`NDA 022406/S-037
`
`
`
`SUPPLEMENT APPROVAL
`
`
`
`Jannsen Pharmaceuticals, Inc.
`Attention: Huy Truong
`Director, Global Regulatory Affairs
`920 US Highway 202, PO Box 300
`Raritan, NJ 08869-0602
`
`
`Dear Mr. Truong:
`
`Please refer to your supplemental new drug application (sNDA) for NDA 202439 dated
`October 23, 2020, received October 23, 2020, and your amendments, submitted under
`section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for Xarelto
`(rivaroxaban) tablets.
`
`We also refer to your supplemental new drug application (sNDA) for NDA 022406 dated
`June 4, 2021, received June 4, 2021, submitted under Section 505(b) for Xarelto
`(rivaroxaban) tablets to maintain harmonization of Xarelto labeling.
`
`These Prior Approval supplemental new drug applications provide for the following
`indication:
`
`Xarelto, in combination with aspirin, is indicated to reduce the risk of major thrombotic
`vascular events (myocardial infarction, ischemic stroke, acute limb ischemia, and major
`amputation of a vascular etiology) in patients with PAD, including patients who have
`recently undergone a lower extremity revascularization procedure due to symptomatic PAD.
`
`Xarelto had an indication in patients with Coronary Artery Disease or Peripheral Artery
`Disease; these uses are now separately described. This supplement and the VOYAGER-
`PAD study add initiation of Xarelto in patients with a recent revascularization procedure.
`
`Changes were also made to Sections 1 INDICATIONS AND USAGE, 2 DOSING AND
`ADMINISTRATION, 6 ADVERSE REACTIONS, 8 USE IN SPECIFIC POPULATIONS and
`14 CLINICAL STUDIES of the Package Insert. Minor editorial changes were made
`throughout. The Medication Guide was also updated to include information for this new
`indication.
`
`APPROVAL & LABELING
`
`We have completed our review of these applications, as amended. It is approved, effective
`on the date of this letter, for use as recommended in the enclosed agreed-upon labeling.
`
`
`
`Reference ID: 4845827
`
`
`
`NDA 202439/S-035
`NDA 022406/S-037
`Page 2
`
`WAIVER OF ½ PAGE LENGTH REQUIREMENT FOR HIGHLIGHTS
`
`Please note that we have previously granted a waiver of the requirements of 21 CFR
`201.57(d)(8) regarding the length of Highlights of Prescribing Information.
`
`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.
`
`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 (202439/S-035) because
`necessary studies are impossible or highly impracticable because peripheral artery disease
`due to atherosclerosis does not occur in children.
`
`
`
`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.
`
`U.S. Food and Drug Administration
`Silver Spring, MD 20993
`www.fda.gov
`
`Reference ID: 4845827
`
`
`
`NDA 202439/S-035
`NDA 022406/S-037
`Page 3
`
`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
`
`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
`Office of New Drugs
`Center for Drug Evaluation and Research
`
`
`
`
`ENCLOSURES:
`• Content of Labeling
`o Prescribing Information
`o Medication Guide
`
`
`
`
`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: 4845827
`
`
`
`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
`08/23/2021 04:45:45 PM
`
`Reference ID: 4845827
`
`