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`U.S. FOOD & DRUG
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`ADMINISTRATION
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` BLA 125514/S-136
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` ACCELERATED APPROVAL
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`Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
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`Attention: Michelle Ponpipom, RPh, MPH
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`Senior Director, Global Regulatory Affairs
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`126 E. Lincoln Avenue, P.O. Box 2000
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`RY34B-332
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`Rahway, NJ 07065
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`Dear Ms. Ponpipom:
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`Please refer to your supplemental biologics license application (sBLA), dated and
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`received October 21, 2022, and your amendments, submitted under section 351(a) of
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`the Public Health Service Act for Keytruda (pembrolizumab).
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` This Prior Approval supplemental biologics license application provides for the following
` new indication for Keytruda: Keytruda, in combination with enfortumab vedotin, is
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` indicated for the treatment of adult patients with locally advanced or metastatic
` urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy.
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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
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`provisions of accelerated approval pursuant to section 506(c) of the Federal Food,
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`Drug, and Cosmetic Act (FDCA) and 21 CFR 601.41, effective on the date of this letter,
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`for use as recommended in the enclosed agreed-upon labeling.
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`Marketing of this drug product and related activities must adhere to the substance and
`procedures of the accelerated approval statutory provisions and regulations.
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`WAIVER OF HIGHLIGHTS 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
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`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, via
`the FDA automated drug registration and listing system (eLIST), the content of labeling
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`[21 CFR 601.14(b)] in structured product labeling (SPL) format, as described at
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`Reference ID: 5152154
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`Page 1 of 5
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`MERCK EX1160
`Merck Sharp & Dohme LLC v. The Johns Hopkins University
`IPR2024-00240
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` BLA 125514/S-136
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` Page 2
` FDA.gov,1 that is identical to the enclosed labeling (text for the Prescribing Information,
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` and Medication Guide) and include the labeling changes proposed in any pending
` “Changes Being Effected” (CBE) supplements.
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`Information on submitting SPL files using eLIST may be found in the guidance for
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` industry SPL Standard for Content of Labeling Technical Qs and As.2
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`The SPL will be accessible via publicly available labeling repositories.
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`Also, within 14 days, amend all pending supplemental applications that include labeling
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`changes for this BLA, including pending “Changes Being Effected” (CBE) supplements,
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`for which FDA has not yet issued an action letter, with the content of labeling
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`[21 CFR 601.12(f)] in Microsoft Word format that includes the changes approved in this
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`supplemental application, as well as annual reportable changes. To facilitate review of
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`your submission(s), provide a highlighted or marked-up copy that shows all changes, as
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`well as a clean Microsoft Word version. The marked-up copy should provide appropriate
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`annotations, including supplement number(s) and annual report date(s).
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`ACCELERATED APPROVAL REQUIREMENTS
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`Products approved under accelerated approval pursuant to section 506(c) of the FDCA
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`and 21 CFR 601.41 may require further adequate and well-controlled clinical trials
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`intended to verify and describe clinical benefit. You are required to conduct such clinical
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`trials with due diligence. If required postmarketing clinical trials fail to verify clinical
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`benefit or are not conducted with due diligence, we may withdraw this approval. We
`remind you of your postmarketing requirement specified in your submission dated
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`March 7, 2023. This requirement, along with required completion dates, is listed below.
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`This postmarketing clinical trial is subject to the reporting requirements of
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`21 CFR 601.70:
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`4429-1 Conduct clinical trial EV-302, “Enfortumab Vedotin and Pembrolizumab vs.
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`Chemotherapy Alone in Untreated Locally Advanced or Metastatic
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`Urothelial Cancer” and submit the final OS, PFS, ORR and DoR results,
`intended to verify and describe the clinical benefit of enfortumab vedotin in
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`combination with pembrolizumab in patients with untreated locally
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`advanced or metastatic urothelial cancer.
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`03/2025
`Trial Completion:
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`Final Report Submission:
`09/2025
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`1 http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm
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`2 We update guidances periodically. For the most recent version of a guidance, check the FDA Guidance
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`Documents Database at https://www.fda.gov/RegulatoryInformation/Guidances/default.htm.
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`U.S. Food and Drug Administration
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`Silver Spring, MD 20993
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`www.fda.gov
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`Reference ID: 5152154
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`Page 2 of 5
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` BLA 125514/S-136
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` Page 3
`Submit clinical protocols to your IND 122753 for this product. In addition, you must
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`submit status reports of the progress of each requirement not later than 180 days after
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`the date of approval of this drug and every 180 days thereafter (section 506(B)(a) of the
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`FDCA as amended by section 3210(b) of the Food and Drug Omnibus Reform Act of
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`2022). The status summary should include expected trial completion and final report
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`submission dates, any changes in plans since the last report, and, for clinical trials, the
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`number of patients entered in each trial (21 CFR 601.70).
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`Submit final reports to this BLA as a supplemental application. For administrative
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`purposes, all submissions relating to this postmarketing requirement must be clearly
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`designated “Subpart E 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
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`new active ingredients (which includes new salts and new fixed combinations), new
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`indications, new dosage forms, new dosing regimens, or new routes of administration
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`are required to contain an assessment of the safety and effectiveness of the product for
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`the claimed indicationin pediatric patients unless this requirement is waived, deferred, or
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`inapplicable.
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`We are waiving the pediatric study requirement for this application because necessary
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`studies are impossible or highly impracticable.
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`PROMOTIONAL MATERIALS
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`Under 21 CFR 601.45, you are required to submit, during the application pre-approval
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`review period, all promotional materials, including promotional labeling and
`advertisements, that you intend to use in the first 120 days following marketing approval
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`(i.e., your launch campaign). If you have not already met this requirement, you must
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`immediately contact the Office of Prescription Drug Promotion (OPDP) at
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`(301) 796-1200. Please ask to speak to a regulatory project manager or the appropriate
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`reviewer to discuss this issue.
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`As further required by 21 CFR 601.45, submit all promotional materials that you intend
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`to use after the 120 days following marketing approval (i.e., your post-launch materials)
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`at least 30 days before the intended time of initial dissemination of labeling or initial
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`publication of the advertisement. We ask that each submission include a detailed cover
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`letter together with three copies each of the promotional materials, annotated
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`references, and approved Prescribing Information, Medication Guide, and Patient
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`Package Insert (as applicable).
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`For information about submitting promotional materials, see the final guidance for
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`industry Providing Regulatory Submissions in Electronic and Non-Electronic Format-
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`Promotional Labeling and Advertising Materials for Human Prescription Drugs.3
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`3 https://www.fda.gov/media/128163/download
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`U.S. Food and Drug Administration
`Silver Spring, MD 20993
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`www.fda.gov
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`Reference ID: 5152154
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`Page 3 of 5
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` BLA 125514/S-136
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` Page 4
`REPORTING REQUIREMENTS
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`We remind you that you must comply with reporting requirements for an approved BLA
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`(in 21 CFR 600.80 and in 21 CFR 600.81).
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`If you have any questions, call Sherry Hou, PharmD, Regulatory Project Manager,
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`at 240-402-1813.
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`Sincerely,
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`{See appended electronic signature page}
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`Daniel Suzman, MD
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`Deputy Division Director
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`Division of Oncology 1
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`Office of Oncologic Diseases
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`Center for Drug Evaluation and Research
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`ENCLOSURES:
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`• Content of Labeling
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`o Prescribing Information
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`o Medication Guide
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` U.S. Food and Drug Administration
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`Silver Spring, MD 20993
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`www.fda.gov
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`Reference ID: 5152154
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`Page 4 of 5
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`Signature Page 1 of 1
`--------------------------------------------------------------------------------------------
`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.
`--------------------------------------------------------------------------------------------
`/s/
`------------------------------------------------------------
`
`DANIEL L SUZMAN
`04/03/2023 10:53:51 AM
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`Reference ID: 5152154
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`(
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`Page 5 of 5
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