CENTER FOR DRUG EVALUATION AND RESEARCH
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`Approval Package for:
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`2057180rig1s000
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`HELSINN EXHIBIT 2005
`Azurity Pharmaceuticals, Inc. v. Helsinn Healthcare S.A.
`Page 1 of 10 IPR2025-00948
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`CENTER FOR DRUG EVALUATION AND
`RESEARCH
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`2057180rig1s000
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`CONTENTS
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`Reviews / Information Included in this NDA Review.
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`Approval Letter
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`Other Action Letters
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`Labeling
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`REMS
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`Summary Review
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`Officer/Employee List
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`Office Director Memo
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`Cross Discipline Team Leader Review
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`Medical Review(s)
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`Chemistry Review(s)
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`Environmental Assessment
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`Pharmacology Review(s)
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`Statistical Review(s)
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`Microbiology / Virology Review(s)
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`Clinical Pharmacology/Biopharmaceutics Review(s)
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`Other Reviews
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`Risk Assessment and Risk Mitigation Review(s)
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`Proprietary Name Review(s)
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`lieitaitaiialisitaitaliiialicilallicii il IR L e
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`Administrative/Correspondence Document(s)
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`Page 2 of 10
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`CENTER FOR DRUG EVALUATION AND
`RESEARCH
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`2057180rig1s000
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`APPROVAL LETTER
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`Page 3 of 10
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`{ _/ DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`Food and Drug Administration
`Silver Spring MD 20993
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`NDA 205718
`NDA APPROVAL
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`Helsinn Healthcare SA
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`c/o August Consulting, Inc.
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`Attention: Craig Lehmann, PharmD.
`Authorized Representative
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`515 S. Capital of Texas Hwy., Suite #150
`Austin, TX 78746
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`Dear Dr. Lehmann:
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`Please refer to your New Drug Application (NDA) dated and received September 27, 2013,
`submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for
`Akynzeo (netupitant and palonosetron) capsules.
`
`We acknowledge receipt of your amendments dated October 9, 2013: October 31, 2013;
`November 8, 2013; November 14, 2013; November 21, 2013; December 16, 2013; December 20,
`2013; January 9, 2014; January 17, 2014, January 23, 2014; February 4, 2014; February 5, 2014;
`February 14, 2014; February 20, 2014; March 24, 2014; March 26, 2014, March 27, 2014;
`March 28 2014; March 31, 2014; April 4, 2014; April 22, 2014; April 25, 2014; April 30, 2014;
`May 5, 2014; May 12, 2014; May 14, 2014; May 16, 2014; May 21; 2014; May 22, 2014; May
`27,2014; June 5, 2014; June 17, 2014; June 18, 2014; June 30, 2014; July 3, 2014; July 7, 2014;
`July 15, 2014; July 16, 2014; July 29, 2014; August 5, 2014; August 8, 2014; August 18, 2014;
`August 21, 2014; August 28, 2014; September 10, 2014; September 15, 2014; September 16,
`2014; September 17, 2014; September 23, 2014; September 25, 2014; and September 26, 2014.
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`This new drug application provides for the use of Akynzeo (netupitant and palonosetron), a fixed
`combination for prevention of acute and delayed nausea and vomiting associated with initial and
`repeat courses of cancer chemotherapy, including, but not limited to, highly emetogenic
`chemotherapy.
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`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.
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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(1)] in structured product labeling (SPL) format using the FDA
`automated drug registration and listing system (eLIST), as described at
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`NDA 205718
`Page 2
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`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). Information on submitting SPL files using eLIST may be found in the
`guidance for industry SPL Standard for Content of Labeling Technical Qs and As, available at
`http://www.fda.gov/downloads/Drugs/GuidanceComplianceR egulatoryInformation/Guidances/U
`CMO072392.pdf.
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`The SPL will be accessible via publicly available labeling repositories.
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`CARTON AND IMMEDIATE CONTAINER LABELS
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`Submit final 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 eCTD Specifications (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 purposes, designate this submission
`“Final Printed Carton and Container Labels for approved NDA 205718.” Approval of this
`submission by FDA is not required before the labeling is used.
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`ADVISORY COMMITTEE
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`Your application for Akynzeo was not referred to an FDA advisory committee because it is not
`the first in its class and the application did not raise significant public health questions on the
`role of Akynzeo in the diagnosis, cure, mitigation, treatment, or prevention of a disease. Outside
`expertise was not necessary; and there were no controversial issues that would benefit from
`advisory committee discussion.
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`REQUIRED PEDIATRIC ASSESSMENTS
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`Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355¢), 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.
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`We are deferring submission of your pediatric studies until April 30, 2022, because this product
`1s ready for approval for use in adults and the pediatric studies have not been completed.
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`Your deferred pediatric studies required under section 505B(a) of the FDCA are required
`postmarketing studies. The status of these postmarketing studies must be reported annually
`according to 21 CFR 314.81 and section 505B(a)(3)(B) of the FDCA. These required studies are
`listed below.
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`NDA 205718
`Page 3
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`2769-1 An 8-week GLP toxicology study with fertility evaluation in neonatal rats treated
`with netupitant alone.
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`Final Protocol Submission: 05/30/2015
`Study Completion: 12/30/2015
`Final Report Submission: 03/30/2016
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`2769-2 A PK/PD dose finding study of netupitant to characterize the netupitant PK/PD
`relationship for complete response in the delayed phase following oral
`administration of a single dose of netupitant given concomitantly (in separate
`formulations) with an oral single administration of palonosetron in pediatric
`cancer patients ages 0 tol7 years undergoing treatment with emetogenic
`chemotherapy, including highly emetogenic chemotherapy. You must conduct
`this study with an age appropriate formulation.
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`Final Protocol Submission: 11/01/2015
`Study Completion: 04/30/2018
`Final Report Submission: ~ 09/30/2018
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`2769-3 An adequate, well-controlled, double-blind, randomized study to evaluate the
`safety and efficacy of a dose of the netupitant/palonosetron fixed
`combination compared to standard therapy in pediatric cancer patients ages 0 to
`17 years undergoing treatment with emetogenic chemotherapy, including highly
`emetogenic chemotherapy. You must conduct this study with an age appropriate
`formulation.
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`Final Protocol Submission: 04/30/2019
`Study Completion: 12/31/2021
`Final Report Submission: 04/30/2022
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`Submit the protocols to your IND 073493, with a cross-reference letter to this NDA.
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`Reports of these required pediatric postmarketing studies must be submitted as a new drug
`application (NDA) or as a supplement to your approved NDA with the proposed labeling
`changes you believe are warranted based on the data derived from these studies. When
`submitting the reports, please clearly mark your submission "SUBMISSION OF REQUIRED
`PEDIATRIC ASSESSMENTS" in large font, bolded type at the beginning of the cover letter of
`the submission.
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`POSTMARKETING COMMITMENTS SUBJECT TO REPORTING REQUIREMENTS
`UNDER SECTION 506B
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`We remind you of your postmarketing commitments:
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`NDA 205718
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`2769-4 In vivo drug interaction study to evaluate the duration of inhibitory effects of
`Akynzeo (netupitant and palonosetron) on CYP3A4 enzyme activity beyond 4
`days after Akynzeo (netupitant and palonosetron) administration.
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`The timetable you submitted on July 29, 2014, states that you will conduct this study according
`to the following schedule:
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`Final Protocol Submission: 01/2015
`Study Completion: 01/2016
`Final Report Submission: 06/2016
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`2769-5 Invitro study to evaluate the potential of netupitant to act as a substrate for P-gp
`transporter 1n a bi-directional transport assay system.
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`The timetable you submitted on July 29, 2014, states that you will conduct this study according
`to the following schedule:
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`Final Report Submission: 10/2014
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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, in triplicate, a cover letter requesting advisory comments, the
`proposed materials in draft or mock-up form with annotated references, and the package insert
`to:
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`Food and Drug Administration
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`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion
`5901-B Ammendale Road
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`Beltsville, MD 20705-1266
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`As required under 21 CFR 314.81(b)(3)(1), 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/ReportsManualsF orms/Forms/UCMO083570.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.
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`NDA 205718
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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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`MEDWATCH-TO-MANUFACTURER PROGRAM
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`The MedWatch-to-Manufacturer Program provides manufacturers with copies of serious adverse
`event reports that are received directly by the FDA. New molecular entities and important new
`biologics qualify for inclusion for three years after approval. Your firm is eligible to receive
`copies of reports for this product. To participate in the program, please see the enrollment
`instructions and program description details at
`http://www.fda.gov/Safety/MedWatch/HowToReport/ucm166910.htm.
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`POST APPROVAL FEEDBACK MEETING
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`New molecular entities and new biologics qualify for a post approval feedback meeting. Such
`meetings are used to discuss the quality of the application and to evaluate the communication
`process during drug development and marketing application review. The purpose is to learn
`from successful aspects of the review process and to identify areas that could benefit from
`improvement. If you would like to have such a meeting with us, call the Regulatory Project
`Manager for this application.
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`PDUFA V APPLICANT INTERVIEW
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`FDA has contracted with Eastern Research Group, Inc. (ERG) to conduct an independent interim
`and final assessment of the Program for Enhanced Review Transparency and Communication for
`NME NDAs and Original BLAs under PDUFA V (‘the Program’). The PDUFA V Commitment
`Letter states that these assessments will include interviews with applicants following FDA action
`on applications reviewed in the Program. For this purpose, first-cycle actions include approvals,
`complete responses, and withdrawals after filing. The purpose of the interview is to better
`understand applicant experiences with the Program and its ability to improve transparency and
`communication during FDA review.
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`ERG will contact you to schedule a PDUFA V applicant interview and provide specifics about
`the interview process. Your responses during the interview will be confidential with respect to
`the FDA review team. ERG has signed a non-disclosure agreement and will not disclose any
`identifying information to anyone outside their project team. They will report only anonymized
`results and findings in the interim and final assessments. Members of the FDA review team will
`be interviewed by ERG separately. While your participation in the interview is voluntary, your
`feedback will be helpful to these assessments.
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`NDA 205718
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`If you have any questions, call Mary Chung, Regulatory Project Manager, at (301) 796-0260.
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`Sincerely,
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`{See appended electronic signature page}
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`Julie Beitz, M.D.
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`Director
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`Office of Drug Evaluation III
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`Center of Drug Evaluation and Research
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`Enclosure(s):
`Content of Labeling
`Carton and Container Labeling
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`e age Gol 10 -
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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.
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`/s/
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`JULIE G BEITZ
`10/10/2014
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