`NDA 210563/S-006
`
`
`
`SUPPLEMENT APPROVAL
`
`
`Pharmacyclics LLC
`Attention: Preeti Sarde
`Manager, Regulatory Affairs
`999 East Arques Avenue
`Sunnyvale, CA 94085-4521
`
`
`
`Dear Ms. Sarde:
`
`Please refer to your supplemental new drug applications (sNDAs) dated
`November 7, 2019, received November 7, 2019, and your amendments, submitted
`under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for
`Imbruvica® (ibrutinib) capsules and tablets, for NDA 205552/S-030 and
`NDA 210563/S-006, respectively.
`
`These Prior Approval supplemental new drug applications provide for labeling updates
`to add efficacy and safety data from the E1912 study (A Randomized Phase III Study of
`Ibrutinib based Therapy vs Standard Fludarabine, Cyclophosphamide, and Rituximab
`[FCR] Chemoimmunotherapy in Untreated Younger Patients with Chronic Lymphocytic
`Leukemia [CLL]) to expand ibrutinib in combination with rituximab for adult patients with
`chronic lymphocytic leukemia or small lymphocytic lymphoma (SLL).
`
`APPROVAL & LABELING
`
`We have completed our review of these applications, as amended. It is approved,
`effective on the date of this letter, for use as recommended in the enclosed agreed-
`upon labeling.
`
`WAIVER OF ½ PAGE LENGTH REQUIREMENT FOR HIGHLIGHTS
`
`Please note that we have previously granted a waiver of the requirements of 21 CFR
`201.57(d)(8) regarding the length of Highlights of Prescribing Information.
`
`
`Reference ID: 4595561
`
`
`
`NDA 205552/S-030
`NDA 210563/S-006
`Page 2
`
`
`CONTENT OF LABELING
`
`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
`FDA.gov.1 Content of labeling must be identical to the enclosed labeling (text for the
`Prescribing Information and Patient Package Insert), 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 SPL Standard for Content of Labeling Technical Qs and As.2
`
`
`The SPL will be accessible from publicly available labeling repositories.
`
`Also within 14 days, amend all pending supplemental applications that include 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 Microsoft Word
`format, that includes the changes approved in this supplemental application, as well as
`annual reportable changes. To facilitate review of your submission(s), 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).
`
`
`REQUIRED PEDIATRIC ASSESSMENTS
`
`Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for
`new active ingredients (which includes new salts and new fixed combinations), 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 in pediatric patients unless this requirement is waived, deferred,
`or inapplicable.
`
`Because this drug product for this indication has an orphan drug designation, you are
`exempt from this requirement.
`
`
`
`
`
` 1 http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm
`2 We update guidances periodically. For the most recent version of a guidance, check the FDA Guidance
`Documents Database https://www.fda.gov/RegulatoryInformation/Guidances/default.htm.
`
`U.S. Food and Drug Administration
`
`
`Silver Spring, MD 20993
`
`www.fda.gov
`
`Reference ID: 4595561
`
`
`
`NDA 205552/S-030
`NDA 210563/S-006
`Page 3
`
`
`POSTMARKETING COMMITMENTS SUBJECT TO REPORTING REQUIREMENTS
`UNDER SECTION 506B
`
`We remind you of your postmarketing commitments:
`
`
`NDA 205552/S-030
`
`
`3811-1 Submit the overall survival analysis and datasets with the final report for
`clinical trial E1912 titled, “A Randomized Phase III Study of Ibrutinib-
`Based Therapy vs Standard Fludarabine, Cyclophosphamide, and
`
`Rituximab Chemoimmunotherapy in Untreated Younger Patients with
`Chronic Lymphocytic Leukemia” to provide additional long term efficacy
`data.
`
`
`
`NDA 210563/S-006
`
`
`3836-1 Submit the overall survival analysis and datasets with the final report for
`clinical trial E1912 titled, “A Randomized Phase III Study of Ibrutinib-
`Based Therapy vs Standard Fludarabine, Cyclophosphamide, and
`
`Rituximab Chemoimmunotherapy in Untreated Younger Patients with
`Chronic Lymphocytic Leukemia” to provide additional long term efficacy
`data.
`
`
`The timetable you submitted on April 10, 2020 states that you will conduct this study
`according to the following schedule:
`
`
`Final Protocol Submission: 05/2019 (completed)
`
`Trial Completion:
`09/2026
`Final Report Submission: 09/2027
`
`A final submitted protocol is one that the FDA has reviewed and commented upon, and
`you have revised as needed to meet the goal of the study or clinical trial.
`
`Submit clinical protocols to your IND 102688 for this product. Submit nonclinical and
`chemistry, manufacturing, and controls protocols and all postmarketing 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/trials, number of patients entered into each study/trial. All submissions, including
`supplements, relating to these postmarketing commitments should be prominently
`labeled “Postmarketing Commitment Protocol,” “Postmarketing Commitment Final
`
`
`Report,” or “Postmarketing Commitment Correspondence.”
`
`U.S. Food and Drug Administration
`
`
`Silver Spring, MD 20993
`www.fda.gov
`
`
`Reference ID: 4595561
`
`
`
`NDA 205552/S-030
`NDA 210563/S-006
`Page 4
`
`
`PROMOTIONAL MATERIALS
`
`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 Prescribing Information to:
`
`
`OPDP Regulatory Project Manager
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion (OPDP)
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
`
`
`Alternatively, you may submit a request for advisory comments electronically in eCTD
`format. For more information about submitting promotional materials in eCTD format,
`see the draft guidance for industry Providing Regulatory Submissions in Electronic and
`Non-Electronic Format-Promotional Labeling and Advertising Materials for Human
`
`Prescription Drugs.3
`
`You must submit final promotional materials and Prescribing Information, accompanied
`by a Form FDA 2253, at the time of initial dissemination or publication
`[21 CFR 314.81(b)(3)(i)]. Form FDA 2253 is available at FDA.gov.4 Information and
`Instructions for completing the form can be found at FDA.gov.5 For more information
`about submission of promotional materials to the Office of Prescription Drug Promotion
`(OPDP), see FDA.gov.6
`
`
`REPORTING REQUIREMENTS
`
`
`We remind you that you must comply with reporting requirements for an approved NDA
`(21 CFR 314.80 and 314.81).
`
`
`
`
`
`
`
`3 When final, this guidance will represent the FDA’s current thinking on this topic. For the most recent
`version of a guidance, check the FDA guidance web page at
`https://www.fda.gov/RegulatoryInformation/Guidances/default.htm.
`
`4 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf
`
`
`5 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf
`
`
`6 http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm
`
`
`U.S. Food and Drug Administration
`
`
`Silver Spring, MD 20993
`www.fda.gov
`
`
`Reference ID: 4595561
`
`
`
`NDA 205552/S-030
`NDA 210563/S-006
`Page 5
`
`
`If you have any questions, call Laura Wall, Senior Regulatory Project Manager, at
`
`301-796-2237.
`
`
`Sincerely,
`
`{See appended electronic signature page}
`
`
` Nicole Gormley, MD
`
`Director (Acting)
`Division of Hematologic Malignancies II
`Office of Oncologic Diseases
`Center for Drug Evaluation and Research
`(CDER)
`
`
`
`ENCLOSURES:
`
` Content of Labeling
`
`o Prescribing Information
`
`o Patient Package Insert
`
`
`
`
`
`
`
`U.S. Food and Drug Administration
`
`
`Silver Spring, MD 20993
`www.fda.gov
`
`
`Reference ID: 4595561
`
`
`
`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/
`------------------------------------------------------------
`
`NICOLE J GORMLEY
`04/21/2020 12:44:54 PM
`
`Reference ID: 4595561
`
`(
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`
`
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