CENTER FOR DRUG EVALUATION AND RESEARCH
`
`Approval Package for:
`
`APPLICATION NUMBER:
`
` 214120Orig1s000
`
`
`
`Trade Name:
`
` ONUREG
`
`azacitidine
`
`Generic or Proper
`Name:
`
`Sponsor:
`
`
`
`
`Approval Date:
`
`
`Indication:
`
`
`Celgene Corporation
`
`September 1, 2020
`
`For continued treatment of adult patients with acute
`myeloid leukemia who achieved first complete remission
`(CR) or complete remission with incomplete blood count
`recovery (CRi) following intensive induction
`chemotherapy and are not able to complete intensive
`curative therapy
`
`

`

`CENTER FOR DRUG EVALUATION AND RESEARCH
`
`214120Orig1s000
`
`CONTENTS
`
`Reviews / Information Included in this NDA Review.
`
`
`
`Approval Letter
`Other Action Letters
`Labeling
`REMS
`Officer/Employee List
`Multidiscipline Review(s)
`• Summary Review
`• Office Director
`• Cross Discipline Team Leader
`• Clinical
`• Non-Clinical
`• Statistical
`• Clinical Pharmacology
`Product Quality Review(s)
`Clinical Microbiology / Virology Review(s)
`Other Reviews
`Risk Assessment and Risk Mitigation Review(s)
`Proprietary Name Review(s)
`Administrative/Correspondence Document(s)
`
`
`X
`
`X
`
`X
`X
`
`X
`
`X
`
`X
`X
`
`

`

`
`
`
`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`APPLICATION NUMBER:
`
`214120Orig1s000
`
`
`APPROVAL LETTER
`
`

`

`NDA 214120
`
`
`
`NDA APPROVAL
`
`
`Celgene Corporation
`Attention: Mary Vandekauter, MS, RAC
`Director, Global Regulatory & Safety Sciences
`86 Morris Avenue
`Summit, NJ 07901
`
`
`Dear Ms. Vandekauter:
`
`Please refer to your new drug application (NDA) dated March 3, 2020, received March
`3, 2020, and your amendments, submitted under section 505(b) of the Federal Food,
`Drug, and Cosmetic Act (FDCA) for ONUREG (azacitidine) tablets.
`
`This new drug application provides for the use of ONUREG (azacitidine) tablets for
`continued treatment of adult patients with acute myeloid leukemia who achieved first
`complete remission (CR) or complete remission with incomplete blood count recovery
`(CRi) following intensive induction chemotherapy and are not able to complete intensive
`curative therapy.
`
`APPROVAL & LABELING
`
`We have completed our review of this application, as amended. It is approved, effective
`on the date of this letter, for use as recommended in the enclosed agreed-upon
`labeling.
`
`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) 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 via publicly available labeling repositories.
`
`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.
`
`
`Reference ID: 4664690
`
`

`

`NDA 214120
`Page 2
`
`
`
`CARTON AND CONTAINER LABELING
`
`Submit final printed carton and container labeling that are identical to the carton and
`container labeling submitted on August 12, 2020, 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 Providing Regulatory Submissions in Electronic
`Format — Certain Human Pharmaceutical Product Applications and Related
`Submissions Using the eCTD Specifications. For administrative purposes, designate
`this submission “Final Printed Carton and Container Labeling for approved NDA
`214120.” Approval of this submission by FDA is not required before the labeling is
`used.
`
`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.
`
`POSTMARKETING REQUIREMENTS UNDER 505(o)
`
`Section 505(o)(3) of the FDCA authorizes FDA to require holders of approved drug and
`biological product applications to conduct postmarketing studies and clinical trials for
`certain purposes, if FDA makes certain findings required by the statute.
`
`We have determined that an analysis of spontaneous postmarketing adverse events
`reported under subsection 505(k)(1) of the FDCA will not be sufficient to identify an
`unexpected serious risk of increased toxicity in patients with hepatic impairment.
`
`Furthermore, the active postmarket risk identification and analysis system as available
`under section 505(k)(3) of the FDCA will not be sufficient to assess this serious risk.
`
`Finally, we have determined that only a clinical trial (rather than a nonclinical or
`observational study) will be sufficient to identify this unexpected serious risk.
`
`Therefore, based on appropriate scientific data, FDA has determined that you are
`required to conduct the following trial:
`
`
`U.S. Food and Drug Administration
`Silver Spring, MD 20993
`www.fda.gov
`
`Reference ID: 4664690
`
`

`

`NDA 214120
`Page 3
`
`
`
`3923-1 Submit the final report and datasets from a clinical pharmacokinetic study
`to determine a safe and appropriate dose of oral azaciditine in patients
`with moderate and severe hepatic impairment that may inform product
`labeling. Design and conduct the study in accordance with the FDA
`Guidance for Industry titled; Pharmacokinetics in Patients with Impaired
`Hepatic Function: Study Design, Data Analysis, and Impact on Dosing and
`Labeling.
`
`
`The timetable you submitted on August 24, 2020, states that you will conduct this trial
`according to the following schedule:
`
`
`Draft Protocol Submission:
`Final Protocol Submission:
`Trial Completion:
`
`
`Final Report Submission:
`
`12/2020
`04/2021
`10/2025
`04/2026
`
`
`FDA considers the term final to mean that the applicant has submitted a protocol, the
`FDA review team has sent comments to the applicant, and the protocol has been
`revised as needed to meet the goal of the study or clinical trial.3
`
`Submit clinical protocol(s) to your IND 074618 with a cross-reference letter to this NDA.
`Submit nonclinical and chemistry, manufacturing, and controls protocols and all final
`report(s) to your NDA. Prominently identify the submission with the following wording in
`bold capital letters at the top of the first page of the submission, as appropriate:
`Required Postmarketing Protocol Under 505(o), Required Postmarketing Final
`Report Under 505(o), Required Postmarketing Correspondence Under 505(o).
`
`Section 505(o)(3)(E)(ii) of the FDCA requires you to report periodically on the status of
`any study or clinical trial required under this section. This section also requires you to
`periodically report to FDA on the status of any study or clinical trial otherwise
`undertaken to investigate a safety issue. Section 506B of the FDCA, as well as 21 CFR
`314.81(b)(2)(vii) requires you to report annually on the status of any postmarketing
`commitments or required studies or clinical trials.
`
`FDA will consider the submission of your annual report under section 506B and
`21 CFR 314.81(b)(2)(vii) to satisfy the periodic reporting requirement under section
`505(o)(3)(E)(ii) provided that you include the elements listed in 505(o) and
`21 CFR 314.81(b)(2)(vii). We remind you that to comply with 505(o), your annual report
`must also include a report on the status of any study or clinical trial otherwise
`undertaken to investigate a safety issue. Failure to submit an annual report for studies
`or clinical trials required under 505(o) on the date required will be considered a violation
`of FDCA section 505(o)(3)(E)(ii) and could result in enforcement action.
`
`3 See the guidance for Industry Postmarketing Studies and Clinical Trials—Implementation of Section
`505(o)(3) of the Federal Food, Drug, and Cosmetic Act (October 2019).
`https://www.fda.gov/RegulatoryInformation/Guidances/default.htm.
`U.S. Food and Drug Administration
`Silver Spring, MD 20993
`www.fda.gov
`
`Reference ID: 4664690
`
`

`

`NDA 214120
`Page 4
`
`
`
`PROMOTIONAL MATERIALS
`
`You may request advisory comments on proposed introductory advertising and
`promotional labeling. For information about submitting promotional materials, see the
`final guidance for industry Providing Regulatory Submissions in Electronic and Non-
`Electronic Format—Promotional Labeling and Advertising Materials for Human
`Prescription Drugs.4
`
`As required under 21 CFR 314.81(b)(3)(i), you must submit final promotional materials,
`and the Prescribing Information, at the time of initial dissemination or publication,
`accompanied by a Form FDA 2253. Form FDA 2253 is available at FDA.gov.5
`Information and Instructions for completing the form can be found at 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).
`
`If you have any questions, call Rachel McMullen, Senior Regulatory Project Manager, at
`(240) 402-4574.
`
`
`
`Sincerely,
`
`{See appended electronic signature page}
`
`R. Angelo de Claro, MD
`Acting Division Director
`Division of Hematologic Malignancies I
`Office of Oncologic Diseases
`Center for Drug Evaluation and Research
`
`
`
`
`
`
`ENCLOSURES:
`• Content of Labeling
`o Prescribing Information
`o Patient Package Insert
`
`
`
`4 For the most recent version of a guidance, check the FDA guidance web page at
`https://www.fda.gov/media/128163/download.
`5 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf
`6 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf
`U.S. Food and Drug Administration
`Silver Spring, MD 20993
`www.fda.gov
`
`Reference ID: 4664690
`
`

`

`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/
`------------------------------------------------------------
`
`ROMEO A DE CLARO
`09/01/2020 10:42:42 AM
`
`Reference ID: 4664690
`
`
`
`