CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`APPLICATION NUMBER:
`22-023
`
`APPROVAL LETTER
`
`HELSINN EXHIBIT 2004
`Azurity Pharmaceuticals, Inc. v. Helsinn Healthcare S.A.
`Page 1 of 6 IPR2025-00947
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`DEPARTMENT OF HEALTH & HUMAN SERVICES Public Health Service
`
`Uiz Food and Drug Administration
`Rockville, MD 20857
`
`NDA 22-023 NDA APPROVAL
`
`Merck & Co., Inc.
`Attention: Nicholas Andrew
`Associate Director, Worldwide Regulatory Affairs
`P.O. Box 2000, RY 33-200
`Rahway, NJ 07065-0900
`
`Dear Mr. Andrew:
`
`Please refer to your new drug application (NDA) dated March 31, 2006, received April 3, 2006,
`submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act for Emend
`(fosaprepitant dimeglumine) for Injection, 115 mg.
`
`We acknowledge receipt of your submissions dated July 27, 2007; September 28, 2007; October
`31, 2007; December 4, 2007; December 17, 2007; January 18, 2008; January 24, 2008; and
`January 25, 2008.
`
`The July 27, 2007 submission constituted a complete response to our May 3, 2007 action letter.
`
`This new drug application provides for the use of Emend (fosaprepitant dimeglumine) for
`Injection, 115 mg for:
`e the prevention of acute and delayed nausea and vomiting associated with initial and
`repeat courses of highly emetogenic cancer chemotherapy, including high-dose cisplatin.
`e the prevention of nausea and vomiting associated with initial and repeat courses of
`moderately emetogenic cancer chemotherapy.
`
`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.
`
`CONTENT OF LABELING
`
`As soon as possible, but no later than 14 days from the date of this letter, please submit the
`content of labeling [21 CFR 314.50(1)] in structured product labeling (SPL) format as described
`at http://www.fda.gov/oc/datacouncil/spl.html that is identical to the enclosed labeling (text for
`the package insert, text for the patient package insert). Upon receipt, we will transmit that
`version to the National Library of Medicine for public dissemination. For administrative
`purposes, please designate this submission, “SPL for approved NDA 22-023.”
`
`Page 2 of 6
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`NDA 22-023
`Page 2
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`CARTON AND IMMEDIATE CONTAINER LABELS
`
`Submit final printed carton and container labels that are identical to the submitted carton and
`immediate container labels dated January 25, 2008 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 titled Providing Regulatory Submissions in Electronic Format — Human
`Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications
`(October 2005). 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 22-023.”
`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 drug.
`
`PEDIATRIC RESEARCH EQUITY ACT (PREA)
`
`All applications for new active ingredients, new dosage forms, new indications, new routes of
`administration, and new dosing regimens are required to contain an assessment of the safety and
`effectiveness of the product in pediatric patients unless this requirement is waived or deferred.
`We are waiving the pediatric study requirement for ages 0 months to <6 months because the
`necessary studies are impossible of highly impracticable because the number of pediatric cancer
`patients in this age group is so small. We are deferring pediatric studies for ages 6 months to 17
`years for this application because adult studies have just been completed and additional
`pharmacokinetic information is needed.
`
`Your deferred pediatric studies required under section 2 of the Pediatric Research Equity Act
`(PREA) are considered required postmarketing study commitments. The status of this
`postmarketing study shall be reported annually according to 21 CFR 314.81. This commitment is
`listed below.
`
`1. A study in adolescents and younger pediatric patients receiving emetogenic chemotherapy
`(HEC or MEC) to evaluate fosaprepitant PK, safety, and tolerability.
`
`Study Start Date: December 31, 2008
`Study Completion Date: March 31, 2011
`Final Report Submission: June 30, 2011
`
`Submit final study reports to this NDA. For administrative purposes, all submissions related to
`
`this pediatric postmarketing study commitment must be clearly designated “Required Pediatric
`Study Commitments”.
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`Page 3 of 6
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`NDA 22-023
`Page 3
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`POSTMARKETING COMMITMENTS
`
`We remind you of your postmarketing study commitment in your submission dated January 24,
`2008. This commitment is listed below.
`
`2. Further characterize the effects of fosaprepitant on blood pressure.
`Statistical Plan Submission: by April 30, 2008
`Study Start: by April 30, 2008
`Final Report Submission: by July 31, 2008
`
`Submit clinical protocols to your IND for this product. Submit nonclinical and chemistry,
`manufacturing, and controls protocols and all study final reports to this NDA. In addition,
`under 21 CFR 314.81(b)(2)(vii) and 314.81(b)(2)(viii), you should include a status summary
`of each commitment 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, number of patients entered into each study.
`All submissions, including supplements, relating to these postmarketing study commitments
`should be prominently labeled “Postmarketing Study Commitment Protocol”,
`“Postmarketing Study Commitment Final Report”, or “Postmarketing Study
`Commitment Correspondence.”
`
`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(s)
`to:
`
`Food and Drug Administration
`
`Center for Drug Evaluation and Research
`
`Division of Drug Marketing, Advertising, and Communications
`5901-B Ammendale Road
`
`Beltsville, MD 20705-1266
`
`As required under 21 CFR 314.81(b)(3)(i), you must submit final promotional materials, and the
`package insert(s), at the time of initial dissemination or publication, accompanied by a Form
`FDA 2253. For instruction on completing the Form FDA 2253, see page 2 of the Form. For
`more information about submission of promotional materials to the Division of Drug Marketing,
`Adpvertising, and Communications (DDMAC), see www.fda.gov/cder/ddmac.
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`Page 4 of 6
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`NDA 22-023
`Page 4
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`LETTERS TO HEALTH CARE PROFESSIONALS
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`If you issue a letter communicating important safety related information about this drug product
`(i.e., a “Dear Health Care Professional” letter), we request that you submit an electronic copy of
`the letter to both this NDA and to the following address:
`
`MedWatch
`
`Food and Drug Administration
`HFD-001, Suite 5100
`
`5515 Security Lane
`
`Rockville, MD 20852
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`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, call Jagjit Grewal, Regulatory Project Manager, at (301) 796-0846.
`
`Sincerely,
`{See appended electronic signature page}
`
`Joyce Korvick, M.D., MPH
`
`Deputy Division Director
`
`Division of Gastroenterology Products
`Office of Drug Evaluation III
`
`Center for Drug Evaluation and Research
`
`Enclosure: Package Insert
`Patient Package Insert
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`Page 5 of 6
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`This is a representation of an electronic record that was signed elcctrenieally and
`this page is the manifestation of the electronic signature.
`
`/s/
`
`Joyce Korvick
`1/25/2008 06:45:02 PM
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`Page 6 of 6
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