sanofi-aventis U.S. LLCFexinidazole tablets, 600 mg

NDA 214429 COMPLETE RESPONSE

sanofi-aventis U.S. LLC

A SANOFI COMPANY

Attention: Michael Macalush, MS

Director, North America and Global Regulatory Affairs 55 Corporate Drive

Mail Code: 55C-205A

Bridgewater, NU 08807-5925

Dear Mr. Macalush:

Please refer to your new drug application (NDA) dated March 12, 2020, received March 12, 2020, and your amendments, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act for Fexinidazole tablets, 600 mg.

We have completed our review of this application, as amended, and have determined that we cannot approve this application in its present form. We have described our reason for this action below and, where possible, our recommendations to address the issue.

On November 9, 2020, you notified us that you will not be able to submit revised labeling during this review cycle. Therefore, an agreement could not be reached regarding product labeling.

To address this deficiency, submit draft labeling that addresses our proposed revisions to the labeling communicated to you via email on November 4, 2020.

PRESCRIBING INFORMATION

Prior to resubmitting the labeling, use the SRPI checklist to correct any formatting errors to ensure conformance with the format items in regulations and guidances. In addition, submit updated content of labeling [21 CFR 314.50(I)(1)(i)] in structured product labeling (SPL) format as described at FDA.gov.'

To facilitate review of your submission, provide a highlighted or marked-up copy that shows all changes, as well as a clean Word version. The marked-up copy should include annotations that support any proposed changes.

1 http://www.fda.gov/Forlndustry/DataStandards/StructuredProductLabeling/default.htm

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Your proposed Prescribing Information (PI) must conform to the content and format regulations found at 21 CFR 201.56(a) and (d) and 201.57. As you develop your proposed PI, we encourage you to review the labeling review resources on the PLR Requirements for Prescribing Information? and Pregnancy and Lactation Labeling Final Rule? websites, which include:

e The Final Rule (Physician Labeling Rule) on the content and format of the PI for human drug and biological products

e The Final Rule (Pregnancy and Lactation Labeling Rule) on the content and format of information in the PI on pregnancy, lactation, and females and males of reproductive potential

e Regulations and related guidance documents e Asample tool illustrating the format for Highlights and Contents, and

e The Selected Requirements for Prescribing Information (SRPI) - a checklist of important format items from labeling regulations and guidances.

e FDA's established pharmacologic class (EPC) text phrases for inclusion in the Highlights Indications and Usage heading.

CARTON AND CONTAINER LABELING

Submit carton and container labeling identical to the carton (wallet) labeling submitted August 18, 2020, and the container (blistercards) labeling submitted September 2, 2020.

SAFETY UPDATE

When you respond to the above deficiency, include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b). The safety update should include data from all nonclinical and clinical studies/trials of the drug under consideration regardless of indication, dosage form, or dose level.

(1) Describe in detail any significant changes or findings in the safety profile.

(2) When assembling the sections describing discontinuations due to adverse events, serious adverse events, and common adverse events, incorporate new

safety data as follows:

http://www.fda.gov/Drugs/GuidanceComplianceReqgulatory|Information/LawsActsandRules/ucm08415 9.htm

3 http://www. fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/Labeling/ucm09330 7.htm U.S. Food and Drug Administration

Silver Spring, MD 20993

www.fda.gov

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NDA 214429 Page 3

e Present new safety data from the studies/clinical trials for the proposed indication using the same format as in the original submission.

e Present tabulations of the new safety data combined with the original application data.

e Include tables that compare frequencies of adverse events in the original application with the retabulated frequencies described in the bullet above.

e For indications other than the proposed indication, provide separate tables for the frequencies of adverse events occurring in clinical trials.

(3) Present a retabulation of the reasons for premature trial discontinuation by incorporating the drop-outs from the newly completed trials. Describe any new trends or patterns identified.

(4) Provide case report forms and narrative summaries for each patient who died during a Clinical trial or who did not complete a trial because of an adverse event. In addition, provide narrative summaries for serious adverse events.

(5) Describe any information that suggests a substantial change in the incidence of common, but less serious, adverse events between the new data and the original application data.

(6) Provide updated exposure information for the clinical studies/trials (e.g., number of subjects, person time).

(7) Provide a summary of worldwide experience on the safety of this drug. Include an updated estimate of use for drug marketed in other countries.

(8) Provide English translations of current approved foreign labeling not previously submitted.

OTHER

Within one year after the date of this letter, you are required to resubmit or take other actions available under 21 CFR 314.110. If you do not take one of these actions, we may consider your lack of response a request to withdraw the application under

21 CFR 314. You may also request an extension of time in which to resubmit the application.

A resubmission must fully address the deficiency listed in this letter and should be clearly marked with "RESUBMISSION" in large font, bolded type at the beginning of the cover letter of the submission. The cover letter should clearly state that you consider this resubmission a complete response to the deficiencies outlined in this letter. A partial

U.S. Food and Drug Administration Silver Spring, MD 20993 www.fda.gov

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NDA 214429 Page 4

response to this letter will not be processed as a resubmission and will not start a new review cycle.

You may request a meeting or teleconference with us to discuss what steps you need to take before the application may be approved. If you wish to have such a meeting, submit your meeting request as described in the draft guidance for industry Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products.

The drug product may not be legally marketed until you have been notified in writing that this application is approved.

If you have any questions, call Alison Rodgers, Regulatory Project Manager, at 301-796-0797.

Sincerely,

{See appended electronic signature page} John Farley, MD, MPH

Director

Office of Infectious Diseases Center for Drug Evaluation and Research

U.S. Food and Drug Administration Silver Spring, MD 20993 www.fda.gov

Reference ID: 4700697

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.

JOHN J FARLEY 11/12/2020 02:45:30 PM

Reference ID: 4700697