Doc 2-10 Filed 10112117 Pg-2 of 9 Pg ID 1525 or HEALTH HUMAN SERVICES Rockville M02057 MAR 3 0 am TRANSMITTED VIA FACSIMILE Cy'nthia Chianese Assistant Director Regulatory Affairs Janssen Phannacuetica 1125 Trenton-Harbourton Road P.0. Box 200 Titusville, NJ 08560-0200 RE: NBA 19-813 . Duragesic (fentanyl transdermal system) MACMIS ID #8664 Dear Ms. Chianese: Reference is made to Janssen Pharmaceutiea?s (Janssen) letter, dated February 29, 2000, in re5ponse to a. letter from the Division of Drug Marketing, Advertising, and Communications (DDMAC), dated February 15, 2000. Our letter. concerned the, alleged dissemination of ?homemade? promotional pieces that promoted Duragesic (fentanyl transdennal system) . capsules in violation of the Federal Food, Drug, and Cosmetic Act (Act) and its implementing . - regulations. We requested that you investigate the extent that these ?homemade? pieces were used to promote Duragesic, the number 'of health care professionals who received these pieces, and that you provide the complete promotional pieces as they were allegedly disseminated. In your letter, you described the circumstances in which the violative promotional materials were disseminated. Additionally, your letter commented on your policy for prohibiting dissemination of homemade materials by your sales force, and speci?ed the corrective actions taken to ensure that this activity will not continue. We have reviewed the ?homemade? promotional pieces and have determined that they are false or misleading because they contain misrepresentations of safety information, broaden Duragesic?s indication-contain unsubstantiated claims, and lack fair balance. Speci?c examples include, but are not limited to, the following ?homemade? promotional pieces: - DOC 2-10 Filed 10/12/1526 Chianese . page 2 anssen Pharmaceutica NBA #1 9-81 3 December-9, 1999 Mailing - ?The #1 Reason to convert your patients to the Duragcsic Patch? . . Misrepresentation of Safety Information Promotional materials are false or misleading if they contain representations or suggestions that a drug?s safety or effectiveness is comparable or superior to another drug when such has not been demonstrated by substantial evidence. Examples of your claims that misrepresent the safety pro?le for Duragesic include: 0 You preSent the claim, ?Signi?cantly LESS constipation!" This claim suggests that Duragesic is associated with signi?cantly less constipation than other avail-able Opioids. However, this claim has not been demonstrated by substantial evidence. Therefore, without supporting substantial evidence, this claim ts false or misleading Fm'thermore, this claim misrepresents the safety pro?le for Duragesic because it minimizes the risk of constipation that 15 associated with Duragesic therapy Please refer to our untitled letter to Janssen, dated March 5, 1998, addressing this issue. I You present the claim, ?Low abuse potential!? This claim suggests that Duragesic has less potential for abuse than other currently available opioids. However, this claim has not been demonstrated by substantial evidence. Furthermore, thiscl-aim is contradictory to information in the approved product labeling (PI) that states, ?Fenianyl is a Schedule II controlled substance and can produce drug dependence similar to that produced by morphine.? Therefore, this claim 15 false or misleading. Broadening of indication Promotional materials are misleading if they contain a representation or suggestion that a drug is more useful a broader range of conditions or patients than has been demonstrated by substantial evidence. I- You present the claim, ?It's not just for end stage cancer anymore!? This claim suggests that Duragesic can be used for any type of pain management. However, the PI for Duragesic states, ?Dmgesic (fentanyl transdermal system) is indicated in the management of chronic pain in patients who require continuous opiod analgesia for pain that cannot be managed by lesser means. Therefore, the suggestion that Duragesic can be used for any type of pain management promotes Duragesic? for a much broader use than 15 recommended 1n the PI, and thus, 15 misleading. In addition, the suggestion that Duragesic can be used to treat any kind of pain is contradictory to the boxed warning in the Pl. speci?cally the PI sates, BECAUSE SERIOUS OR LIFE-THREATENING COULD OCCUR, (FENTANYL TRANSDERMAL svsrem IS CONTRAINDICATED. Doc 2-10 Filed 10/12/1528 Chianese . page 3 Janssen Pharmaceutica NDA #1 9-8 1 3 - In the management of acute or post-operative pain, including use in out-patient surgeries. Unsubstantiated Claims You present several unsubstantiated claims for Duragesic throughout this ?homemade? promotional piece. Examples of your unaubstantiated claims include: 0 You present the claim, f?Preferred regimen: 2 it per week versus 2 it per day!? This claim suggests that patients prefer Duragesic to other available oral opioids that are taken twice daily. However, this patient preference claim is not supported by substantial evidence. Therefore, we consider this claim false or misleading. '0 You present the claim, ?Easy for Patient Compliance.? This claim suggests that Duragesic may enhance patient compliance when compared to other opioids. However, this claim is not supported by speci?c compliance data, and therefore, is false or misleading. . You present quality of life claims, including but not limited to, ?And the reason to convert - yourpatients to the Diuagesic patch: QUALITY OF and . .without pain, patient?s sleep better, increase daily activities, and spend more quality time with their families.? Health related quality of life claims such as these require substantial supporting evidence' in the. form of adequate and well-controlled studies designed to speci?cally assess these outcomes. Therefore, without substantiation from adequate studies, the claims presented in this ?homemade? promotional piece are misleading, Lam Promotional materials must present information relating to the contraindications, warnings, precautions, and side effects with a prominence and readability reasonably comparable to the - presentation of information relating to the effectiveness of the product. This ?homemade" promotional piece is lacking 1n fair balance with respect to the content and presentation of risk information related to the use of Duragesic. 0 Although this piece contains numerous claims for the ef?cacy and safety of Duragesic, you have not presented any risk information concerning the boxed warnings, . contraindications, warnings, precautions, or side e??ects associated with Duragesic?s use (emphasis added). Therefore, this promotional piece is lacking in fair balance, or otherwise misleading, because it fails to address important risks and restrictions associated with Duragesic therapy. DOC 2~10 Filed Pg 6 of 9 Pg ID 1529 Chinese I . page 4 Janssen Pharmaceutica NDA #19-813 Cost ?3r Therapy (30 Days) Misrepresentation of Safety Information 0 Your present the claim, ?Duragesic results in much less Constipation compared to Oxycontin (Senokot $1 -00/day). However, this comparative claim to Oxycontin is not supported by substantial evidence. Therefore, this unsubstantiated superiority claim' IS false or misleading. Furthermore, this claim minimizes the risk of constipation that is associated with Duragesic therapy Cost Comparison 0 You present a table that compares the price of di?emnt of Duragesic and Oxycontin from eight retail pharmacies. This table is followed by the claim that esic is marginally less expensive.? However, this comparison is misleading because it implies that Duragesic is equally safe, e?ective, and interchangeable with Oxycontin for the doses compared. Furthermore, this cost information lacks substantiation and does not provide a reference as to the source of the cost information presented. in Prometional materials must be submitted to the FDA under Form FDA 2253 at the time of initial dissemination. However, om records indicate these promotional materials were not submitted at the time of initiai use. We have reviewed your response and actions taken in response to the dissemination of this violative promotional piece. We do not wish to comment on your internal processes, however we do acknowledge your investigation and the corrective actions taken to prevent reoccurrence of this type of violative promotional activity. At this time we have no further. questions and consider the matter regarding the ?homemade? promotional pieces described in this letter to be - closed. However, you should immediately cease distribution. of all other promotional materials for Duragesic that contain the same or similar claims or presentations. You should submit a written response to us on or before April 13, 2000, describing your intent and plans to comply with the above Your letter should include a list of materials discontinued and the date on which these materials were discontinued. If you have any further questions. or comments, please contact me by facsimile at (301) 594- 6771, or by writing at the Food and Drug Administration, Division of Drug Marketing, - Advertising and Communications, RFD-42, Rm. 173-20, 5600- Fishers Lane, Rockville, MD 20857. We remind you that only written considered of?cial. Doc 2-10 Filed 10/12/1531 URACESIC I ?My! Transdermal System Reasons to Switch Your Patients to the Duragesic Patch: #10 It's not just for end stage cancer anymore! #9 .. DURAGESIC - the LONGEST acting opioid! #8 Signi?cantly LBS constipation! #7 EASY to Titrate - Remember the 6-30?60 rule! #6 Cost Effective #5 No clock watching as with oral opioids! #4 Preferred regimen: 2 per week versus 2 1: per day! . #3 Low abuse potential! #2 I EASY for Patient Compliance .. And the #1 reason to convert your patients to the Duragesic patch: its or LIFE _Durageslc gives patients the FREEDOM to enjoy their lives without focus on their pain. And without-pain. patients sleep better. Increase daily activities. and spend more quality time with their families. They may even find time to stop and smell the ?owersList is complete, and now you know just how much your patients with chronic non-malignant pain can bene?t from Durageslc. With these seeds. enjoy the blooms of your newly planted habit of writing Duragesic. The New Standard in the New Millennium For Chronic Non-Malignant Pain ?manhrr. a em DOC 2-10 Filed 10/12/1530 Chinese . page 5 Janssen Pharmaceutiea NDA #19-813 In all future 'cori'espondence regarding this matter, please refer to the MACMIS 8664 and the NDA number. Sincerely, . Spencer Saiis, Pharm.D-. Regulatory Review Of?cer Division of Drug Marketing, Advertising and Communications DOC 210 Filed 10/12/1532 Target . Put?ix Walmarl Perkins Medicine Shappe Eckerds Walgreens Pill Box Avg Cost . 119.38 127.78 133.92 139.14 125.78 162.58 135.98 - 128.00 134 Cost of Therapy (39 Days) 25mcg 20mg 155.39 139.39 141.88 156.88 136.89 149.59 132.95 137.40. 144 50mcg 40mg 181.38 256.69 183.78 246.99 - 213.24 247.63 209.86 266.24 191.78 ?238.89 217.38 254.69 209.98 -235.97 198.00 237.00 -201 "248' 281.98 287.98 331 .08 326.8 299.78 347.98 323.98 308.00 313 402.99 450.99 461 .21 486.82 590.89 485.19 .447-95 450.00 .472 Duragesic results In much less Constipation compared to Oxyeann (881101101 :1 .00198y) Duragesic is marginally less expensive. Dungeslc Oxycontin Dungeon: Oxycontin Dungulc Oxycontin Duncan _75mcg 80mg 100ch 347.98 357.98 407.68 "8 403.28 371 .78 399.78 405.98 360.00 382 Attachment II