DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Silver Spring MD 20993 NDA 207793 NDA APPROVAL Merrimack Pharmaceuticals, Inc. Attention: Michael Slater Vice President, Regulatory Affairs One Kendall Square, Suite B7201 Cambridge, MA 02139 Dear Mr. Slater: Please refer to your New Drug Application (NDA) dated April 24, 2015, received April 24, 2015, submitted pursuant to section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act (FDCA) for Onivyde (irinotecan liposome injection), 43 mg/10 mL single dose vial. We acknowledge receipt of your amendments dated April 29, May 4, May 14, May 29, June 4, June 30, July 14, July 16, July 21, July 23, July 30, July 31, August 3, August 11, August 24, August 25, September 15, September 22, September 24, September 25, October 8, October 9, October 16, October 19, October 20 and October 21, 2015. This new drug application provides for the use of Onivyde (irinotecan liposome injection), in combination with 5-fluorouracil and leucovorin, for the treatment of patients with metastatic adenocarcinoma of the pancreas that has progressed following gemcitabine-based therapy. This approval includes the following limitation of use: Onivyde is not indicated as a single agent for the treatment of patients with metastatic adenocarcinoma of the pancreas. APPROVAL & LABELING We have completed our review of this application, as amended. It is approved, effective on the date of this letter, for use as recommended in the enclosed agreed-upon labeling text. Reference ID: 3836766 NDA 207793 Page 2 CONTENT OF LABELING As soon as possible, but no later than 14 days from the date of this letter, submit the content of labeling [21 FR 3 1450(1)] in structured product labeling (SPL) format using the FDA automated ding registration and listing system as described at gov/F orIndustiy/DataStandards/ Stiuc tin?edProduc tLabelin g1 Content of labeling must be identical to the enclosed labeling text for the package insert. Information on submitting SPL ?les using may be found in the guidance for industiy SPL Standard for Content of Labeling Technical Qs and As, available at . M072392.pdf. The SPL will be accessible Via publicly available labeling repositories. CARTON AND HVIMEDIATE CONTAINER LABELS Submit ?nal printed carton and immediate container labels that are identical to the enclosed carton and immediate container labels as soon as they are available, but no more than 30 days after they are printed. Please submit these labels electronically according to the guidance for industry Providing Regulatory Submissions in Electronic Format Human Pharmaceutical Product Applications and Related Submissions Using the Speci?cations (June 2008). Alternatively, you may submit 12 paper copies, with 6 of the copies individually mounted on heavy-weight paper or similar material. For administrative pinposes, designate this submission ?Final Printed Carton and Container Labels for approved NDA 207793.? Approval of this submission by FDA is not required before the labeling is used. Marketing the product(s) with FPL that is not identical to the approved labeling text may render the product misbranded and an unapproved new ding. CHEMISTRY MANUFACTURING AND CONTROLS A 21 month expiration dating period is granted for the 43 mg/ 10 mL single use vial when stored at refrigerated storage conditions with protection from light and freezing. (m4) Reference ID: 3836766 NDA 207793 Page 3 REQUIRED PEDIATRIC ASSESSMENTS 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. Because this drug product for this indication has an orphan drug designation, you are exempt from this requirement. PROMOTIONAL MATERIALS You may request advisory comments on proposed introductory advertising and promotional labeling. To do so, submit, in triplicate, a cover letter requesting advisory comments, the proposed materials in draft or mock-up form with annotated references, and the package insert, Medication Guide, and patient PI (as applicable) to: OPDP Regulatory Project Manager Food and Drug Administration Center for Drug Evaluation and Research Office of Prescription Drug Promotion 5901-B Ammendale Road Beltsville, MD 20705-1266 Alternatively, you may submit a request for advisory comments electronically in eCTD format. For more information about submitting promotional materials in eCTD format, see the draft Guidance for Industry (available at: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U CM443702.pdf ). As required under 21 CFR 314.81(b)(3)(i), you must submit final promotional materials, and the package insert, at the time of initial dissemination or publication, accompanied by a Form FDA 2253. Form FDA 2253 is available at http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf. Information and Instructions for completing the form can be found at http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf. For more information about submission of promotional materials to the Office of Prescription Drug Promotion (OPDP), see http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm. METHODS VALIDATION We have not completed validation of the regulatory methods. However, we expect your continued cooperation to resolve any problems that may be identified. Reference ID: 3836766 NDA 207793 Page 4 REPORTING REQUIREMENTS We remind you that you must comply with reporting requirements for an approved NDA (21 CFR 314.80 and 314.81). If you have any questions, please call Deanne Varney, Lead Regulatory Project Manager, at (301) 796-0297. Sincerely, {See appended electronic signature page} Patricia Keegan, M.D. Director Division of Oncology Products 2 Office of Hematology and Oncology Products Center for Drug Evaluation and Research Enclosures: Content of Labeling Carton and Container Labeling Reference ID: 3836766 --------------------------------------------------------------------------------------------------------This is a representation of an electronic record that was signed electronically and this page is the manifestation of the electronic signature. --------------------------------------------------------------------------------------------------------/s/ ---------------------------------------------------PATRICIA KEEGAN 10/22/2015 Reference ID: 3836766