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` NDA 205552/S-029
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` NDA 210563/S-004
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` SUPPLEMENT APPROVAL
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`FULFILLMENT OF POST MARKETING REQUIREMENT
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` Pharmacyclics LLC
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` Attention: Preeti Sarde
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` Manager, Regulatory Affairs
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` 999 East Arques Avenue
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` Sunnyvale, CA 94085-4521
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` Dear Ms. Sarde:
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`Please refer to your supplemental new drug applications (sNDAs) dated May 24, 2019,
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`received May 24, 2019, and your amendments, submitted under section 505(b) of the
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`Federal Food, Drug, and Cosmetic Act (FDCA) for IMBRUVICA (ibrutinib) capsules and
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`tablets.
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`These Prior Approval supplemental new drug applications provide for updates to the
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`United States Prescribing Information Adverse Reactions section with long-term safety
`data from the final report for PMR 3038-01, entitled “Assessment of Safety Risks with
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`Long-term use of IMBRUVICA® (Ibrutinib): A Post Marketing Requirement.”
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`APPROVAL & LABELING
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` We have completed our review of this application, as amended. It is approved, effective
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` on the date of this letter, for use as recommended in the enclosed agreed-upon
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` labeling.
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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
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`content of labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using
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`the FDA automated drug registration and listing system (eLIST), as described at
`FDA.gov.1 Content of labeling must be identical to the enclosed labeling (text for the
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`Prescribing Information), with the addition of any labeling changes in pending “Changes
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`Being Effected” (CBE) supplements, as well as annual reportable changes not included
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`in the enclosed labeling.
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` 1 http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm
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`Reference ID: 4523408
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` NDA 205552/S-029
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` NDA 210563/S-004
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` Page 2
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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 from 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 NDA, including CBE supplements for which FDA has not yet issued an
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`action letter, with the content of labeling [21 CFR 314.50(l)(1)(i)] in Microsoft Word
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`format, that includes the changes approved in this supplemental application, as well as
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`annual reportable changes. To facilitate review of your submission(s), provide a
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`highlighted or marked-up copy that shows all changes, as well as a clean Microsoft
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`Word version. The marked-up copy should provide appropriate annotations, including
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`supplement number(s) and annual report date(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 indication in pediatric patients unless this requirement is waived, deferred,
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`or inapplicable.
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`Because none of these criteria apply to your application, you are exempt from this
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`requirement.
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`FULFILLMENT OF POSTMARKETING REQUIREMENT(S)/COMMITMENT(S)
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`We have received your submission dated May 24, 2019, containing the final report for
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`the following postmarketing requirement listed in March 4, 2016 (NDA 205552) approval
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`letter.
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`PMR 3038-1 Conduct a study to characterize the safety of long-term exposure to
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`Imbruvica based on data and pooled analyses from trials of patients
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`with mantle cell lymphoma and chronic lymphocytic leukemia. Submit
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`3-year, 4-year, and 5-year safety follow-up data and reports for a
`minimum population of 1000 patients treated with approved ibrutinib
`dosing regimens. Datasets should include patient-level data on
`ibrutinib dosing, treatment-emergent adverse events, and treatment-
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`emergent laboratory information. This patient set may include
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`approximately 350 patients who continue receiving long-term ibrutinib
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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 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: 4523408
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` NDA 205552/S-029
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` NDA 210563/S-004
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` Page 3
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` therapy after completion of primary analysis of the parent study,
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` where study procedures are then limited to collect a minimum of
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` Grade 3+ adverse events, available treatment emergent laboratory
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` data, adverse events leading to treatment discontinuation and SAEs.
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` Study reports should include analyses of adverse event categories
` listed in the current Warnings and Precautions section of the
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` prescribing information, adverse events leading to treatment
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` discontinuation, and serious adverse events.
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`We have reviewed your submission and conclude that the above requirement was
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`fulfilled.
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`This completes all of your postmarketing requirements and postmarketing commitments
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`acknowledged in our March 4, 2016 (NDA 205552) letter.
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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
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`requesting advisory comments, (2) the proposed materials in draft or mock-up form with
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`annotated references, and (3) the Prescribing Information 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
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`format. For more information about submitting promotional materials in eCTD format,
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`see the draft guidance for industry Providing Regulatory Submissions in Electronic and
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`Non-Electronic Format-Promotional Labeling and Advertising Materials for Human
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`Prescription Drugs.3
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`You must submit final promotional materials and Prescribing Information, accompanied
`by a Form FDA 2253, at the time of initial dissemination or publication
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`[21 CFR 314.81(b)(3)(i)]. Form FDA 2253 is available at FDA.gov.4 Information and
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` 3 When final, this guidance will represent the FDA’s current thinking on this topic. For the most recent
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` version of a guidance, check the FDA guidance web page at
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` https://www.fda.gov/RegulatoryInformation/Guidances/default.htm.
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`4 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf
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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: 4523408
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` NDA 205552/S-029
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` NDA 210563/S-004
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` Page 4
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` Instructions for completing the form can be found at FDA.gov.5 For more information
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`about submission of promotional materials to the Office of Prescription Drug Promotion
`(OPDP), see FDA.gov.6
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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, contact Patricia Garvey, Lead Regulatory Project Manager,
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`at (301) 796-8493.
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`Sincerely,
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`{See appended electronic signature page}
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`Ann T. Farrell, MD
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`Director
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`Division of Hematology Products
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`Office of Drug Evaluation I
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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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`o Prescribing Information
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` 5 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf
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` 6 http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.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: 4523408
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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/
`------------------------------------------------------------
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`ANN T FARRELL
`11/21/2019 05:50:07 PM
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`Reference ID: 4523408
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