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`ADMINISTRATION
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` NDA 216387/Original 2
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`ACCELERATED APPROVAL
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` AstraZeneca UK Limited
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` c/o AstraZeneca Pharmaceuticals LP
` Attention: Vanessa Yu, PhD
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` Regulatory Affairs Director
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` One MedImmune Way
` Gaithersburg, MD 20878
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`Dear Dr. Yu:
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`Please refer to your new drug application (NDA) dated and received October 4, 2021,
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`and your amendments, submitted under section 505(b) of the Federal Food, Drug, and
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`Cosmetic Act (FDCA) for Calquence (acalabrutinib) tablets.
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`NDA 216387 provides for the use of Calquence (acalabrutinib) tablets for the following
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`indications which, for administrative purposes, we have designated as follows:
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`• NDA 216387/Original 1 – treatment of adult patients with chronic
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`lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)
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`• NDA 216387/Original 2 – treatment of adult patients with mantle cell
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`lymphoma (MCL) who have received at least one prior therapy
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`The subject of this action letter is NDA 216387/Original 2. A separate action letter will
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`be issued for NDA 216387/Original 1.
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`APPROVAL & LABELING
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`We have completed our review of this application, as amended. It is approved under the
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`provisions of accelerated approval regulations (21 CFR 314.500), effective on the date
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`of this letter, for use as recommended in the enclosed agreed-upon labeling.
`Marketing of this drug product and related activities must adhere to the substance and
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`procedures of the referenced accelerated approval regulations.
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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
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`Highlights of Prescribing Information. This waiver applies to all future supplements
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`containing revised labeling unless we notify you otherwise.
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`Reference ID: 5024989
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` NDA 216387/Original 2
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` 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
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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 (Prescribing
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`Information, text for the Patient Package Insert). Information on submitting SPL files
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`using eLIST may be found in the guidance for industry SPL Standard for Content of
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`Labeling Technical Qs and As.2
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`The SPL will be accessible via publicly available labeling repositories.
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`CARTON AND CONTAINER LABELING
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`Submit final printed carton and container labeling that are identical to the enclosed
`carton and container labeling submitted on August 3, 2022, as soon as they are
`available, but no more than 30 days after they are printed. Please submit these labeling
`electronically according to the guidance for industry titled Providing Regulatory
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`Submissions in Electronic Format — Certain Human Pharmaceutical Product
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`Applications and Related Submissions Using the eCTD Specifications (April 2018,
`Revision 5). For administrative purposes, designate this submission “Final Printed
`Carton and Container Labeling for approved NDA 216387.” Approval of this
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`submission by FDA is not required before the labeling is used.
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`DATING PERIOD
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`Based on the stability data submitted to date, the expiry dating period for Calquence
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`(acalabrutinib) tablets shall be 24 months from the date of manufacture when stored at
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`20-25°C.
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`ACCELERATED APPROVAL REQUIREMENTS
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`Products approved under the accelerated approval regulations, 21 CFR 314.510,
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`require further adequate and well-controlled clinical trials to verify and describe clinical
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`benefit. You are required to conduct such clinical trials with due diligence. If
`postmarketing clinical trials fail to verify clinical benefit or are not conducted with due
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`diligence, we may, following a hearing in accordance with 21 CFR 314.530, withdraw
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`this approval. We remind you of your postmarketing requirement specified in your
`submission dated July 20, 2022. This requirement, along with required completion
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`dates, is listed below.
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` 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
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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: 5024989
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` NDA 216387/Original 2
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` Page 3
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`4311-1 Complete a randomized, double-blind, placebo-controlled clinical trial of
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`acalabrutinib in combination with standard immunochemotherapy versus
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`immunochemotherapy alone in patients with mantle cell lymphoma to
`obtain data on clinical efficacy and safety.
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`10/2023
`Trial Completion:
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`Final Report Submission: 11/2024
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` Submit clinical protocols to your IND 118717 for this product. In addition, under
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` 21 CFR 314.81(b)(2)(vii) and 314.81(b)(2)(viii) you should include a status summary of
` each requirement in your annual report to this NDA. The status summary should include
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` expected summary completion and final report submission dates, any changes in plans
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` since the last annual report, and, for clinical studies/trials, number of subjects entered
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` into each study/trial.
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` Submit final reports to this NDA as a supplemental application. For administrative
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` purposes, all submissions relating to this postmarketing requirement must be clearly
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` designated “Subpart H Postmarketing Requirement(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
` 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
` the claimed indication in pediatric patients unless this requirement is waived, deferred,
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` or inapplicable.
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` We are waiving the pediatric study requirement for this application because necessary
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` studies are impossible or highly impracticable.
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` PROMOTIONAL MATERIALS
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`Under 21 CFR 314.550, you are required to submit, during the application pre-approval
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`review period, all promotional materials, including promotional labeling and
` advertisements, that you intend to use in the first 120 days following marketing approval
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` (i.e., your launch campaign). If you have not already met this requirement, you must
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` immediately contact the Office of Prescription Drug Promotion (OPDP) at
` (301) 796-1200. Please ask to speak to a regulatory project manager or the appropriate
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` reviewer to discuss this issue.
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`As further required by 21 CFR 314.550, submit all promotional materials that you intend
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`to use after the 120 days following marketing approval (i.e., your post-launch materials)
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`at least 30 days before the intended time of initial dissemination of labeling or initial
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`publication of the advertisement. We ask that each submission include a detailed cover
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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: 5024989
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` NDA 216387/Original 2
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` Page 4
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`letter together with three copies each of the promotional materials, annotated
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`references, and approved Prescribing Information, Medication Guide, and Patient
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`Package Insert (as applicable).
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` For information about submitting promotional materials, see the final guidance for
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` industry Providing Regulatory Submissions in Electronic and Non-Electronic Format-
` Promotional Labeling and Advertising Materials for Human Prescription Drugs.3
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`REPORTING REQUIREMENTS
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`We remind you that you must comply with the reporting requirements for an approved
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`NDA (21 CFR 314.80 and 314.81).
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`If you have any questions, please contact Denise Felluca, Regulatory Project Manager
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`via email at denise.felluca@fda.hhs.gov or at 301-796-4574.
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`Sincerely,
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`{See appended electronic signature page}
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`Nicole J. Gormley, MD
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`Director
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`Division of Hematologic Malignancies II
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`Office of Oncologic Diseases
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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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`o Prescribing Information
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`o Patient Package Insert
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`• Carton and Container Labeling
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` 3 https://www.fda.gov/media/128163/download.
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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: 5024989
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`Signature Page 1 of 1
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`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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`NICOLE J GORMLEY
`08/04/2022 04:50:09 PM
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`Reference ID: 5024989
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