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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`NDA 021462/S-051
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`Food and Drug Administration
`Silver Spring MD 20993
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`ACCELERATED APPROVAL
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`Eli Lilly and Company
`Attention: Paul A. Orth, Pharm. D.
`Manager, Global Regulatory Affairs-US
`Lilly Corporate Center
`Drop Code 2543
`Indianapolis, IN 46285
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`Dear Dr. Orth:
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`Please refer to your Supplemental New Drug Application (sNDA) dated August 3, 2017,
`received August 3, 2017, 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,
`in combination with pembrolizumab and carboplatin, for the first-line treatment of metastatic,
`non-squamous, non-small cell lung cancer.
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`APPROVAL & LABELING
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`We have completed our review of this application, as amended. It is approved under the
`provisions of accelerated approval regulations (21 CFR 314.500), effective on the date of this
`letter, for use as recommended in the enclosed agreed-upon labeling. Marketing of this drug
`product and related activities must adhere to the substance and procedures of the referenced
`accelerated approval regulations.
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`WAIVER OF HIGHLIGHTS SECTION
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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
`labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using the FDA
`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 package insert, text for the
`patient package insert), with the addition of any labeling changes in pending “Changes Being
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`Reference ID: 4272929
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`NDA 021462/S-051
`Page 2
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`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 “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 MS Word format, that includes the
`changes approved in this supplemental application, as well as annual reportable changes, and
`annotate each change. To facilitate review of your submission, 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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`ACCELERATED APPROVAL REQUIREMENTS
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`Products approved under the accelerated approval regulations, 21 CFR 314.510, require further
`adequate and well-controlled studies/clinical trials to verify and describe clinical benefit. You
`are required to conduct such studies/clinical trials with due diligence. If postmarketing
`studies/clinical trials fail to verify clinical benefit or are not conducted with due diligence, we
`may, following a hearing in accordance with 21 CFR 314.530, withdraw this approval. We
`remind you of your postmarketing requirement specified in your submission dated June 4, 2018.
`This requirement, along with required completion dates, is listed below.
`
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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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`3424-1
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`Trial Completion:
`Final Report Submission:
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`December 2019
`June 2021
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`Submit clinical protocols to your IND 040061 for this product. In addition, under
`21 CFR 314.81(b)(2)(vii) and 314.81(b)(2)(viii) you should include a status summary of each
`requirement in your annual report to this NDA. The status summary should include expected
`summary completion and final report submission dates, any changes in plans since the last
`annual report, and, for clinical studies/trials, number of patients entered into each study/trial.
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`Reference ID: 4272929
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`NDA 021462/S-051
`Page 3
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`Submit final reports to this NDA as a supplemental application. For administrative purposes, all
`submissions relating to this postmarketing requirement must be clearly designated “Subpart H
`Postmarketing Requirement(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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`PROMOTIONAL MATERIALS
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`Under 21 CFR 314.550, you are required to submit, during the application pre-approval review
`period, all promotional materials, including promotional labeling and advertisements, that you
`intend to use in the first 120 days following marketing approval (i.e., your launch campaign). If
`you have not already met this requirement, you must immediately contact the Office of
`Prescription Drug Promotion (OPDP) at (301) 796-1200. Please ask to speak to a regulatory
`project manager or the appropriate reviewer to discuss this issue.
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`As further required by 21 CFR 314.550, submit all promotional materials that you intend to use
`after the 120 days following marketing approval (i.e., your post-launch materials) at least 30
`days before the intended time of initial dissemination of labeling or initial publication of the
`advertisement. We ask that each submission include a detailed cover letter together with three
`copies each of the promotional materials, annotated references, and approved package insert
`(PI)/Medication Guide/patient PI (as applicable).
`Send each submission directly to:
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`OPDP Regulatory Project Manager
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotions (OPDP)
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
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`Alternatively, you may submit promotional materials for accelerated approval products
`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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`Reference ID: 4272929
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`NDA 021462/S-051
`Page 4
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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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`If you have any questions, call Ingrid Fan, Regulatory Project Manager, at (301) 796-5053.
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`Sincerely,
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`{See appended electronic signature page}
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`Patricia Keegan, M.D.
`Director
`Division of Oncology Products 2
`Office of Hematology and Oncology Products
`Center for Drug Evaluation and Research
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`ENCLOSURE(S):
`Content of Labeling
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`Reference ID: 4272929
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`--------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`--------------------------------------------------------------------------------------------
`/s/
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`PATRICIA KEEGAN
`06/04/2018
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`Reference ID: 4272929
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`(
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