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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 021992/S-033/S-036
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` SUPPLEMENT APPROVAL
`FULFILLMENT OF POSTMARKETING
`REQUIREMENT
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`Wyeth Pharmaceuticals, Inc., a subsidiary of Pfizer
`Attention: Maria A. Pias
`Associate Director
`Worldwide Regulatory Strategy, Pfizer
`PO Box 8299
`Philadelphia, PA 19101-8299
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`Dear Ms. Pias:
`
`Please refer to the following Supplemental New Drug Applications (sNDA) submitted under
`section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for Pristiq (desvenlafaxine)
`50 mg, 100 mg Extended-Release Tablets:
`
`
` S-033, dated April 16, 2012, received April 17, 2012, a “Prior Approval” supplemental new
`drug application that proposes to add data in support of a new indication in adults for
`desvenlafaxine SR for the maintenance treatment of Major Depressive Disorder (MDD) and
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` S-036, dated November 12, 2012 and received November 13, 2012, a “Changes Being
`Affected” supplemental new drug application that provides safety data updates to Section 6
`Adverse Reactions.
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`October 16, 2012
`November 5, 2012
`November 21, 2012
`December 18, 2012
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`January 25, 2013
`February 8, 2013
`February 14, 2013
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`We acknowledge receipt of your amendments dated:
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`May 31, 2012
`June 22, 2012
`July 12, 2012
`September 7, 2012
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`We have completed our review of these supplemental applications, as amended. They are
`approved, effective on the date of this letter, for use as recommended in the enclosed, agreed-
`upon labeling text.
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`We note that your April 17, 2012 submission includes final printed labeling (FPL) for your
`package insert and Medication Guide. We have not reviewed this FPL. You are responsible for
`assuring that the wording in this printed labeling is identical to that of the approved content of
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`labeling in the structured product labeling (SPL) format.
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`Reference ID: 3261674
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`

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` NDA 021992/S-033/S-036
`Page 2
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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 (package insert and Medication Guide),
`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.
`
`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 includes 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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`FULFILLMENT OF POSTMARKETING REQUIREMENT(S)/COMMITMENT(S)
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`We have received your submission dated April 16, 2012, containing the final report for the
`following postmarketing requirement listed in the February 29, 2008 approval letter.
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`1229-3
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`Although your NDA for desvenlafaxine succinate demonstrates effectiveness of
`recommended doses (50-100 mg/day) as a treatment for Major Depressive
`Disorder over an interval of 8 weeks, it does not provide information about the
`duration and conditions of treatment with desvenlafaxine that are necessary to
`sustain its antidepressant effects over the full duration (likely 6 months to a year
`or longer) of an acute major depressive episode at these same recommended
`doses. While it is widely assumed that continued treatment of symptomatically
`remitted patients reduces their risk of relapse, [...] we have no evidence that
`desvenlafaxine at these lower doses has efficacy after 8 weeks. Once you have
`established the lower end of the dose-response curve for efficacy, you have
`agreed to conduct and submit the results of a randomized withdrawal study to
`address longer-term efficacy for your drug at appropriate doses. If the lower dose
`study establishes that 50 mg/day is the lowest effective dose, this study will
`evaluate doses of 50 and 100 mg/day. You have agreed to submit the results of
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`Reference ID: 3261674
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`

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` NDA 021992/S-033/S-036
`Page 3
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`this trial no later than 3 years after the date of initiation, or approximately 5.5
`years from the date of approval for this NDA.
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` We have reviewed your submission and conclude that the above requirement was fulfilled.
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`We remind you that there are postmarketing commitments listed in the February 29, 2008
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`approval letter that are still open.
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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, 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 acknowledge your submission, dated January 24, 2013, proposing to waive the pediatric
`study requirement for ages 0 to 6 years and defer the studies for the 7 to 17 years.
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`We are waiving the pediatric study requirement for ages 0 to 6 years because necessary studies
`are impossible or highly impracticable. MDD cannot be reliably diagnosed in this age group.
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`We are deferring submission of your pediatric studies for the maintenance treatment of MDD for
`ages 7-17 years (children and adolescents) until the data for PMC 1229-1 is received and
`reviewed. Your deferred pediatric studies required by section 505B(a) of the Federal Food, Drug,
`and Cosmetic Act are required postmarketing studies. The status of this/these postmarketing
`studies must be reported annually according to 21 CFR 314.81(FOR NDAs)/21 CFR
`601.70(FOR BLAs) and section 505B(a)(3)(B) of the Federal Food, Drug, and Cosmetic Act.
`Until PMC 1229-1 is fulfilled, the deferred pediatric study will need to meet the following
`deadlines:
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` Deferred pediatric study under PREA for the maintenance treatment of Major Depressive
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` Disorder (MDD) in subjects age 7 to 17 years
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`
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`Protocol Submission Date: June 30, 2018
`Study Completion Date: December 31, 2024
`Final Report Submission: June 25, 2025
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`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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`Reference ID: 3261674
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`

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` NDA 021992/S-033/S-036
`Page 4
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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 package insert(s) to:
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`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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`You must submit final promotional materials and package insert(s), accompanied by a Form
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`FDA 2253, at the time of initial dissemination or publication [21 CFR 314.81(b)(3)(i)]. Form
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`FDA 2253 is available at http://www.fda.gov/opacom/morechoices/fdaforms/cder.html;
`instructions are provided on page 2 of the form. 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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`If you have any questions, email Juliette Touré, PharmD, Senior Regulatory Project Manager, at
`Juliette.Toure@fda.hhs.gov.
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`Sincerely,
`
`{See appended electronic signature page}
`
`
`Mitchell V. Mathis, M.D.
`CAPT, USPHS
`Director (acting)
`Division of Psychiatry Products
`Office of Drug Evaluation I
`Center for Drug Evaluation and Research
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`ENCLOSURE:
`Content of Labeling
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`Reference ID: 3261674
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`

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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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`MITCHELL V Mathis
`02/14/2013
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`Reference ID: 3261674
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