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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 205552/S-002
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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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` POST MARKETING FULFILLMENT
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`Pharmacyclics, Inc.
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`Attention: Christine Salido
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`Executive Director, Regulatory Affairs
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`995 East Arques Avenue
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`Sunnyvale, CA 94085-4521
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`Dear Ms. Salido:
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`Please refer to your Supplemental New Drug Application (sNDA) dated October 17, 2014,
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`received October 17, 2014, submitted under section 505(b) of the Federal Food, Drug, and
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`Cosmetic Act (FDCA) for Imbruvica® (ibrutinib) capsules/140mg.
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`We acknowledge receipt of your amendments dated October 30; November 3, 7, 20, and 24 (2);
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`December 2, 15, 22, and 23, 2014; and January 7 and 20, 2015.
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`This Prior Approval supplemental new drug application provides for a new indication for the
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`treatment of patients with Waldenström’s macroglobulinemia and fulfillment of the
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`postmarketing requirement trial, PMR 2060-5, “An Open-Label, Multicenter, Pharmacokinetic,
`Study of PCI-3265in Subjects with Varying Degrees of Hepatic Impairment”.
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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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`automated drug registration and listing system (eLIST), as described at
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`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content
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`of labeling must be identical to the enclosed labeling (text for the package insert), with the
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`addition of any labeling changes in pending “Changes Being Effected” (CBE) supplements, as
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`well as annual reportable changes not included in the enclosed labeling.
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`Reference ID: 3694103
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` NDA 205552/S-002
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` Page 2
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` Information on submitting SPL files using eList may be found in the guidance for industry titled
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` “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 includes 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
`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 new
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`active ingredients, new indications, new dosage forms, new dosing regimens, or new routes of
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`administration are required to contain an assessment of the safety and effectiveness of the
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`product for the claimed indication(s) in pediatric patients unless this requirement is waived,
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`deferred, or inapplicable.
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`Because this drug product for this indication has an orphan drug designation, you are exempt
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`from this requirement.
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`POSTMARKETING COMMITMENTS SUBJECT TO REPORTING REQUIREMENTS
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`UNDER SECTION 506B
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`We remind you of your postmarketing commitment:
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`2867-1
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`Develop and test the stability of a lower (35 or 70 mg) strength ibrutinib capsule
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`in order to allow dose reductions for patients with moderate hepatic impairment
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`for whom ibrutinib treatment is currently not recommended. The lower strength
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`capsule should be sufficiently distinguishable from the 140 mg capsule.
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`The timetable you submitted on January 23, 2015, states that you will conduct this study
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`according to the following schedule:
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`Final Protocol Submission: 09/2015
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`12/2016
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`Study Completion:
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`Final Report Submission:
`03/2017
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`Reference ID: 3694103
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` NDA 205552/S-002
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` Page 3
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` Submit clinical protocols to your IND 102688 for this product. Submit nonclinical and
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` chemistry, manufacturing, and controls protocols and all postmarketing final reports to this
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` NDA. In addition, under 21 CFR 314.81(b)(2)(vii) and 314.81(b)(2)(viii) you should include a
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` status summary of each commitment in your annual report to this NDA. The status summary
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` should include expected summary completion and final report submission dates, any changes in
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` plans since the last annual report, and, for clinical studies/trials, number of patients entered into
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` each study/trial. All submissions, including supplements, relating to these postmarketing
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`commitments should be prominently labeled “Postmarketing Commitment Protocol,”
`“Postmarketing Commitment Final Report,” or “Postmarketing Commitment
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`Correspondence.”
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` FULFILLMENT OF POSTMARKETING REQUIREMENT UNDER 505(o)
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`We have received your submission dated September 30, 2014, containing the final report for the
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`following postmarketing requirement listed in the November 13, 2013 approval letter.
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`PMR 2060-5 Evaluate the effect of hepatic impairment on ibrutinib pharmacokinetics. Submit
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`the final report for trial PCI -32765CLL1006 entitled, “An Open-Label,
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`Multicenter, Pharmacokinetic, Study of PCI-3265in Subjects with Varying
`Degrees of Hepatic Impairment.”
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`The timetable you submitted on November 13, 2013 states that you will conduct this study
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`according to the following schedule:
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`Final Protocol Submission: Completed 11/2012
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`Trial Completion:
`06/2014
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`Final Report Submission:
`12/2014
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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 requirements and a postmarketing commitment
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`listed in the November 13, 2013 approval letter that are still open.
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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
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`(3) the package insert(s) to:
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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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`Reference ID: 3694103
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` NDA 205552/S-002
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` Page 4
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` You must submit final promotional materials and package insert(s), accompanied by a Form
` 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 Alycia Anderson, Regulatory Project Manager, at
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`(240) 402-4270.
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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 Hematology and Oncology Products
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`Center for Drug Evaluation and Research
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`ENCLOSURE(S):
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`Content of Labeling
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`Reference ID: 3694103
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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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`ANN T FARRELL
`01/29/2015
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`Reference ID: 3694103
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