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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`NDA 205552/S-026
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`NDA 210563/S-002
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`Food and Drug Administration
`Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
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`Pharmacyclics LLC
`Attention: Tania Bekerman
`Senior Manager, Regulatory Affairs
`995 East Arques Avenue
`Sunnyvale, CA 94085-4521
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`Dear Ms. Bekerman:
`
`Please refer to your Supplemental New Drug Applications (sNDAs) dated August 17, 2018, and
`August 21, 2018, respectively, received August 17, 2018, and August 21, 2018, and your
`amendments, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act
`(FDCA) for Imbruvica® (ibrutinib) capsules: 70 mg and 140 mg, and tablets: 140 mg, 280 mg,
`420 mg, and 560 mg.
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`These Prior Approval supplemental new drug applications provide for updates to Section 6
`Adverse Reactions and Section 14 Clinical Studies of the Imbruvica United States Prescribing
`Information to include:
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` Efficacy and safety data from the iLLUMINATE study in patients with treatment naïve
`chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) treated with
`Imbruvica in combination with obinutuzumab or chlorambucil in combination with
`obinutuzumab.
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` Additional follow-up data in the CLL/SLL population from the RESONATE and
`RESONATE-2 studies.
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`APPROVAL & LABELING
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`We have completed our review of this supplemental application, as amended. It is approved,
`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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`WAIVER OF ½ PAGE LENGTH REQUIREMENT FOR HIGHLIGHTS
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`We are waiving the requirements of 21 CFR 201.57(d)(8) regarding the length of Highlights of
`Prescribing Information. This waiver applies to all future supplements containing revised
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`labeling unless we notify you otherwise.
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`Reference ID: 4380999
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`

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`NDA 205552/S-026
`NDA 210563/S-002
`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
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`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 (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
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`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
`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
`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).
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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 (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.
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`Because none of these criteria apply to your application, you are exempt from this requirement.
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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 Prescribing Information to:
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`Reference ID: 4380999
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`

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`NDA 205552/S-026
`NDA 210563/S-002
`Page 3
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`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
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`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 (available at:
`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
`CM443702.pdf ).
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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 [21 CFR 314.81(b)(3)(i)].
`Form 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
`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf. 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, call Jennifer Lee, Regulatory Project Manager, at (240) 402-4622.
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`Sincerely,
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`{See appended electronic signature page}
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`
`Albert Deisseroth, MD, PhD
`Supervisory Associate Division Director
`Division of Hematology Products
`Office of Hematology and Oncology Products
`Center for Drug Evaluation and Research
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`ENCLOSURES:
`Content of Labeling
`Prescribing Information
`Patient Package Insert
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`Reference ID: 4380999
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`

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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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`ALBERT B DEISSEROTH
`01/25/2019 10:14:15 AM
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`Reference ID: 4380999
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