CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`APPLICATION NUMBER:
`
`210563Orig1s000
`210563Orig2s000
`
`SUMMARY REVIEW
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`Division Director Summary Review for Regulatory Action
`
`R. An elo de Claro, MD
`From
`
`Division Director Summary Review
`Subject
`NDA 210563 (Type 3 NDA—New Dosage Form)
`NDA/BLA # and Supplement #
`Ori'inal-l and Ori inal-2
`
`Pharmacyclics, LLC
`Applicant
`Date of Submission
`31 Au st 2017
`
`2018
`28 Feb .
`PDUFA Goal Date
`
`Imbruvica
`Proprietary Name
`Established or Pro s er Name
`
`Ibrutinib
`
`Tablets: 140mg, 280mg, 420mg and 560mg, for oral
`Dosage Form(s)
`use
`
`Applicant Proposed
`Indication 5 [Po ulation 5
`
`Action or Recommended Action:
`Approval
`
`Same indications as capsule dosage form
`
`Approved/Recommended
`Indication(s)/Population(s) (if
`a t t licable
`
`Material Reviewed/Consulted
`
`Same indications as capsule dosage form
`
` OPQ Review
`
`0ND Action Package, including:
`Names of discipline reviewers
`Marget Merino / Tanya Wroblewski
`Medical Officer Review
`
`Statistical Review
`N/A
`
`Pharmacology Toxicology Review
`
`N/A
`Sherita McLamore (Application Technical Lead) / refer
`to CMC review for full list
`
`Microbiology Review
`N/A
`
`Clinical Pharmacology Review
`Liang Li / Olanrewaju Okusanya
`OPDP
`Nisha Patel
`
`OSI
`N/A
`
`CDTL Review
`Tanya Wroblewski
`OSE/DEPI
`N/A
`
`OSE/DMEPA
`
`OSE/DRISK
`
`N/A
`
`N/A
`
`
`
`Susan Redwood
`Other: Patient Labeling Review
`Abbreviations: 0ND=Otfice ofNew Drugs, OPQ=0fiioe of Pharmaceutical Quality, 0PDP=0flice ofPrescription Drug Promotion
`OSI=0fice of Scientific Investigations, CDTIFCross—Discipline To- Leader, 0513: Oflice of Surveillance and Epidemiology
`DEPI= Division of Epidemiology, DMEPA=Division of Medication Error Prevention and Analysis, DRISK=Division of Risk Management
`
`Reference ID: 4222487
`
`

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`NDA 210563 (Original-1 and Original-2) Imbruvica (ibrutinib) tablets
`CDER Division Director Summary Review
`
`1. Benefit-Risk Assessment
`
`The Applicant submitted a Type 3 NDA (new dosage form) to seek approval of a tablet
`dosage form with dose strengths of 140mg, 280 mg, 420mg, and 560mg. The tablets
`will have the same indications and dosing as the currently marketed ibrutinib capsules.
`The new tablet dosage forms are intended to improve pill burden and provide for
`appropriate doses with a single tablet.
`
`Imbruvica capsule dosage form (NDA 205552) has regular approval for the following
`indications:
`adult patients with chronic lymphocytic leukemia (CLL)/small lymphocytic
`
`lymphoma (SLL)
`adult patients with chronic lymphocytic leukemia (CLL)/small lymphocytic
`lymphoma (SLL) with 17p deletion
`adult patients with Waldenström’s macroglobulinemia (WM)
`adult patients with chronic graft-versus-host disease (cGVHD) after failure of one
`or more lines of systemic therapy
`
`
`
`
`
`
`Imbruvica capsule dosage form (NDA 205552) has accelerated approval for the
`following indications:
`adult patients with mantle cell lymphoma (MCL) who have received at least one
`
`prior therapy.
`adult patients with marginal zone lymphoma (MZL) who require systemic therapy
`and have received at least one prior anti-CD20-based therapy
`
`
`
`Regulatory Recommendation: Approval of NDA 210563 for the tablet dosage forms
`with dose strengths of 140 mg, 280 mg, 420 mg, and 560 mg for the same approved
`indications as for Imbruvica capsule dosage form (NDA 205552).
`
`Accelerated approval (NDA 210563 Original-2) is recommended for the mantle cell
`lymphoma and marginal zone lymphoma indications because these indications remain
`under accelerated approval under NDA 205552. Regular approval (NDA 210563
`Original-1) is recommended for all of the other indications.
`2. Background
`
`This application provides CMC and clinical pharmacology data to support stability and
`bioequivalence of a new tablet dosage form for ibrutinib. There was no new clinical
`efficacy or safety data included in this NDA and therefore no need for benefit-risk
`assessment. There are no updates to the indication, efficacy, or safety sections of the
`USPI.
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`2
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`Reference ID: 4222487
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`NDA 210563 (Original-1 and Original-2) Imbruvica (ibrutinib) tablets
`CDER Division Director Summary Review
`
`3. Product Quality
`
`From CMC Application Technical Lead Review:
`
`The Office of Pharmaceutical Quality (OPQ) recommends APPROVAL of NDA
`210563 for IMBRUVICA® (ibrutinib) Tablets, 140 mg, 280 mg, 420 mg, 560 mg. As
`part of this action, OPQ grants a 24-month expiration period for the drug product
`when stored at stored at controlled room temperature 20°C to 25°C (68°F to 77°F)
`with excursions permitted between 15°C and 30°C (between 59°F and 86°F). The
`Office of Pharmaceutical Quality has no Post-Marketing Commitments (PMCs) or
`Post-Marketing Requirements (PMRCs) to be conveyed to the applicant.
`
`No issues were identified that would preclude approval.
`
`4. Nonclinical Pharmacology/Toxicology
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`No issues were identified that would preclude approval.
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`5. Clinical Pharmacology
`
`From Clinical Pharmacology Review:
`
`The Office of Clinical Pharmacology has reviewed the information submitted. The to-
`be-marketed tablet formulation at dose strengths of 140 mg, 280 mg, 420 mg, and 560
`mg is considered approvable from a clinical pharmacology perspective. Dosing
`guidelines regarding food timings for ibrutinib tablets should follow the same
`recommendation for the ibrutinib capsules in the current labeling, i.e., there are no
`restrictions for food consumption when taking ibrutinib tablets or capsules.
`
`No issues were identified that would preclude approval.
`
`6. Clinical Microbiology
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`No issues were identified that would preclude approval.
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`7. Clinical/Statistical-Efficacy
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`No issues were identified that would preclude approval.
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`Reference ID: 4222487
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`3
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`NDA 210563 (Original-1 and Original-2) Imbruvica (ibrutinib) tablets
`CDER Division Director Summary Review
`
`8. Safety
`
`No new safety issues were identified that would preclude approval.
`
`9. Advisory Committee Meeting
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`This product is not a new molecular entity.
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`10.
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`Pediatrics
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`Ibrutinib has orphan drug designation for all of the approved indications and is thus
`exempt from pediatric study requirements described in 21 CFR 314.55.
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`11.
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`Other Relevant Regulatory Issues
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`No issues were identified that would preclude approval.
`
`12.
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`Labeling
`
`All review disciplines participated in labeling negotiations and review. Refer to CDTL
`review for summary of key labeling recommendations.
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`13.
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`Postmarketing
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` Postmarketing Risk Evaluation and Mitigation Strategies
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`Routine pharmacovigilance
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` Other Postmarketing Requirements and Commitments
`
`Existing accelerated approval PMRs 2060-2 and 3150-1 for NDA 205552 will carry
`over to this NDA. New PMR set numbers were issued for administrative purposes.
`Refer to action letter for final wording.
`
`Reference ID: 4222487
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`4
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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.
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`/s/
`----------------------------------------------------
`
`ROMEO A DE CLARO
`02/15/2018
`
`Reference ID: 4222487
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