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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`Food and Drug Administration
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`Silver Spring MD 20993
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` NDA 021462/S-053
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`SUPPLEMENT APPROVAL
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` FULFILLMENT OF POSTMARKETING REQUIREMENT
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`Eli Lilly and Company
`Attention: Shannon Kim
`Manager, Global Regulatory Affairs – US
`Eli Lilly and Company
`Indianapolis, IN 46285
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`Dear Ms. Kim:
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`Please refer to your Supplemental New Drug Application (sNDA) dated March 30, 2018,
`received March 30, 2018, and your amendments, submitted under section 505(b) of the Federal
`Food, Drug, and Cosmetic Act (FDCA) for Alimta (pemetrexed disodium) for injection; 500 mg
`and 100 mg.
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`This Prior Approval supplemental new drug application provides for a new indication for Alimta,
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`in combination with pembrolizumab and platinum chemotherapy, for the initial treatment of
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`patients with metastatic, non-squamous, non-small cell lung cancer (NSCLC) with no EGFR or
`ALK genomic tumor aberrations.
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`APPROVAL & LABELING
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`We have completed our review of this supplemental application, as amended. It is approved,
`effective on the date of this letter, for use as recommended in the enclosed, agreed-upon labeling
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` text.
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`WAIVER OF ½ PAGE LENGTH REQUIREMENT FOR HIGHLIGHTS
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`Please note that we have previously granted a waiver of the requirements of 21 CFR
`201.57(d)(8) regarding the length of Highlights of Prescribing Information.
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`CONTENT OF LABELING
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`As soon as possible, but no later than 14 days from the date of this letter, submit the content of
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`labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using the FDA
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`automated drug registration and listing system (eLIST), as described at
`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content
`of labeling must be identical to the enclosed labeling (text for the Prescribing Information,
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`Reference ID: 4383136
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` NDA 021462/S-053
` Page 2
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`Patient Package Insert), with the addition of any labeling changes in pending “Changes Being
`Effected” (CBE) supplements, as well as annual reportable changes not included in the enclosed
`labeling.
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` Information on submitting SPL files using eList may be found in the guidance for industry titled
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`“SPL Standard for Content of Labeling Technical Qs and As” at
`http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.pdf.
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`The SPL will be accessible from publicly available labeling repositories.
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`Also within 14 days, amend all pending supplemental applications that include labeling changes
`for this NDA, including CBE supplements for which FDA has not yet issued an action letter,
`with the content of labeling [21 CFR 314.50(l)(1)(i)] in Microsoft Word format, that includes the
`changes approved in this supplemental application, as well as annual reportable changes. To
`facilitate review of your submission(s), provide a highlighted or marked-up copy that shows all
`changes, as well as a clean Microsoft Word version. The marked-up copy should provide
`appropriate annotations, including supplement number(s) and annual report date(s).
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`REQUIRED PEDIATRIC ASSESSMENTS
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`Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for new
`active ingredients (which includes new salts and new fixed combinations), 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 in pediatric
`patients unless this requirement is waived, deferred, or inapplicable
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`We are waiving the pediatric studies requirement for this application because necessary studies
`are impossible or highly impracticable due to the rarity of pediatric patients with non-squamous
`non-small cell lung cancer (NSCLC).
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`FULFILLMENT OF POSTMARKETING REQUIREMENT(S)/COMMITMENT(S)
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`We have received your submission dated March 30, 2018, containing the final report for the
`following postmarketing requirement listed in the June 4, 2018, approval letter for this
`application.
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`3424-1
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`To submit the results of a multicenter randomized trial or trials to verify and
`describe the clinical benefit of pemetrexed, in combination with platinum therapy
`and pembrolizumab, over pemetrexed-platinum therapy in patients with non-
`squamous non-small cell lung cancer as determined by an improvement in overall
`survival or a large improvement in progression-free survival that is clinically
`meaningful.
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`Trial Completion:
`Final Report Submission:
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`December 2019
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`June 2021
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`Reference ID: 4383136
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` NDA 021462/S-053
` Page 3
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` We have reviewed your submission and conclude that the above requirement was fulfilled.
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`PROMOTIONAL MATERIALS
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`You may request advisory comments on proposed introductory advertising and promotional
`labeling. To do so, submit the following, in triplicate, (1) a cover letter requesting advisory
`comments, (2) the proposed materials in draft or mock-up form with annotated references, and
`(3) the Prescribing Information to:
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`OPDP Regulatory Project Manager
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion (OPDP)
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
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`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 ).
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`You must submit final promotional materials and Prescribing Information, accompanied by a
`Form FDA 2253, at the time of initial dissemination or publication [21 CFR 314.81(b)(3)(i)].
`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
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`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.
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`REPORTING REQUIREMENTS
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`We remind you that you must comply with reporting requirements for an approved NDA
`(21 CFR 314.80 and 314.81).
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`Reference ID: 4383136
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`Sincerely,
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` {See appended electronic signature page}
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`Patricia Keegan, M.D.
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` Director
`Division of Oncology Products 2
`Office of Hematology and Oncology Products
`Center for Drug Evaluation and Research
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` NDA 021462/S-053
` Page 4
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`If you have any questions, call Ingrid Fan, Regulatory Project Manager, at (301) 796-5053.
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`ENCLOSURE(S):
`Content of Labeling
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`Prescribing Information
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`Patient Package Insert
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`Reference ID: 4383136
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`Signature Page 1 of 1
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`This is a representation of an electronic record that was signed
`electronically. Following this are manifestations of any and all
`electronic signatures for this electronic record.
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`/s/
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`PATRICIA KEEGAN
`01/30/2019 03:39:02 PM
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`Reference ID: 4383136
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`(
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