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Center for Drug Evaluation and Research CENTER FOR DRUG EVALUATION AND RESEARCH Approval Package for: APPLICATION NUMBER: 022433Orig1s028 Trade Name: Brilinta tablets Generic or Proper ticagrelor Name: Sponsor: AstraZeneca Pharmaceuticals LP Approval Date: May 28, 2020 Indication: BRILINTA is indicated to reduce the risk of a first MI or stroke in patients with coronary artery disease (CAD) at high risk for such events. While use is not limited to this setting, the efficacy of BRILINTA was established in a population with type 2 diabetes mellitus (T2DM). CENTER FOR DRUG EVALUATION AND RESEARCH 022433Orig1s028 CONTENTS Reviews / Information Included in this NDA Review. Approval Letter X Other Action Letters Labeling X REMS Summary Review X Officer/Employee List Office Director Memo Cross Discipline Team Leader Review Clinical Review(s) X Product Quality Review(s) Non-Clinical Review(s) Statistical Review(s) Clinical Microbiology / Virology Review(s) Clinical Pharmacology Review(s) Other Reviews X Risk Assessment and Risk Mitigation Review(s) Proprietary Name Review(s) Administrative/Correspondence Document(s) CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 022433Orig1s028 APPROVAL LETTER NDA 22433/S-028 SUPPLEMENT APPROVAL AstraZeneca Pharmaceuticals LP Attn: Jeffy G. John, MBA Director, Regulatory Affairs One MedImmune Way Gaithersburg, MD 20878 Dear Mr. John: Please refer to your supplemental new drug application (sNDA) dated 30 July 2019, received 30 July 2019, and your amendments, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for Brilinta (ticagrelor) tablets. This Prior Approval supplemental new drug application provides for the following new indication: BRILINTA is indicated to reduce the risk of a first MI or stroke in patients with coronary artery disease (CAD) at high risk for such events. While use is not limited to this setting, the efficacy of BRILINTA was established in a population with type 2 diabetes mellitus (T2DM). Additional revisions related to this new indication have been made throughout the prescribing information. 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 Medication Guide), 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 labeling. 1 http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm Reference ID: 4615549 NDA 22433/S-028 Page 2 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 from publicly available labeling repositories. 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). 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. We are waiving the pediatric study requirement for this application because necessary studies are impossible or highly impracticable. 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.3 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 FDA.gov.4 Information and Instructions for completing the form can be found at FDA.gov.5 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. 3 For the most recent version of a guidance, check the FDA guidance web page at https://www.fda.gov/media/128163/download. 4 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf 5 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: 4615549 NDA 22433/S-028 Page 3 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, please call Bridget Kane, Regulatory Project Manager, at (240) 402-2170. Sincerely, {See appended electronic signature page} Norman Stockbridge, MD, PhD Director Division of Cardiology and Nephrology Office of Cardiology, Hematology, Endocrinology, and Nephrology Center for Drug Evaluation and Research ENCLOSURES: • Content of Labeling o Prescribing Information o Medication Guide U.S. Food and Drug Administration Silver Spring, MD 20993 www.fda.gov Reference ID: 4615549 ( 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/ ------------------------------------------------------------ NORMAN L STOCKBRIDGE 05/28/2020 12:46:58 PM Reference ID: 4615549 CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 022433Orig1s028 LABELING HIGHLIGHTS OF PRESCRIBING INFORMATION ---------------------- DOSAGE AND ADMINISTRATION ---------------------- These highlights do not include all the information needed to use • ACS or History of MI BRILINTA safely and effectively. See full prescribing information for o In the management of ACS, initiate treatment with 180 mg oral BRILINTA. loading dose. Then administer 90 mg twice daily during the first year. After one year, administer 60 mg twice daily. (2.1) BRILINTA® (ticagrelor) tablets, for oral use • Patients with CAD and No Prior Stroke or MI Initial U.S. Approval: 2011 o Administer 60 mg twice daily. (2.2) WARNING: (A) BLEEDING RISK, and (B) ASPIRIN DOSE AND Use BRILINTA with a daily maintenance dose of aspirin of 75-100 mg. (2.3, BRILINTA EFFECTIVENESS 5.2) See full prescribing information for complete boxed warning. --------------------- DOSAGE FORMS AND STRENGTHS -------------------- BLEEDING RISK • 60 mg and 90 mg tablets (3) • BRILINTA, like other antiplatelet agents, can cause significant, ------------------------------ CONTRAINDICATIONS ----------------------------- sometimes fatal bleeding. (5.1, 6.1) • History of intracranial hemorrhage. (4.1) • Do not use BRILINTA in patients with active pathological • Active pathological bleeding. (4.2) bleeding or a history of intracranial hemorrhage. (4.1, 4.2) • Hypersensitivity to ticagrelor or any component of the product. (4.3) • Do not start BRILINTA in patients undergoing urgent coronary artery bypass graft surgery (CABG). (5.1, 6.1) ----------------------- WARNINGS AND PRECAUTIONS ---------------------- • If possible, manage bleeding without discontinuing BRILINTA. • Dyspnea was reported more frequently with BRILINTA than with control Stopping BRILINTA increases the risk of subsequent agents in clinical trials. Dyspnea from BRILINTA is self-limiting. (5.3) cardiovascular events. (5.4) • Severe Hepatic Impairment: Likely increase in exposure to ticagrelor. (5.6) ASPIRIN DOSE AND BRILINTA EFFECTIVENESS • Laboratory Test Interference: False negative platelet functional test results • Maintenance doses of aspirin above 100 mg daily reduce the have been reported for Heparin Induced Thrombocytopenia (HIT). effectiveness of BRILINTA and should be avoided. (2.3, 5.2, 14.1) BRILINTA is not expected to impact PF4 antibody testing for HIT. (5.7) -------------------------- RECENT MAJOR CHANGES -------------------------- ------------------------------ ADVERSE REACTIONS ----------------------------- Indications and Usage (1.2) 05/2020 Most common adverse reactions (>5%) are bleeding and dyspnea. (5.1, 5.3, Dosage and Administration (2 2) 05/2020
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