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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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` SUPPLEMENT APPROVAL
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` FULFILLMENT OF POSTMARKETING REQUIREMENT
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` REMS ASSESSMENT ACKNOWLEDGEMENT
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`RELEASE REMS REQUIREMENT
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` NDA 021928/S-040
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` Pfizer, Inc.
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` 235 E. 42nd Street
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` New York, NY 10017
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`Attention:
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`Lilya I. Donohew, PhD
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`Senior Director, Worldwide Regulatory Affairs
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`Dear Dr. Donohew:
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`Please refer to your Supplemental New Drug Application (sNDA) dated and received February
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`18, 2016, and your amendments, submitted under section 505(b) of the Federal Food, Drug, and
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`Cosmetic Act (FDCA) for Chantix (varenicline) Tablets; 0.5 mg and 1 mg.
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`We also refer to our electronic communication dated December 1, 2016; and we acknowledge
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`receipt of your risk evaluation and mitigation strategy (REMS) assessment dated October 14,
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`2016. After consultation between the Office of Surveillance and Epidemiology and the Office of
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`New Drugs, we found the REMS assessment to be complete.
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`This Prior Approval sNDA proposes changes to the package insert based on clinical trial data
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`from the study titled, “A Phase 4, Randomized, Double-Blind, Active and Placebo-Controlled,
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`Multicenter Study Evaluating the Neuropsychiatric Safety and Efficacy of 12 Weeks Varenicline
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`Tartrate 1 mg BID and Bupropion Hydrochloride 150 mg BID for Smoking Cessation in
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`Subjects with and Without a History of Psychiatric Disorders”; the supplement also proposes
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`corresponding changes to the Medication Guide, and provides for proposed modification to the
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`approved REMS for Chantix (varenicline).
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`APPROVAL & LABELING
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`We have completed our review of this supplemental application, as amended. It is approved,
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`effective on the date of this letter, for use as recommended in the enclosed, agreed-upon labeling
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`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
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`labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using the FDA
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`Reference ID: 4029004
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` NDA 021928/S-040
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` Page 2
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` automated drug registration and listing system (eLIST), as described at
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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, and Medication
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`Guide), with the addition of any labeling changes in pending “Changes Being Effected” (CBE)
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`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
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`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
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`for this NDA, including CBE supplements for which FDA has not yet issued an action letter,
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`with the content of labeling [21 CFR 314.50(l)(1)(i)] in MS Word format, that includes the
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`changes approved in this supplemental application, as well as annual reportable changes and
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`annotate each change. To facilitate review of your submission, provide a highlighted or marked-
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`up copy that shows all changes, as well as a clean Microsoft Word version. The marked-up copy
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`should provide appropriate annotations, including supplement number(s) and annual report
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`date(s).
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`We request that the labeling approved today be available on your website within 10 days of
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`receipt of this letter.
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`FULFILLMENT OF POSTMARKETING REQUIREMENT
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`We have received your submissions dated November 16, 2015, and February 18, 2016, reporting
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`on and containing the final report for the following postmarketing requirement listed in the
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`March 12, 2010, post-approval postmarketing requirements letter:
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`1544-4 A large randomized, double-blind, active- and placebo-controlled trial to compare the
`risk of clinically significant neuropsychiatric events, including but not limited to
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`suicidality, in individuals using Chantix (varenicline), bupropion, nicotine replacement
`therapy, or placebo as aids to smoking cessation over 12 weeks of treatment, and to
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`determine whether individuals with prior history of psychiatric disorders are at greater
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`risk for development of clinically significant neuropsychiatric events compared to
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`individuals without prior history of psychiatric disorders while using Chantix
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`(varenicline) as an aid to smoking cessation. The trial should be sufficiently powered
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`to adequately assess clinically significant neuropsychiatric events with each treatment
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`and in both of the two subgroups (i.e., with and without psychiatric disorders).
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`We have reviewed your submissions and conclude that the above requirement has been fulfilled.
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`We remind you that there are postmarketing requirements listed in the May 10, 2006, approval
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`Reference ID: 4029004
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` NDA 021928/S-040
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` Page 3
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` letter, and the September 22, 2011, post-approval postmarketing requirement letter that are still
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` open.
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`RISK EVALUATION AND MITIGATION STRATEGY REQUIREMENTS
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` The REMS for Chantix (varenicline) was originally approved on October 19, 2009, and the most
` recent modification was approved on August 12, 2016. The REMS consists of a Medication
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` Guide, and a timetable for submission of assessments of the REMS. Your proposed modification
` to the REMS consists of a revised Medication Guide to correspond to changes to the product
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` label.
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`In accordance with section 505-1 of the FDCA, we have determined that the following REMS
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`modification is necessary to minimize burden on the healthcare delivery system of complying
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`with the REMS:
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`• Removal of the Medication Guide as an element of the REMS
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`We have determined that maintaining the Medication Guide as part of the approved labeling is
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`adequate to address the serious and significant public health concern and meets the standard in
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`21 CFR 208. Therefore, it is no longer necessary to include the Medication Guide as an element
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`of the approved REMS to ensure that the benefits of Chantix (varenicline) outweigh its risks. The
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`Medication Guide will continue to be part of the approved labeling in accordance with 21 CFR
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`208. Like other labeling, Medication Guides are subject to the safety labeling change provisions
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`of section 505(o)(4) of the FDCA.
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`Therefore, because the Medication Guide as part of the REMS is no longer necessary to ensure
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`the benefits of the drug outweigh the risks, a REMS is no longer required for Chantix
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`(varenicline).
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`PROMOTIONAL MATERIALS
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`You may request advisory comments on proposed introductory advertising and promotional
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`labeling. To do so, submit the following, in triplicate, (1) a cover letter requesting advisory
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`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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`OPDP Regulatory Project Manager
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`Food and Drug Administration
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`Center for Drug Evaluation and Research
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`Office of Prescription Drug Promotion (OPDP)
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`5901-B Ammendale Road
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`Beltsville, MD 20705-1266
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`Alternatively, you may submit a request for advisory comments electronically in eCTD format.
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`For more information about submitting promotional materials in eCTD format, see the draft
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`Guidance for Industry (available at:
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`Reference ID: 4029004
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` NDA 021928/S-040
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` Page 4
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`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
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` CM443702.pdf ).
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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/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf.
`Information and Instructions for completing the form can be found at
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`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf. For
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`more information about submission of promotional materials to the Office of Prescription Drug
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`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
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`(21 CFR 314.80 and 314.81).
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`If you have any questions, call Ayanna Augustus, PhD, RAC, Sr. Regulatory Project Manager, at
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`(301) 796-3980.
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`Sincerely,
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`{See appended electronic signature page}
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`Sharon H. Hertz, MD
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`Director
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`Division of Anesthesia, Analgesia,
`and Addiction Products
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`Office of Drug Evaluation II
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`Center for Drug Evaluation and Research
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`Enclosure:
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`Content of Labeling
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`Reference ID: 4029004
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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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`SHARON H HERTZ
`12/16/2016
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`Reference ID: 4029004
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`