriter versions of this report: If additional space is required for any narrative answer one that does not require a ?Yes? or "No" response), please attach an additional page referencing the question number. FDA will not list patent informadon if you file an incomplete patent declaration or the patent declaration indicates the - ?etent is not eligible for listing. r?or each patent submitted for the pendinn RDA, amendrnent or supplementre?ferenced seems.) most sham all the information described below. if you are not submitting any patents for this pending NDA, amendment, or supplement, complete above section and sections 5 and 6. GENERAL. a. United States. Patent Number b. Issue Date of Patent c. Date of Patent 6,365,531 April 2, 2002 January 27, 2014 d. Name or Patent Owner Address (ofPatent Owned Merck Sharp Dohmc Corp. Of?ce of General Counsel One Merck Drive - PO. Box 100 capsule Whitehousc Station. NJ ZIP Code FAX Number (if available) 08889 (908) 735-1249 Telephone Number E-Mail Address (liaveilable) (908) 423-3761 paul matukaitis@merck.com e. who resides or main- Address (of agent or representative named in 1.9.) tains a place of business within the United States author- ized to receive notice of patent certi?cation under section 505(c)(3) and oi the Federal Food. Drug. and CosmetieAct and 21 CFR 314.52 and 314.95 (if patent owner or NDA applicantlholder does not reside or have a place of business within the United States) Zip Cod. FAX Number (if available) Telephone Nunber E-Mail Address (if available) Is the patent referenced above a patent that has been submitted previously for the approved MBA or supplement referenced above? I Yes 8 No If the patent referenced above has been submitted previously for listing, is the expiration I date a new. expiration date? El", Substitute roan FDA 3542: (31201 1) Page 1 Reference ID: 3501120 that is the subject of the pending NDA, amendment, or supplement. For the patent referenced above, provide the following lnfomratfon on the drug substance, drug product and/or method of use 2. Drug Substance (Active Ingredient) 2.1 Does the patent claim the drug substance that is the active ingredient in the drug product patent novel? (An answer is required only if the patent is a product-by-prooess patent.) described in the pending NDA, amendment or supplement? Yes No 2.2 Does the patent claim a drug substance that is a different polymorph of the active ingredient described in the pending NDA. amendment or supplement? Yes No 2.3 lithe answer to question 2.2 is "Yes." do you certify that, as of the date of this declaration. you have test data demonstrating that a drug product containing the polymorph will perform the same as the drug product described in the The type oftest data required is described at 21 CFR 314.5303). Yes No 2.4 Specify the polymorphic form(s) claimed by the patent for which you have the test results described in 2.3. 2.5 Does the patent claim only a metabolite of the active ingredient pending in the NDA or sirpplement? (Complete the information in section 4 below if the patent claims a pending method of using the pending drug product to administer the metabolite.) Yes No 2.6 Does the patent claim only an intermediate? Yes No 2.7 If the patent referenced in 2.1 is a product-by-pr'ocess patent. is the product'claimed in the patent novel? (An answer is required only 'rlthe patent is a product-byprocess patent.) Yes No 3. Drug Product (Compositioanor-mulation) 3.1 Does the patent claim the product. as defined in 21 CFR 314.3, in the pending NDA. amendment. or supplement? Yes No 3.2 Does the patent claim only an intermediate? El Yes No 3.3 lithe patent referenced'in 3.1 is a product-by-process patent, is the preduct claimed in the Yes No mauled of Use Sponsors must submit the intonnation in section 4 for each method of using the pending drug product for which approval is being sought that is claimed by the patent. For each pending method of use claimed by the patent, provide the following information: 4.1 Does the patent claim one or more methods of use for which approval is being sought in the pending NDA. amndment. or supplement? Yes No 4.2 Patient Cla'm Nunberts) (as listed in the patent) Does (Do) the patent claim(s) referenced in 4.2 claim a 1?3, 10-12, 14-16, 18-21, 23-24 Pending method of use for which approval is being sought In the pending NDA, amendment or supplement? Yes No 4.2: If the answer to 4.2 is "Yes," identify with speci?city the use with speci?c reference to the proposed labeling for the drug product. prophylactic therapy in patients 12 years of age or older. Use: (Submit indication or method of use information as identi?ed speci?cally in the proposed labeling.) Indication and Usage: ASMANEX HFA is a corticosteroid indicated for: Maintenance treatment of asthma as Substitute FORM FDA 3542a (3I2011) Reference ID: 3501120 Page 2 5. No Relevant Patents For this pending NDA, amendment, or supplement, there are no reievant patents that claim the drug substance (active igredient), drug product (formulation or composition) or method(s) of use, for which the applicant is seeking approval and with Yes spent to which a claim of patent infringement could reasonably be asserted if a person not licensed by the owner of the patent engaged in the manufacture. use, or sale of the drug product. Declara?on Certi?cation 6.1 The undersigned declares that this is an accurate and complete submission of patent information for the NDA, amendment, or supplement pending under section 505 of the Federal Food, Drug, and Cosmetic Act. This time-sensitive patent information is submitted pursuant to 21 CFR 314.53. lattest that lam familiar with 21 CFR 314.53 and this submission complies with the requirements of the regulation. verify under penalty of perjury that the foregoing is true and correct. Warning: A willfully and knowingly false statement is a criminal offense under 18 0.3.6. 1001. 6.2 Authorized Signature of NBA Applicant/Holder or Patent Owner (Attorney. Agent, Representative or Date Signed other Authon?zed omen!) (Provide information below) 4/20/2013 NOTE: Only an NBA applicantlholder may submit this declaration directly to the FDA. A patent owner who Is not the NDA applicant] holder is authorized to sign the declaration but may not submit it directly to FDA. 21 CFR and (dual). Check applicable box and provide information below. NDA Applicanb'Hoider NDA Applicant'siHolder?s Attorney, Agent (Representative) or other Authorized Of?cial El Patent Owner Patent Owner's Attorney. Agent (Representative) or Other Authorized Of?cial Name Matthew A. Left; Director - Patents Address City/State Merck, PO. Box 2000, RY 86-2011A Rahway, NJ ZIP Code Telephone Number 070650907 732-594-1404 FAX Number (if available) I E-Mail Address (if available) 732-594-4720 The public reporting burden for this collection of information has been estimated to average 20 hours per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information. Send cements regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to: Food and Drug Administration CDER (RFD-007) 5600 Fishers Lane Rockville, MD 20857 An agency may not conduct or sponsor, and a person is no: required to respond to, a collection of information unless it displays a currentiy valid OMB control number. Substitute FORM FDA 35423 (312011) Page 3 Reference ID: 3501120 EXCLUSIVITY SUMMARY NDA # 205641 SUPPL # HFD # Trade Name: Asmanex HFA Inhalation Aerosol Generic Name: mometasone furoate Applicant Name: Merck Sharp and Dohme Corp. Approval Date, If Known: April 25, 2014 PART I IS AN EXCLUSIVITY DETERMINATION NEEDED? 1. An exclusivity determination will be made for all original applications, and all efficacy supplements. Complete PARTS II and III of this Exclusivity Summary only if you answer "yes" to one or more of the following questions about the submission. a) Is it a 505(b)(1), 505(b)(2) or efficacy supplement? YES NO If yes, what type? Specify 505(b)(1), 505(b)(2), SE1, SE2, SE3,SE4, SE5, SE6, SE7, SE8 505(b)(1) c) Did it require the review of clinical data other than to support a safety claim or change in labeling related to safety? (If it required review only of bioavailability or bioequivalence data, answer "no.") NO YES If your answer is "no" because you believe the study is a bioavailability study and, therefore, not eligible for exclusivity, EXPLAIN why it is a bioavailability study, including your reasons for disagreeing with any arguments made by the applicant that the study was not simply a bioavailability study. If it is a supplement requiring the review of clinical data but it is not an effectiveness supplement, describe the change or claim that is supported by the clinical data: Reference ID: 3495867 Page 1 d) Did the applicant request exclusivity? YES NO If the answer to (d) is "yes," how many years of exclusivity did the applicant request? e) Has pediatric exclusivity been granted for this Active Moiety? YES NO If the answer to the above question in YES, is this approval a result of the studies submitted in response to the Pediatric Written Request? IF YOU HAVE ANSWERED "NO" TO ALL OF THE ABOVE QUESTIONS, GO DIRECTLY TO THE SIGNATURE BLOCKS AT THE END OF THIS DOCUMENT. 2. Is this drug product or indication a DESI upgrade? YES NO IF THE ANSWER TO QUESTION 2 IS "YES," GO DIRECTLY TO THE SIGNATURE BLOCKS ON PAGE 8 (even if a study was required for the upgrade). PART II FIVE-YEAR EXCLUSIVITY FOR NEW CHEMICAL ENTITIES (Answer either #1 or #2 as appropriate) 1. Single active ingredient product. Has FDA previously approved under section 505 of the Act any drug product containing the same active moiety as the drug under consideration? Answer "yes" if the active moiety (including other esterified forms, salts, complexes, chelates or clathrates) has been previously approved, but this particular form of the active moiety, e.g., this particular ester or salt (including salts with hydrogen or coordination bonding) or other non-covalent derivative (such as a complex, chelate, or clathrate) has not been approved. Answer "no" if the compound requires metabolic conversion (other than deesterification of an esterified form of the drug) to produce an already approved active moiety. YES NO If "yes," identify the approved drug product(s) containing the active moiety, and, if known, the NDA #(s). Reference ID: 3495867 Page 2 NDA# 021067 22518 Asmanex Twisthaler Dulera MDI NDA# 019543 019625 019796 Elocon Ointment Elocon Cream Elocon Lotion NDA# 020762 Nasonex Nasal Spray 2. Combination product. If the product contains more than one active moiety(as defined in Part II, #1), has FDA previously approved an application under section 505 containing any one of the active moieties in the drug product? If, for example, the combination contains one never-before-approved active moiety and one previously approved active moiety, answer "yes." (An active moiety that is marketed under an OTC monograph, but that was never approved under an NDA, is considered not previously approved.) NO YES If "yes," identify the approved drug product(s) containing the active moiety, and, if known, the NDA #(s). NDA# NDA# NDA# IF THE ANSWER TO QUESTION 1 OR 2 UNDER PART II IS "NO," GO DIRECTLY TO THE SIGNATURE BLOCKS ON PAGE 8. (Caution: The questions in part II of the summary should only be answered “NO” for original approvals of new molecular entities.) IF “YES,” GO TO PART III. PART III THREE-YEAR EXCLUSIVITY FOR NDAs AND SUPPLEMENTS To qualify for three years of exclusivity, an application or supplement must contain "reports of new clinical investigations (other than bioavailability studies) essential to the approval of the application and conducted or sponsored by the applicant." This section should be completed only if the answer to PART II, Question 1 or 2 was "yes." 1. Does the application contain reports of clinical investigations? (The Agency interprets "clinical Reference ID: 3495867 Page 3 investigations" to mean investigations conducted on humans other than bioavailability studies.) If the application contains clinical investigations only by virtue of a right of reference to clinical investigations in another application, answer "yes," then skip to question 3(a). If the answer to 3(a) is "yes" for any investigation referred to in another application, do not complete remainder of summary for that investigation YES NO IF "NO," GO DIRECTLY TO THE SIGNATURE BLOCKS ON PAGE 8. 2. A clinical investigation is "essential to the approval" if the Agency could not have approved the application or supplement without relying on that investigation. Thus, the investigation is not essential to the approval if 1) no clinical investigation is necessary to support the supplement or application in light of previously approved applications (i.e., information other than clinical trials, such as bioavailability data, would be sufficient to provide a basis for approval as an ANDA or 505(b)(2) application because of what is already known about a previously approved product), or 2) there are published reports of studies (other than those conducted or sponsored by the applicant) or other publicly available data that independently would have been sufficient to support approval of the application, without reference to the clinical investigation submitted in the application. (a) In light of previously approved applications, is a clinical investigation (either conducted by the applicant or available from some other source, including the published literature) necessary to support approval of the application or supplement? YES NO If "no," state the basis for your conclusion that a clinical trial is not necessary for approval AND GO DIRECTLY TO SIGNATURE BLOCK ON PAGE 8: (b) Did the applicant submit a list of published studies relevant to the safety and effectiveness of this drug product and a statement that the publicly available data would not independently support approval of the application? YES NO (1) If the answer to 2(b) is "yes," do you personally know of any reason to disagree with the applicant's conclusion? If not applicable, answer NO. YES NO If yes, explain: (2) If the answer to 2(b) is "no," are you aware of published studies not conducted or sponsored by the applicant or other publicly available data that could independently Reference ID: 3495867 Page 4 demonstrate the safety and effectiveness of this drug product? YES NO X If yes, explain: (c) If the answers to (b)(1) and (b)(2) were both "no," identify the clinical investigations submitted in the application that are essential to the approval: P04334 P04431 Studies comparing two products with the same ingredient(s) are considered to be bioavailability studies for the purpose of this section. 3. In addition to being essential, investigations must be "new" to support exclusivity. The agency interprets "new clinical investigation" to mean an investigation that 1) has not been relied on by the agency to demonstrate the effectiveness of a previously approved drug for any indication and 2) does not duplicate the results of another investigation that was relied on by the agency to demonstrate the effectiveness of a previously approved drug product, i.e., does not redemonstrate something the agency considers to have been demonstrated in an already approved application. a) For each investigation identified as "essential to the approval," has the investigation been relied on by the agency to demonstrate the effectiveness of a previously approved drug product? (If the investigation was relied on only to support the safety of a previously approved drug, answer "no.") Investigation #1 YES NO Investigation #2 YES NO If you have answered "yes" for one or more investigations, identify each such investigation and the NDA in which each was relied upon: Two pivotal studies P04334 and P04431were submitted for NDA 22518 Dulera Inhalation Aerosol. Dulera consists of two active moieties, mometasone furoate and formoterol fumarate. The data for the individual components were not reviewed for efficacy in the review of the combination product. The two efficacy studies listed here P04334 and P0443 were reviewed again to support the efficacy of the single active moiety, mometasone furoate for the prophylaxis treatment of asthma. b) For each investigation identified as "essential to the approval", does the investigation Reference ID: 3495867 Page 5 duplicate the results of another investigation that was relied on by the agency to support the effectiveness of a previously approved drug product? Investigation #1 YES NO Investigation #2 YES NO If you have answered "yes" for one or more investigation, identify the NDA in which a similar investigation was relied on: c) If the answers to 3(a) and 3(b) are no, identify each "new" investigation in the application or supplement that is essential to the approval (i.e., the investigations listed in #2(c), less any that are not "new"): 4. To be eligible for exclusivity, a new investigation that is essential to approval must also have been conducted or sponsored by the applicant. An investigation was "conducted or sponsored by" the applicant if, before or during the conduct of the investigation, 1) the applicant was the sponsor of the IND named in the form FDA 1571 filed with the Agency, or 2) the applicant (or its predecessor in interest) provided substantial support for the study. Ordinarily, substantial support will mean providing 50 percent or more of the cost of the study. a) For each investigation identified in response to question 3(c): if the investigation was carried out under an IND, was the applicant identified on the FDA 1571 as the sponsor? Investigation #1 IND # YES ! ! ! NO ! Explain: Investigation #2 IND # Reference ID: 3495867 YES ! ! ! NO ! Explain: Page 6 (b) For each investigation not carried out under an IND or for which the applicant was not identified as the sponsor, did the applicant certify that it or the applicant's predecessor in interest provided substantial support for the study? Investigation #1 YES Explain: Investigation #2 YES Explain: ! ! ! NO ! Explain: ! ! ! NO ! Explain: (c) Notwithstanding an answer of "yes" to (a) or (b), are there other reasons to believe that the applicant should not be credited with having "conducted or sponsored" the study? (Purchased studies may not be used as the basis for exclusivity. However, if all rights to the drug are purchased (not just studies on the drug), the applicant may be considered to have sponsored or conducted the studies sponsored or conducted by its predecessor in interest.) YES NO X If yes, explain: ================================================================= Name of person completing form: Jessica Lee, Pharm.D. Title: Regulatory Health Project Manager Date: April 25, 2014 Name of Office/Division Director signing form: Lydia Gilbert-McClain, M.D. Title: Deputy Director Reference ID: 3495867 Page 7 Form OGD-011347; Revised 05/10/2004; formatted 2/15/05; removed hidden data 8/22/12 Reference ID: 3495867 Page 8 --------------------------------------------------------------------------------------------------------This is a representation of an electronic record that was signed electronically and this page is the manifestation of the electronic signature. --------------------------------------------------------------------------------------------------------/s/ ---------------------------------------------------JESSICA K LEE 04/25/2014 LYDIA I GILBERT MCCLAIN 04/25/2014 Reference ID: 3495867 MK-0887 MF PAGE I MODULE 1 1.3.3 DEBARMENT CERTIFICATION The applicant cited on the Form FDA 356h included with this submission hereby certi?es that it did not and will not use in any capacity the services of any person debarred under Section 306 of the Federal Food, Drug, and Cosmetic Act in connection with this application. a ?Pl. C2 0 /5 Elinor Chen, Date Director Worldwide Regulatory Affairs 0 Con?dential Reference ID: 3501120 NDA 205641 ACTION PACKAGE CHECKLIST APPLICATION NDA 205641 NDA Supplement If NDA. Ef?cacy Supplement Type: BLA BLA Supplement (an action package is not required for SE8 or SE9 supplements) Proprietary Name: Asmanex HFA Established/Proper Name: mometasone furoate Dosage Form: metered dose inhaler Applicant: Merck Sharp Dohme Corp. Agent for Applicant (if applicable): RPM: Division: For ALL 505 rior to EVERY action: NDA Application Type: 505(b)(l) 505(b)(2) Ef?cacy supplement: 50503)?) 5050))(2) 0 Review the information in the 505(b)(2) Assessment and submit the draft? to CDER 0ND 10 for clearance. BLA Application Type: El 3510?) El 351(3) 0 Check Orange Book for newly listed patents and/or Ef?cacy Supplement El 3510?) El 351(a) exclusivity (including pediatric exclusivity) El No changes New patent/exclusivity (noti?? CDER 0ND 10) Date of check: Note: If pediatric exclusivity has been granted or the pediatric information in the labeling of the listed drug changed, determine whether pediatric information needs to be added to or deleted from the labeling of this drug. 03? Actions 0 Proposed action . AP TA CR 0 User Fee Goal Date is 4/27/14 El El 0 Previous actions (speci?r tipe and date for each action taken) None If accelerated approval or approval based on ef?cacy studies in animals. were promotional materials received? Note: Promotional materials to be used within 120 days after approval must have been submitted (for exceptions. see If not submitted. explain Received Application Characteristics 3 1 The Application Information Section is (only) a checklist. The Contents of Action Package Section (beginning on page 2) lists the doc1unents to be included in the Action Package. 2 For resubmissions. applications must be cleared before the action. but it is not necessary to resubmit the draft 505(b)(2) Assessment to CDER 0ND 10 unless the Assessment has been substantively revised new listed drug. patent certi?cation revised). 3 Answer all questions in all sections in relation to the pending application. if the pending application is an NDA or BLA supplement. then the questions should be answered in relation to that supplement. not in relation to the original NDA or BLA. For example. if the application is a pending BLA supplement. then a new RMS-BLA Product Infonnation Sheet for TBP must be completed. Version: 2/ 7/2014 Reference ID: 3496120 Page 2 Review priority: Standard Priority Chemical classi?cation (new NDAs only): (con?rm chemical classi?cation at time of approval) El Fast Track full switch El Rolling Review partial switch El Orphan drug designation Direct-to-OTC Breakthrou Thera desi lation PY g1 NDAs: Subpart BLAs: Subpart Accelerated approval (21 CFR 314.510) El Accelerated approval (21 CFR 601.41) Restricted distribution (21 CFR 314.520) Restricted distribution (21 CFR 601.42) Subpait I Subpart Approval based on animal studies El Approval based on animal studies El Submitted in response to a PMR REMS: MedGuide El Submitted in response to a PMC Communication Plan Submitted in response to a Pediatric Written Request ETASU El MedGuide w/o REMS REMS not uired eq Comments BLAs only: Ensure Product Information Sheet for BP and RMS-BLA acilitv Information Sheet for BP have been completed and forwarded to (Vicky Yes. dates Carter) BLAs only: Is the product subject to of?cial FDA lot release per 21 CFR 610.2 Yes No (approvals only) Public conmmnications (approvals only) 0 Of?ce of Executive Programs (OEP) liaison has been noti?ed of action Yes No None FDA Press Release El FDA Talk Paper CDER El Other 0 Indicate what types (if any) of information were issued Exclusivity 0 Is approval of this application blocked by any type of exclusivity (orphan. 5-year NCE. 3-year. pediatric exclusivity)? No Yes 0 If so. specify the type Patent Information (NDAs only) 0 Patent Information: Verify that form FDA-3 542a was submitted for patents that claim the drug for which approval is sought. Veri?ed Not applicable because drug is an old antibiotic. CONTENTS OF ACTION PACKAGE Of?cer/Employee List List of of?cers/employees who participated in the decision to approve this application and consented to be identified on this list (approvals only) Ineluded Documentation of consent/non-consent by of?cers/ employees Included Version: 2/7/2014 Reference ID: 3496120 Page 3 Action Letters Copies of all action letters (including approval letter with ?nal labeling) Action(s) and date(s) AP 4/25/14 Labeling Package Insert (write submission/communication date at upper right of ?rst page of PI) 0 Most recent draft labeling (if it is division-proposed labeling, it should be in track-changes format) Included 0 Original applicant-proposed labeling Included Medication Guide/Patient Package h15e11/h15tructions for Use/Device Labeling (write submission/communication date at upper right of ?rst page of each piece) Medication Guide Patient Package Insert Instructions for Use Device Labeling None 0 Most-recent draft labeling (if it is division?proposed labeling, it should be in track-changes format) Included 0 Original applicant-proposed labeling Included Labels (full color carton and immediate-container labels) (write submission/communication date on upper right of ?rst page of each submission) 0 Most-recent draft labeling Included Proprietary Name 0 letter(s) (indicate date(s)) 0 Review(s) (indicate date(s) 12/6/13 12/1/13 Labeling reviews (indicate dates of reviews) RPM: None 9/3/13 DMEPA: None 2/25/14 (DRISK): El None 2/19/14: 3/24/14 OPDP: None 3/21/14 SEALD: None 4/14/14 CSS: None Other: None Administrative Regulatory Documents Administrative Reviews RPM Filing of Filing Meeting) (indicate date of each review) All NDA Actions: Date each action cleared by Clearance Committee 9/3/13 Not a NDAs only: Exclusivity Summary (signed by Division Director) Included 6? Application Integrity Policy (AIP) Status and Related Documents http://wvm? 0 Applicant Filing reviews for scienti?c disciplines should be ?led with the respective discipline. Reference ID: 3496120 Version: 2/7/2014 Page 4 0 This application is on the AIP If yes. Center Director?s Exception for Review memo (indicate date) 0 If yes. OC clearance for approval (indicate date of clearance communication) Yes No Not an AP action Pediatrics (approvals only) 0 Date reviewed by 1/1 5/ 14 If review not necessary. explain: Outgoing conmnmications: letters. emails. and faxes considered important to include in the action package by the reviewing of?ce/division clinical SPA letters) (do not include previous action letters, as these are located elsewhere in package) 7/9/13: 9/6/13; 3/27/14: 4/10/14: 4/11/1414/16/14: 4/18/14 Internal documents: memoranda. telecons. emails. and other documents considered important to include in the action package by the reviewing of?ce/division Regulatory Brie?ng minutes. Medical Policy Council meeting minutes) Minutes of Meetings 0 If not the ?rst review cycle. any end-of-review meeting (indicate date of mtg) or no 0 meeting (indicate date of mtg) No 9/9/11; 9/14/11 0 EOPZ meeting (indicate date of mtg) No 0 Mid-cycle Conmiunication (indicate date of mtg) 0 Late-cycle Meeting (indicate date of mtg) El 0 Other milestone meetings CMC pilots) (indicate dates of mtgs) Advisory Committee Meeting(s) No AC meeting 0 Date(s) of Meeting(s) Decisional and Summary Memos Of?ce Director Decisional Memo (indicate date for each review) None Division Director Summary Review (indicate date for each review) None 4/25/14 Cross-Discipline Team Leader Review (indicate date for each review) None 4/4/ 14 Development Templates (indicate total number) None 4/22/14 (3) Clinical Clinical Reviews 0 Clinical Team Leader Review(s) (indicate date for each review) No separate review see CDTL Review 0 Clinical review(s) (indicate date for each review) 8/22/13: 3/21/14 0 Social scientist review(s) (if OTC drug) (indicate date for each review) None Financial Disclosure reviews(s) or location/date if addressed in another review OR If no ?nancial disclosure information was required. check here and include a review/memo explaining why not (indicate date of review/memo) 3/21/14 Clinical Primary Review 4/22/14 Clinical reviews from inmmnology and other clinical areas/divisions/Centers (indicate date of each review) None Controlled Substance Staff review(s) and Scheduling Recommendation (indicate date of each review) Reference ID: 3496120 Version: 2/7/2014 Page 5 .0 Risk Management 0 REMS Docrmlents and REMS Supporting Document (indicate date(s) of submission(s)) 0 REMS Memo(s) and letter(s) (indicate datels)) 0 Risk management review(s) and recommendations (including those by OSE and CSS) (indicate date of each review and indicate location/date if incorporated into another review) None 081 Clinical Inspection Review (include copies of 051 letters to investigators) None requested Clinical Microbiology None Clinical Microbiology Team Leader Review(s) (indicate date for each review) El No separate review Clinical Microbiology Review(s) (indicate date for each review) None El None Biostatistics Statistical Division Director Review(s) (indicate date for each review) Statistical Team Leader Review(s) (indicate date for each review) No separate review No separate review Statistical Review(s) (indicate date for each review) None 8/28/13: 3/20/14 El None Clinical Pharmacology Clinical Pharmacology Division Director Review(s) (indicate date for each review) No separate review Clinical Phannacology Team Leader Review(s) (indicate date for each review) No separate review Clinical Pharmacology review(s) (indicate date for each review) None 8/20/13: 3/14/14 081 Clinical Pharmacology Inspection Review Summary (include copies of letters) None requested Nonclinical None PllammcologyfToxicology Discipline Reviews 0 Review(s) (indicate date for each review) No separate review 0 Supervisory Review(s) (indicate date for each review) No separate review 0 Pharm/tox review(s). including referenced IND reviews (indicate date for each review) None 8/9/13: 3/7/14 Review(s) by other disciplines/divisions/Centers requested by reviewer (indicate date for each review) None Statistical review(s) of carcinogenicity studies (indicate date for each review) No care report/memo of meeting None Included in PIT review. page OSI Nonclinical Inspection Review Simnnary (include copies of 051 letters) None requested Reference ID: 3496120 Version: 2/7/2014 Page 6 Product Quality El None Product Quality Discipline Reviews 0 Division Director Review(s) (indicate date for each review) No separate review 0 Branch Chief/Team Leader Review(s) (indicate date for each review) No separate review 3/ 18/14 0 Product quality review(s) including ONDQA biopharmaceutics reviews (indicate None 7/24/13: 3/18/14: date for each review) 4/23/14 Microbiology Reviews Not needed NDAs: Microbiology reviews (sterility pyrogenicity) (indicate 7/22/13 date of each review) El BLAs: Sterility assurance. microbiology. facilities reviews (indicate date of each review) Reviews by other disciplines/divisions/ Centers requested by quality reviewer (indicate date of each review) None EnvironmentalAssessment (check one) (original and supplemental applications) Categorical Exclusion (indicate review date)(all original applications and . . . 3/ 1 8/ 4 all e?icacv supplements that could increase the patient population) Review FONSI (indicate date of review) Review Enviromnental Impact Statement (indicate date of each review) Facilities Review/Inspection El NDAs: Facilities inspections (include EER printout or EER Summary Report Date completed: 8/6/2013 only; do NOT include EER Detailed Report: date completed must be within 2 Acceptable years of action date) (onlv original NDAs and supplements that include a new Withhold recommendation facilitv or a change that a?ects the manufacturing sites5) Not applicable Date completed: El BLAs: TB-EER (date of most recent TB-EER must be within 30 days of action date) (original and supplemental BLAs) El Acceptable Withhold Completed [3 Requested El Not yet requested Not needed (per review) NDAs: Methods Validation (check box only, do not include documents) 5 a new facility or a change in the facility. or a change in the manufacturing process in a way that impacts the Quality Management Systems of the facility. Version: 2/7/2014 Reference ID: 3496120 Page 7 Day of Approval Activities - - No chan es 0:0 For all 505(b)(2) applications: . . . 0 Check Orange Book for newly listed patents and/or exclusivity (including El Ne? (Norm . . . . CDER 0ND 10) pediatric 0 Finalize 505(b)(2) assessment El Done Send a courtesy copy of approval letter and all attachments to applicant by fax or secure Done email 6? If an FDA communication will issue. notify Press Of?ce of approval action after Done con?rming that applicant received coru'tesy copy of approval letter oto Ensure that proprietary name, if any. and established name are listed in the Application Product Names section of DARRTS. and that the proprietary name is one identi?ed as the ?preferred? name 0:0 Ensure Pediatric Record is accurate El Done ~20 Send approval email within one business day to El Done Version: 2/7/2014 Reference ID: 3496120 --------------------------------------------------------------------------------------------------------This is a representation of an electronic record that was signed electronically and this page is the manifestation of the electronic signature. --------------------------------------------------------------------------------------------------------/s/ ---------------------------------------------------JESSICA K LEE 04/25/2014 Reference ID: 3496120 NDA 205641 Asmanex HFA Your submission dated June 27, 2013, to NDA 205641, is currently under review. We request that you send your agreement to the following comments: 1. Update your post-approval long term ongoing stability study protocol to specify the storage orientation (valve up, down, or horizontal). 2. As required under 21 CFR 314.81(b)(1)(ii), commit to immediately discuss with the Agency any aberrations of the drug product from its approved specifications and to withdraw the affected lots from the market as warranted. We request for your agreements and the projected date of submission for the requested information by close of business, Monday, April 21, 2014. The information can be sent by electronic mail to Jessica.Lee@fda.hhs.gov, followed by an official submission to the NDA. If you have any questions, please contact Jessica Lee, Regulatory Project Manager, at 301-7963769. Reference ID: 3492256 NDA 205641 Asmanex HFA Drafted by: JLee/4.18.14 Initialed by: LJafari/4.18.14 PPeri/4.18.14 Finalized by: JLee/4.18.14 Reference ID: 3492256 --------------------------------------------------------------------------------------------------------This is a representation of an electronic record that was signed electronically and this page is the manifestation of the electronic signature. --------------------------------------------------------------------------------------------------------/s/ ---------------------------------------------------JESSICA K LEE 04/18/2014 Reference ID: 3492256 NDA 205641 Asmanex HFA Dear Mr. Hambaugh: Your NDA submission dated June 27, 2013, is currently under review. We ask that you address the following. We have also attached the revised patient information leaflet and instructions for use. Please note insertions are underlined and deletions are strike out. Be advised that these labeling changes are not necessarily the Agency’s final recommendations and that additional labeling changes may be forthcoming as the label is continued to be reviewed.  Highlights (HL) must be in a minimum of 8 point font and should be in two-column format, with ½ inch margins on all sides and between columns. The top margin is > 1/2 inch in Highlights.  The 4-digit year is missing and should state: "2014" for the Initial U.S. Approval in Highlights.  The Revision Date in Highlights is missing and should state: "4/2014".  There is excess white space between Table of Contents (TOC) and the horizontal line above Full Prescribing Information (FPI). For improved readability, consider deleting this excess white space.  For improved readability, use bullets when there is more than one item (e.g., piece of information) under each heading in HL. Add bullets under Dosage &Administration.  In Section 17, we recommend that information is organized by subsection headings or bullets (not subsection numbers). We recommend removing the subsection numbers and subheadings; this will also affect TOC. Use of command language is also recommended; see the draft Patient Counseling Information section guidance and the Labeling Review Tool. Submit a clean copy and a tracked-change version of the label incorporating our recommended changes to the NDA by close of business Friday, April 18, 2014. In addition, please send a copy of the revised label via email to Jessica.Lee@fda.hhs.gov. If you have any questions, please contact Jessica Lee, Regulatory Project Manager, at 301-7963769. Reference ID: 3490692 NDA 205641 Asmanex HFA Drafted by: Cleared by: NTon/April 15, 2014 LJafari/April 15, 2014 KWitzmann/April 16, 2014 Finalized by: JLee/April 16, 2014 9 Page(s) of Draft Labeling have been Withheld in Full as b4 (CCI/TS) immediately following this page Reference ID: 3490692 --------------------------------------------------------------------------------------------------------This is a representation of an electronic record that was signed electronically and this page is the manifestation of the electronic signature. --------------------------------------------------------------------------------------------------------/s/ ---------------------------------------------------JESSICA K LEE 04/16/2014 Reference ID: 3490692 NDA 205641 Asmanex HFA Your submission dated June 27, 2013, to NDA 205641, is currently under review. We also refer to your submission dated April 4, 2014. We have the following comments. We have also attached the revised package insert and patient information lea?et. Please note insertions are underlined and deletions are strike out. Please note that these comments are not the Agency?s ?nal comments and that we may have additional labeling recommendations as we continue to review your application. In general, we agree with your chan es, as noted in the revised draft labelin documents submitted on A ril 4, 2014. We request you address the de?ciencies and submit a corrected label by close of business, Wednesday, April 16, 2014. The information can be sent by electronic mail to Jessica.Lee@fda.hhs.gov, followed by an of?cial submission to the NDA. If you have any questions, please contact Jessica Lee, Regulatory Project Manager, at 301-796-3 769. Reference ID: 3488256 --------------------------------------------------------------------------------------------------------This is a representation of an electronic record that was signed electronically and this page is the manifestation of the electronic signature. --------------------------------------------------------------------------------------------------------/s/ ---------------------------------------------------JESSICA K LEE 04/11/2014 Reference ID: 3488256 NDA 205641 Asmanex HFA We are reviewing your NDA submission dated June 27, 2013, and the Pediatric Plan dated September 4, 2013. You propose to conduct pediatric studies in patients 5 through 11 years of age. We request that you submit your commitment to conduct these pediatric studies and provide the dates for Final Protocol Submission, Study Completion, and Final Report Submission for each of the studies listed below: A 12-week, randomized, placebo-controlled, dose-ranging efficacy and safety study of mometasone furoate metered dose inhaler (MDI) in the treatment of children ages 5-11 years with persistent asthma. Protocol Submission: Study Completion: Final Report Submission: A 12-week, double-blind, active-controlled, efficacy and safety study of two doses of mometasone furoate/formoterol fumarate combination MDI compared with the corresponding doses of mometasone furoate monotherapy MDI in the treatment of children ages 5-11 with persistent asthma. Protocol Submission: Study Completion: Final Report Submission: A 6-month safety study, with a 6-month extension of two doses of mometasone furoate/formoterol fumarate combination MDI compared to fluticasone/salmeterol combination DPI in children 5-11 years of age with persistent asthma. Protocol Submission: Study Completion: Final Report Submission: Provide your response by Close of Business, Wednesday, April 16, 2014. The information can be sent by electronic mail to Jessica.Lee@fda.hhs.gov, followed by an official submission to the NDA. If you have any questions, please contact Jessica Lee, Regulatory Project Manager, at 301-796-3769. Reference ID: 3487308 NDA 205641 Asmanex HFA Drafted by: JLee/4.8.14 Initialed by: LJafari/4.8.14 ADurmowicz/4.9.14 SSeymour/4.9.14 Finalized by: JLee/4.10.14 Reference ID: 3487308 --------------------------------------------------------------------------------------------------------This is a representation of an electronic record that was signed electronically and this page is the manifestation of the electronic signature. --------------------------------------------------------------------------------------------------------/s/ ---------------------------------------------------JESSICA K LEE 04/10/2014 Reference ID: 3487308 NDA 205641 Asmanex HFA Your submission dated June 27, 2013, to NDA 205641, is currently under review. We have the following comments. Please note that these comments are not the Agency’s final comments and that we may have additional labeling recommendations as we continue to review your application. Package Insert (PI) Refer to the attached PI for recommended changes. Patient Package Insert (PPI) Refer to the attached PPI for comments and recommendations. Patient Instructions For Use (IFU) 1. Under the heading ‘Before you use Asmanex HFA for the first time, you must prime the inhaler,’ revise step one to read: ‘ To prime the inhaler, hold it in the upright position away from your face, and press down firmly and fully on the top of the canister until it stops moving in the actuator. Do this 4 times to release a total of 4 actuations (puffs) into the air.’ 2. Refer to the attached IFU for additional comments and recommendations. All Carton Labeling and Container Labels 1. Remove the line above the trade name and under the NDC number to increase readability. 2. Decrease the font size of the statement ‘Shake well before using’ as it competes for prominence with the proprietary name. 3. Unbold the ‘Rx only’ statement. We request you address the deficiencies and submit a corrected label by noon, Wednesday, April 2, 2014. If you have any questions, please contact Jessica Lee, Regulatory Project Manager, at 301-796-3769. 32 Page(s) of Draft Labeling have been Withheld in Full as b4 (CCI/TS) immediately following this page Reference ID: 3478921 NDA 205641 Asmanex HFA Drafted by: JLee/March 27, 2014 Initialed by: LJafari/March 27, 2014 Finalized by: JLee/March 27, 2014 Reference ID: 3478921 --------------------------------------------------------------------------------------------------------This is a representation of an electronic record that was signed electronically and this page is the manifestation of the electronic signature. --------------------------------------------------------------------------------------------------------/s/ ---------------------------------------------------JESSICA K LEE 03/27/2014 Reference ID: 3478921 PeRC PREA Subcommittee Meeting Minutes January 15, 2014 PeRC Members Attending: Lynne Yao Rosemary Addy Hari Cheryl Sachs George Greeley Robert “Skip” Nelson Jane Inglese Wiley Chambers Tom Smith Karen Davis-Bruno Shrikant Pagay Lily Mulugeta Dianne Murphy William J. Rodriguez Kevin Krudys Maura O’Leary Daiva Shetty Coleen LoCicero Peter Starke (b) (4) (b) (4) Agenda PREA 10:55 NDA (b) (4) Asmanex HFA (Partial Waiver/Deferral/Plan) Maintenance treatment of asthma as a prophylactic therapy in patients 12 years of age and older (b) (4) Reference ID: 3446429 Asmanex HFA Partial Waiver/Deferral/Plan/Appropriately Labeled • NDA 205641 seeks marketing approval for Asmanex HFA for the maintenance treatment of asthma as prophylactic therapy in patients 12 years of age and older. • The application has a PDUFA goal date of April 27, 2014. • The application triggers PREA as directed to a new dosing regimen. • PeRC Recommendations: o The PeRC agreed with the Division to grant a partial waiver in patients less than five years of age because the product fails to offer a meaningful therapeutic benefit and a deferral studies in patients 5 to 11 years because studies are underway. The product is appropriately labeled for use in patients 12 years of age and older. o (b) (4) (b) (4) Reference ID: 3446429 Reference ID: 3446429 --------------------------------------------------------------------------------------------------------This is a representation of an electronic record that was signed electronically and this page is the manifestation of the electronic signature. --------------------------------------------------------------------------------------------------------/s/ ---------------------------------------------------GEORGE E GREELEY 02/03/2014 Reference ID: 3446429 DEPARTMENT OF HEALTH & HUMAN SERVICES Food and Drug Administration Silver Spring, MD 20993 NDA 205641 PROPRIETARY NAME REQUEST CONDITIONALLY ACCEPTABLE Merck Sharp & Dohme Corp. 126 E. Lincoln Avenue P.O. Box 2000 RY33-212 Rahway, NJ 07065-0900 Attention: Elinor Chen, Ph.D. Director, Worldwide Regulatory Affairs Dear Dr. Chen: Please refer to your New Drug Application (NDA) dated June 26, 2013, received June 27, 2013, submitted under section 505(b)(1) of the Federal Food, Drug, and Cosmetic Act for Mometasone Furoate Inhalation Aerosol, 100 mcg and 200 mcg. We also refer to your September 12, 2013, correspondence, received September 12, 2013, requesting review of your proposed proprietary name, Asmanex HFA. We have completed our review of the proposed proprietary name, Asmanex HFA, and have concluded that it is acceptable. If any of the proposed product characteristics as stated in your September 12, 2013 submission are altered prior to approval of the marketing application, the proprietary name should be resubmitted for review. If you have any questions regarding the contents of this letter or any other aspects of the proprietary name review process, contact Nichelle Rashid, Safety Regulatory Project Manager in the Office of Surveillance and Epidemiology, at (301) 796-3904. For any other information regarding this application contact the Office of New Drugs (OND) Regulatory Project Manager, Jessica Lee, at (301) 796-3769. Sincerely, {See appended electronic signature page} Kellie A. Taylor, Pharm.D., MPH Deputy Director Office of Medication Error Prevention and Risk Management Office of Surveillance and Epidemiology Center for Drug Evaluation and Research Reference ID: 3417434 --------------------------------------------------------------------------------------------------------This is a representation of an electronic record that was signed electronically and this page is the manifestation of the electronic signature. --------------------------------------------------------------------------------------------------------/s/ ---------------------------------------------------KELLIE A TAYLOR 12/06/2013 Reference ID: 3417434 DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Silver Spring MD 20993 NDA 205641 FILING COMMUNICATION – NO FILING REVIEW ISSUES IDENTIFIED Merck Sharp & Dohme Corp. One Merck Drive P.O. Box 1000 Whitehouse Station, NJ 08889 Attention: Elinor Chen, PhD Director, Worldwide Regulatory Affairs Dear Dr. Chen: Please refer to your New Drug Application (NDA) dated June 26, 2013, received June 27, 2013, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act, for Asmanex HFA (mometasone furoate) 100 mcg and 200 mcg Inhalation Aerosol. We also refer to your amendment dated September 4, 2013. We have completed our filing review and have determined that your application is sufficiently complete to permit a substantive review. Therefore, in accordance with 21 CFR 314.101(a), this application is considered filed 60 days after the date we received your application. The review classification for this application is Standard. We are reviewing your application according to the processes described in the Guidance for Review Staff and Industry: Good Review Management Principles and Practices for PDUFA Products. Therefore, we have established internal review timelines as described in the guidance, which includes the timeframes for FDA internal milestone meetings (e.g., filing, planning, midcycle, team and wrap-up meetings). Please be aware that the timelines described in the guidance are flexible and subject to change based on workload and other potential review issues (e.g., submission of amendments). We will inform you of any necessary information requests or status updates following the milestone meetings or at other times, as needed, during the process. If major deficiencies are not identified during the review, we plan to communicate proposed labeling and, if necessary, any postmarketing commitment requests by March 30, 2014. We request that you submit the following information: 1. Provide the PK data sets acquired from study P04275 and P03658. 2. Submit a request for evaluation of your proprietary name, Asmanex HFA, for NDA 205641. Please refer to the guidance entitled: Guidance for Industry: Contents of a Reference ID: 3369158 NDA 205641 Page 2 Complete Submission for the Evaluation of Proprietary Name http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guid ances/UCM075068.pdf. Upon preliminary review of your submitted labeling, we have the following comment: During our review, we will be assessing the appropriateness of inclusion of data from a combination program in the labeling for a monotherapy product, as well as the applicability of data from older monotherapy studies. Please respond only to the above requests for information. While we anticipate that any response submitted in a timely manner will be reviewed during this review cycle, such review decisions will be made on a case-by-case basis at the time of receipt of the submission. We acknowledge your request for a waiver of the requirement that the Highlights of Prescribing Information be limited to no more than one-half page. We will consider your request during labeling discussions. In the meantime, we encourage you to submit revised labeling that meets the half page requirement. PROMOTIONAL MATERIAL You may request advisory comments on proposed introductory advertising and promotional labeling. Please submit, in triplicate, a detailed cover letter requesting advisory comments (list each proposed promotional piece in the cover letter along with the material type and material identification code, if applicable), the proposed promotional materials in draft or mock-up form with annotated references, and the proposed package insert (PI), and patient PI (as applicable). Submit consumer-directed, professional-directed, and television advertisement materials separately and send each submission to: Food and Drug Administration Center for Drug Evaluation and Research Office of Prescription Drug Promotion (OPDP) 5901-B Ammendale Road Beltsville, MD 20705-1266 Do not submit launch materials until you have received our proposed revisions to the package insert (PI), and patient PI (as applicable), and you believe the labeling is close to the final version. For more information regarding OPDP submissions, please see http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm. If you have any questions, call OPDP at 301-796-1200. REQUIRED PEDIATRIC ASSESSMENTS Reference ID: 3369158 NDA 205641 Page 3 Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for new active ingredients, new indications, new dosage forms, new dosing regimens, or new routes of administration are required to contain an assessment of the safety and effectiveness of the product for the claimed indication(s) in pediatric patients unless this requirement is waived, deferred, or inapplicable. Pediatric studies conducted under the terms of section 505B of the Federal Food, Drug, and Cosmetic Act (the Act) may also qualify for pediatric exclusivity under the terms of section 505A of the Act. If you wish to qualify for pediatric exclusivity please consult Division of Pulmonary, Allergy, and Rheumatology Products. Please note that satisfaction of the requirements in section 505B of the Act alone may not qualify you for pediatric exclusivity under 505A of the Act. We acknowledge receipt of your request for a partial waiver of pediatric studies for this application. Once we have reviewed your request, we will notify you if the partial waiver request is denied. We acknowledge receipt of your request for a partial deferral of pediatric studies for this application. Once we have reviewed your request, we will notify you if the partial deferral request is denied. If you have any questions, call Jessica Lee, Regulatory Project Manager, at (301) 796-3769. Sincerely, {See appended electronic signature page} Badrul A. Chowdhury, MD, PhD Director Division of Pulmonary, Allergy, and Rheumatology Products Office of Drug Evaluation II Center for Drug Evaluation and Research Reference ID: 3369158 --------------------------------------------------------------------------------------------------------This is a representation of an electronic record that was signed electronically and this page is the manifestation of the electronic signature. --------------------------------------------------------------------------------------------------------/s/ ---------------------------------------------------BADRUL A CHOWDHURY 09/06/2013 Reference ID: 3369158 US. Food and Drug Admhistra?m Prcutixrlir'g and Pnjmijlhg .fdagov NDA 205,641 Asmanex HFA (inhaled mometasone furoate) Merck Filing Meeting Kim Witzmann, MD Medical Officer Clinical Review August 07, 2013 Reference ID: 3361223 a US. Food and Drug Adm'nistra?lian Prolacnir-g and Pny'nothg PLtilic; Health Executive Summary - - ?Maintenance treatment of asthma as prophylactic therapy in patients 12 years of age and older? - Proposed Dose: 2 inhalations of 100mcg or 200mcg MF BID - Related Products: Dulera MDI(Mometasone Furoate/ Formoterol) 200/10 and 400/10mcg Asmanex Twisthaler (mometasone Furoate) DPI, 110 and 220mcg - Recommendation: Fileable - Key Review Issues to be discussed in Planning Discussion Labeling of efficacy data with older MF formulation 9/14/2011) No OSI Audit required (already done) No AC required Reference ID: 3361223 Briefly, the regulatory history for Mometasone Furoate for this Sponsor includes: Approval of the DPI formulation of mometasone (As Asmanex Twisthaler) in March 2005, And subsequent extension of indication down to 4yo for the DPI in 2008 Dulera HFA in two dose levels was approved in June, 2010, but the NDA for a COPD indication was given a Complete Response last year. In the Dulera approval letter, we requested that the Sponsor consider development of the HFA mometasone monotherapy- to which they agreed , and Pre-IND package was submitted in August 2011. Written pre-meting comments were sent in September, which confirmed that the Sponsor would not need additional studies to submit MF MDI for NDA, but raised two labeling issues, regarding support for the 400mcg dose, since there was no placebo, and with regard to supportive data from the Sponsor’s old MDI development program, which utilized a somewhat different MDI product than that created for the Dulera program. The meeting was cancelled. Reference ID: 3361223 3 I wanted to utilize today’s discussion to get more of a sense if we need to send any high-level comments to the Sponsor at this time. Primarily, a comment regarding labeling language,Additionally, contact Sponsor regarding need for PSP for the 5-11yo population, which will include the Dulera PSP (which is already evaluating the mometasone MDI component of that combination) Reference ID: 3361223 4 For Asmanex HFA, the Sponsor includes 17 studies in the clinical development program . The Studies beginning with the letter “P” utilized the to-be-marketed formulation of Mometasone Furoate HFA, and studies were performed in the mid-2000’s. All of these studies have been reviewed as part of the Dulera NDA, which utilized a full factorial design for the combination product. (The only exception is the Phase 4 bone mineral density study, P03418, which was completed during the Dulera review cycle, which used the DPI formulation.) Studies beginning with the letters “C” or “I” were from the original MDI program, and utilized a somewhat different formulation; these studies were conducted in the mid-1990’s, and completed in 1998-99. All but 4 of these studies, marked with an asteric, were also submitted as part of the Dulera NDA.. Reference ID: 3361223 5 With regard to efficacy, the Sponsor identifies 8 studies in support for the efficacy of Mometasone HFA, shown here in green. Studies P04334 and P04431 are identified as pivotal, and were the same pivotal trials used for Dulera. The remaining 6 studies identified by the Sponsor from the mometasone monotherapy program in the mid-’90s, which utilized the older formulation. These 6 primarily dose-findng, utilizing a series of endpoints to measure efficacy, or dose-frequency studies, exploring one daily morning or evening dosing versus twice daily dosing. They are, in general, supportive of the doses carried forward into the new formulation’s Dulera and Asmanex HFA programs, but due to the differences in product, we cannot draw upon these directly for demonstration of efficacy. Reference ID: 3361223 6 To briefly describe the PIVOTAL Study results, Study P04334 was a 26 week, R, DB, PC, full factorial study of MF/F, at 200/10mcg dose, compared to each of its individual components, as well as placebo. Previous review concluded that the 200mcg dose of MF demonstrated efficacy over placebo, as well as provided contribution to the efficacy of the combination, as shown in the graph on the left. Time to first exacerbation favored treatment with MF over placebo, and Secondary endpoints were all generally supportive as well. These results support the efficacy of MF 200 monotherapy. Study P04431 was a 12 week, R, DB study of partial factorial design, because of safety concern for placebo, or a LABA alone. It compared the MF/F combination 200/10 to the 400/10 dose, as well as to the 400 MF monotherapy. The co-primary efficacy endpoint of mean AUC0-12hr of change from baseline to week 12 was intended to assess the LABA contribution of the combination, comparing MF/F 400/10 to the 400mcg monotherapy, which demonstrated efficacy of the Formoterol component. The key secondary endpoint of trough FEV1 at week 12 also demonstrated a numerical increase in mean change of the 400/10 dose compared to the 200/10 group, with a treatment difference of 0.05L (p= 0.145). Together, these provide justification for the additional benefit of the 400mcg dose over the 200mcg dose in severe asthmatic patients, given that the effect of the formoterol 10mcg component would be expected to exert the same effect in both dose cohorts. Secondary endpoints including onset of action, AQLQ, ACQ, nocturnal awakenings, peak flow, time-toexacerbation, and rescue medication use also provided support for efficacy. Reference ID: 3361223 7 In evaluation of safety, The Sponsor identifies an additional 8 studies in support for the safety of MF HFA, shown here in purple. Studies P04334 and P04431 are again identified as pivotal, same pivotal trials used for Dulera, data was pooled for the two studies. The Sponsor groups the findings from the remaining studies in the Summary of Clinical Safety, based on study design, so for example, studies C97-225, -226, and -227 are pooled, as 12wk placebo controlled trials. Studies C97-223 and -224 were 3month PC studies with 9mo long-term safety data collected, so are grouped together, likewise, I97-200 and P04705 are grouped. The others are reported singly. Also of safety note, P03705 was the HPA axis study, P03418 was the bone mineral density study P04703 was the open-label dose counter study P03658 and P05644 were Phase 1 PK studies that the Sponsor identified as important for safety, and were reviewed in Dulera. Reference ID: 3361223 8 Because the submitted trials differ somewhat from the Dulera program, I looked briefly at patient exposure to mometasone for the HFA and older MDA formulation. Overall, 4015 patients 12 years and older were exposed to at least one dose of mometasone, With doses from 50mcg once daily to 800mcg BID for monotherapy, or the combination product 110/10 to 400/10 BID for as long as 52 weeks A bit more than half of the patients received the approved formulation of MF/F HFA, or the equivalent HFA mometasone monotherapy Slightly less than half were from studies conducted in the mid-’90s with the older MDI formulation. Again, 4 of these studies, -222, -223, -226, and -227, were not reviewed in the Dulera NDA, which accounted for 1158 of the 1800 patients. Reference ID: 3361223 9 With regard to major safety events, Here I have briefly highlighted events seen in the pivotal trials or previously reviewed Dulera program, as compared to events that occurred in the older MDI studies not previously submitted. As you can see, there were 5 total deaths; 2 from pivotal studies already reviewed, one in the bone mineral density study, and 2 others from C97-224 Withdrawals due to AEs , as well as AE and SAE s are noted here. There do not appear to be any significant safety differences between the older and newer formulations of mometasone, but one aspect of my review will be to make sure there are no unusual events ,or higher frequencies of events, in those studies not previously reviewed. Even if there are differences in the older program safety, it’s unlikely this would significantly change anything, because these are all from the older formulation. I think we can rely on the old program safety as supportive since exposure was the same or slightly higher with the old formulation (Reference to Craig’s graphs and Sponsor’s submission 5/26/2010, comparing old and new). Reference ID: 3361223 10 [m 1 wirl Filing Meeting: FILEABLE 0 Clinical Filing Checklist completed, no omissions noted 505(b)(1) - Pediatric Development Plan: PMR for Dulera, waivers - OSI Audits- completed under the Dulera review Pediatric Partial Waiver Partial waiver requested for 5-11vo; due to pediatric studies for Dulera required by PREA, ongoing and planned P04223- 12wk, R, PC, dose range/efficacy/safety (W4) MF 50mcg BID, 100 BID, ZOOBID, (W4) placebo 12wk, DB, AC efficacy and safety I Ml: (hm) 6month, LT safety w/ 6 mo extension of vs. fluticasone /sa metero --Do they need to provide PSP, not waiver, for this data? Partial waiver was granted for Dulera for children 4 years and youngerI based on LABA safety concerns, and available therapeutic alternatives THEREFORE that waiver precludes the need to provide step-down from Dulera, so 21CFR 314.55 "Product does not represent meaningful therapeutic benefit over existing therapies and is unlikely to be used in a substantial number of pediatric pts.? --Appears reasonable Reference ID: 3361223 1 1 Planning for Asmanex HFA Review Issues: - Demonstrated Efficacy and Safety already - Consults- Standard - Advisory Committee-not required - Label Administrative lssues- how to translate data from a combination program into a label for the monotherapy Review issues are described here: One point which make this application different from most others is that the efficacy and safety have already been demonstrated as part of the factorial design within the DULERA program Standard consults are needed, and have been sent; OSE not required, as inspections were already completed under the DULERA program AC not required, since this is a and no New Indication is being requested Majority of issues will be regarding labeling, and how to translate the data from a combination program into a label for monotherapy. The Sponsor?s approach in the submitted label was to use the DULERA label, and remove LABA-specific statements. In addition, they used the ASMANEX TWISTHALER for the INDICATION. I will describe a bit more on the next slide 1 Page of Draft Labeling has been Withheld in Full as b4 immediately following this page Reference ID: 3361223 1 2 I wanted to utilize today’s discussion to get more of a sense if we need to send any high-level comments to the Sponsor at this time. Primarily, a comment regarding labeling language,Additionally, contact Sponsor regarding need for PSP for the 5-11yo population, which will include the Dulera PSP (which is already evaluating the mometasone MDI component of that combination) Reference ID: 3361223 14 a US. Food and Drug Admhistra?m and .fdagov Back up Slides Reference ID: 3361223 15 The Sponsor believes that the studies that were completed in the asthma program and in the original MF MDI program adequately characterize the ef?cacy and safety on MF monotherapy via MDI and that no additional clinical efficacy or safety studies will be required. Does the Agency agree? Referring to your response to Question 2, we understand the comment to be highlighting a potential labeling dif?culty rather than one of approvability of the 400mcg strength. Please confirm that this interpretation is correct. One possible approach to labeling would be to describe the change from baseline data with the to-be- marketed product and then discuss efficacy data at that close obtained with a similar MDI, with transparency regarding the conditions under which that data was collected. a US. Food and Drug Admhistra?m Preulectir-g and Pmlic Health Comments-02 mum Yes, we agree. However, we anticipate difficuity in describing efficacy information for the 400 dose ievei in the iabei, since none of the piacebo-controiied triais for the MF 400mcg dose ievei were performed with the to-be-rnarketed formulation. in addition. these piacebo?controiied triais did not assess FEW at a pre?specified time point in the dosing intervai, such as the trough. The response to Question 2 is in reference to iabeiing, not to approvabii'ity. it is premature to discuss specific iabeiing at this time. in generai. we note that inciusion of efficacy data using the cider mometasone furoate formuiation be probiematic. Pre-INDit 112,659 Meeting Package 5?26?1 1: F?re?mtg comment 9?09-1 1; Response to IR 9?14?11 Reference ID: 3361223 16 2.14.1 2.1.2 and Summary DI 80m. Adv-In Evmls Durlng In. Trommom Period - Pool-a Plvoul Studies MJI MF IIDI "06 BID "Cr; BIC HOG BID MCC- BID MEG an 1W m255 n=I92 n=202 (DISORIIRS I In I :04AHMIINAL 9AM I II II I ID II LPFEII DIARRHOEA I: a I ILIEI .Gastan RFFI DISFASF IOAI I IOEI INFECIIDMS AND 3 7 II a [2NIFRI IIs INFLUENZA IBSCESEI VIRAL I II I: I IO IJ WISOMG IND FPOCEDUDJIL I (II 3 0 I I0 Muscu- 51mm DISORDERS 1N3 DONNECTIVE TISSUE DISORDEFB Mus-1E sums (I I 51 I PAIN IN MW I In SI I NERVOUS SISTEM DISORIJERS PEACHIQIE HI-AIIMZHE I I DISORDERS 1 ID 7) I DEPRESSION I ID 2) II 0 I RENAL URINAEYDISCIFDEFIS I (II-I: II 0 I ARIE av 515M515 I I HhsPIIqum. IHcmm ma mousrlm ulsmums 'ASTHMA TISSUE DISORDEFIS 0 3 I I Mom: a I I SURGICAL MEDICAL PROCEDURES I ID 5] I 2? SPINAL I I TOOTH WCTIDN II Reference ID: 3361223 .1251 p1? SAEs in Pivotal 17 Severe Asthma-related AE Table 12 0! Subjects Who Had Severe AsmmaRelatea Events Protocol N05. ?37-200. (397-222. (397-224. CST-203. P044151. P411705. 5304334 ma P041259 Sexmger' Sth'yr'CenlerJSubjecl Race? Adverse EvenlIs] 'r Seventy and Oulcume MF not 100 BID tar?zoman Aslrma aggravated Possrme? Severe. Hosptratrzea. :vc S-Mon??l Phase: MF Variable naso? ISM-224450069 Fr?27rc Aslnma aggravated Unttxely Severe. c97_224?om42 Frame Aslrma aggravated Unliker severe. Giff?22442161? Asthma aggravated unmtery Hosp-tamed Ger?224. rer It]? mare Aslrl'na aggravated Untrxerv Hosprtattzed car-224.1 truer Fr42r'c Asthma aggravated unrelated LIre-mreatenrng MF MDI 200 men BID 097-222-3842 Fer Asthma aggravated Unltkely severet Hosprtalzea I Asthma aggravated I Unreratea I Severe MOI ?00 I'lng BID. aggravated IUnretarad Severe MDI eon meg BID ISM-22224804 I Imam-t I Asmma aggravated IUnItIter ISevere.Hosptlalzeo 400m) meg BID tar-2194 I tarsarw I Aslnma Worsening I Unttxely I Severe: muster/0135 I Mlsarw IAs?'ma I Unliker I severe. Dre FISC MDI 250:50 meg BID P04 Ismoroma IAsll?I'na Exacerba?bon I I Severe. I DPI 250/50 meg BID Poarnsr Irrmao new Untrxetv Severe. 10 meg BID 195 Fr51rw IAsll'I'na ISevere. Hospnattzed. 0th BDP MOI 188 BID car-metreoe I Fer Asthma aggravated Poss-me? Ltretnremenrng; Hosprtattzed Placebo 097-2034er39 M: I Asthma aggravated unrrketv Hoaprtattzed er I waarw Severe. on: a' Sex: male; remale Age I5 In years Race: 5 Elam: Camastan; wnne. DIC Reference ID: 3361223 Treatment-related Adverse Events, pooled for the pivotal trials, for the mometasoneonly treatment arms, are shown here. There are no unexpected terms, in line with other ICS programs. The other studies identified by the Sponsor as providing supportive safety have similar reported treatment related AEs. I will look more closely at those studies not reviewed in the Dulera program, to make sure there are no other outliers or concerns. Reference ID: 3361223 19 DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Silver Spring MD 20993 NDA 205641 NDA ACKNOWLEDGMENT Merck Sharp & Dohme Corp. One Merck Drive P.O. Box 100 Whitehouse Station, NJ 08889 Attention: Elinor Chen, PhD Director, Worldwide Regulatory Affairs Dear Dr. Chen: We have received your New Drug Application (NDA) submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for the following: Name of Drug Product: Asmanex HFA Date of Application: June 26, 2013 Date of Receipt: June 27, 2013 Our Reference Number: NDA 205641 Unless we notify you within 60 days of the receipt date that the application is not sufficiently complete to permit a substantive review, we will file the application on August 26, 2013, in accordance with 21 CFR 314.101(a). If you have not already done so, promptly submit the content of labeling [21 CFR 314.50(l)(1)(i)] in structured product labeling (SPL) format as described at http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Failure to submit the content of labeling in SPL format may result in a refusal-to-file action under 21 CFR 314.101(d)(3). The content of labeling must conform to the content and format requirements of revised 21 CFR 201.56-57. You are also responsible for complying with the applicable provisions of sections 402(i) and 402(j) of the Public Health Service Act (PHS Act) [42 USC §§ 282 (i) and (j)], which was amended by Title VIII of the Food and Drug Administration Amendments Act of 2007 (FDAAA) (Public Law No, 110-85, 121 Stat. 904). Reference ID: 3338341 NDA 205641 Page 2 The NDA number provided above should be cited at the top of the first page of all submissions to this application. Send all submissions, electronic or paper, including those sent by overnight mail or courier, to the following address: Food and Drug Administration Center for Drug Evaluation and Research Division of Pulmonary, Allergy, and Rheumatology Products 5901-B Ammendale Road Beltsville, MD 20705-1266 All regulatory documents submitted in paper should be three-hole punched on the left side of the page and bound. The left margin should be at least three-fourths of an inch to assure text is not obscured in the fastened area. Standard paper size (8-1/2 by 11 inches) should be used; however, it may occasionally be necessary to use individual pages larger than standard paper size. Non-standard, large pages should be folded and mounted to allow the page to be opened for review without disassembling the jacket and refolded without damage when the volume is shelved. Shipping unbound documents may result in the loss of portions of the submission or an unnecessary delay in processing which could have an adverse impact on the review of the submission. For additional information, please see http://www.fda.gov/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/Drug MasterFilesDMFs/ucm073080.htm. Secure email between CDER and applicants is useful for informal communications when confidential information may be included in the message (for example, trade secrets or patient information). If you have not already established secure email with the FDA and would like to set it up, send an email request to SecureEmail@fda.hhs.gov. Please note that secure email may not be used for formal regulatory submissions to applications. If you have any questions, call me at (301) 796-3769. Sincerely, {See appended electronic signature page} Jessica K. Lee, PharmD Regulatory Project Manager Division of Pulmonary, Allergy, and Rheumatology Products Office of Drug Evaluation II Center for Drug Evaluation and Research Reference ID: 3338341 --------------------------------------------------------------------------------------------------------This is a representation of an electronic record that was signed electronically and this page is the manifestation of the electronic signature. --------------------------------------------------------------------------------------------------------/s/ ---------------------------------------------------JESSICA K LEE 07/09/2013 Reference ID: 3338341 PIND 112669 Mometasone MDI We refer to the Preliminary Meeting Comments sent to you on September 9, 2011. In an email correspondence you requested clari?cation of comments. Below are responses (in normal font) to your questions (italics). 1. Referring to your response to Question 1 a, it is our understanding that this is requesting an analysis similar to that provided for in-vitro dose proportionality for MF in Section 3.2.P. 2. 4. 7., In- Vitro Dose Proportionality, in the Dulera NDA 22?518. Please clari?/ whether we are interpreting this comment correctly. Yes, we request that you submit an analysis for in-vitro dose proportionality similar to that provided in NDA 22-518 for Dulera. 2. Referring to your response to Question 2, we understand the comment to be highlighting a potential labeling dif?culty rather than one of approvability of the 400 strength. Please con?rm that this interpretation is correct. One possible approach to labeling would be to describe the change ?om baseline data with the to- be?marketed product and then discuss e?icacy data at that dose obtained with a similar with transparency regarding the conditions under which that data was collected. While we appreciate that detailed labeling discussions may be premature at this time, your comments on the acceptability of this general approach would be helpful to us going forward. The response to Question 2 is in reference to labeling, not to approvability. It is premature to discuss speci?c labeling at this time. In general, we note that inclusion of ef?cacy data using the older mometasone furoate formulation will be problematic. Reference ID: 3015057 Reference ID: 3501120 PIND 1 12669 Mometasone MDI Drafted by: Chung/ September 13, 2011 Initialed by: Sandy Barnes/ September 14, 2011 Peri for A Schroeder/ September 14, 2011 Peri/ September 14, 2011 Chaudhry/ September 14, 2011 Susan Limb/ September 14, 2011 Badrul A. Chowdhury/ September 14, 201 1 Finalized by: cchung/ September 14, 2011 Reference ID: 3015057 Reference ID: 3501120 This is a representation of an electronic record that was signed electronically and this page is the manifestation of the electronic signature. CHRISTINE CHUNG 09/14/2011 Reference ID: 3015057 Reference ID: 3501120 ?magma. 49 a o? i DEPARTMENT OF HEALTH AND HUMAN SERVICES 3% Food and Drug Administration Silver Spring MD 20993 FIND 1 12669 MEETING PRELIMINARY COMMENTS Merck Co., Inc. 2000 Galloping Hill Road Kenilworth, NJ 07033 Attention: Elinor Chen, Director, Worldwide Regulatory Affairs Dear Dr. Chen: Please refer to your Pre-Investigational New Drug Application ?le for Mometasone Furoate Metered Dose Inhaler (MDI). We also refer to your July 12, 2011, correspondence, received July 12, 2011, requesting a meeting to discuss the planned NDA for mometasone furoate MDI for maintenance treatment of asthma in patients 12 years of age and older. This material consists of our preliminary responses to your questions and any additional comments in preparation for the discussion at the meeting scheduled for September 13, 2011, at 4:00 P.M., between Merck Co, Inc. and the Division of Pulmonary, Allergy, and Rheumatology Products. We are sharing this material to promote a collaborative and successful discussion at the meeting. The meeting minutes will re?ect agreements, important issues, and any action items discussed during the meeting and may not be identical to these preliminary comments followng substantive discussion at the meeting. However, if these answers and comments are clear to you and you determine that further discussion is not required, you have the option of cancelling the meeting (contact the regulatory project manager If you choose to cancel the meeting, this document will represent the of?cial record of the meeting. If you determine that discussion is needed for only some of the original questions, you have the option of reducing the agenda and/or changing the format of the meeting from face to face to teleconference). It is important to remember that some meetings, particularly milestone meetings, can be valuable even if the premeeting communications are considered suf?cient to answer the questions. Note that if there are any major changes to your development plan, the purpose of the meeting, or the questions based on our preliminary responses, we may not be prepared to discuss or reach agreement on such changes at the meeting although we will try to do so if possible. If any modi?cations to the development plan or additional questions for which you would like CDER feedback arise before the meeting, contact the RPM to discuss the possibility of including these items for discussion at the meeting. Attached are the FDA responses (normal font) to your questions (italics) Reference ID: 3012633 Reference ID: 3501120 PIND 1 12669 Page 2 QUESTIONS AND RESPONSES Chemistry, Manufacturing and Controls Question 1a: Does the Agency agree that the characterization studies conducted for are applicable to the MF and do not need to be repeated? Yes, we agree, with the exception that close proportionality testing should be repeated on the proposed mometasone furoate (MF) MDI. Question 1 b: Does the Agency agree with the proposed stability strategy to support the You have proposed one new batch of MP MDI product per strength to be placed on stability with 12 months of data in the NDA, and one batch per strength of the older clinical/stability batches with 24 months of data in the NDA. Yes, we concur. Additional Comment: Include the following in your future NDA: complete CMC information and data (including stability data) for the older mometasone furoate MDI ?Asmanex used in your clinical studies. In addition, provide comparative summary data for the performance of this Asmanex MDI product with the proposed to-be-marketed mometasone furoate MDI graphical and tabular data). Clinical Question 2: The Sponsor believes that the studies that were completed in the asthma program and in the original MF program adequately characterize the e?icacy and safety of MF monotherapy via an device and that no additional clinical ef?cacy or safety studies will be required. Does the Agency agree? Yes, we agree. However, we anticipate dif?culty in describing ef?cacy information for the 400 dose level in the label since none of the placebo-controlled trials for the MP 400 dose level were performed with the to-be-marketed formulation. In addition, these placebo-controlled trials did not assess EVI at a prespeci?ed timepoint in the dosing interval such as the trough. Clinical Pharmacology Question 3: The Sponsor believes that the proposed studies contained in the Clinical Pharmacology program submitted for the asthma program adequately characterize the pharmacokinetics of MF from the proposed new MF and that no additional clinical pharmacology studies will be required. Does the Agency agree? Yes, we agree. Reference ID: 3012633 Reference ID: 3501120 PIND 1 12669 Page 3 DATA STANDARDS FOR STUDIES CDER stroneg encourages IND sponsors to consider the implementation and use of data standards for the submission of applications for product registration. Such implementation should occur as early as possible in the product development lifecycle, so that data standards are accounted for in the design, conduct, and analysis of studies. CDER has produced a web page that provides speci?cations for sponsors regarding implementation and submission of study data in a standardized format. This web page will be updated regularly to re?ect growing experience in order to meet the needs of its reviewers. The web page may be found at the following link: onicSubrnissions/ucm248635.htm PRESCRIBING INFORMATION Proposed prescribing information (PI) submitted with your application must conform to the content and format regulations found at 21 CFR 201.56 and 201.57. Summary of the Final Rule on the Requirements for Prescribing Information for Drug and Biological Products, labeling guidances, sample tool illustrating Highlights and Table of Contents, an educational module concerning prescription drug labeling, and fictitious prototypes of prescribing information are available at: 084159.11tm. We encourage you to review the information at this website and use it as you draft prescribing information for your application. MANUFACTURING FACILITIES To facilitate our inspectional process, the Division of Manufacturing and Product Quality in Of?ce of Compliance requests that you clearly identify in a Single location, either on the Form FDA 356h, or an attachment to the form, all manufacturing facilities associated with your application. Include the full corporate name of the facility and address where the manufacturing function is performed, with the FBI number, and speci?c manufacturing responsibilities for each facility. Also provide the name and title of an onsite contact person, including their phone number, fax number, and email address. Provide a brief description of the manufacturing operation conducted at each facility, including the type of testing and DMF number (if applicable). Each facility should be ready for GMP inspection at the time of submission. Consider using a table similar to the one below as an attachment to Form FDA 356h. Indicate under Establishment Information on page 1 of Form FDA 356h that the information is provided in the attachment titled, ?Product name, 012345, Establishment Information for Form 356h.? Reference ID: 3012633 Reference ID: 3501120 PIND 112669 Page 4 Federal Drug Master Manufacturing Step(s) . . File or Type of Testing Site Name Site Address R?FiESLBapiron Number [Establishment ?nmber (if function] (CFN) applicable) 1. 2. Corresponding names and titles of onsite contact: . Phone and Site Name Site Address EE?gf$?? Fax Email address - number You should provide, to the Regulatory Project Manager, a hardcopy or electronic version of any materials slides or handouts) to be presented and/or discussed at the meeting. If you have any questions, call me Christine Chung, Regulatory Project Manager, at (301) 796? 3420. Sincerely, {See appended electronic Signature page} Christine Chung, CDR, US. Public Health Service Sr. Regulatory Management Of?cer Division of Pulmonary, Allergy, and Rheumatology Products Of?ce of Drug Evaluation 11 Center for Drug Evaluation and Research Reference ID: 3012633 Reference ID: 3501120 This is a representation of an electronic record that was signed electronically and this page is the manifestation of the electronic signatureCHRISTINE CHUNG 09/09/2011 Reference ID: 3012633 Reference ID: 3501120