Eli Lilly and CompanyLY3074828 injection for moderately to severely active ulcerative colitis

BLA 761279 COMPLETE RESPONSE

Eli Lilly and Company

Attention: Conrad J. Wong, Ph.D.

Senior Director

Global Regulatory Affairs — North America Lilly Corporate Center, Drop Code 2543 Indianapolis, IN 46285

Dear Dr. Wong:

Please refer to your biologics license application (BLA) dated and received March 30, 2022, submitted under section 351(a) of the Public Health Service Act for LY3074828 injection for moderately to severely active ulcerative colitis.

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 reasons for this action below and, where possible, our recommendations to address these issues.

FACILITY INSPECTIONS

Following pre-license inspection of the ELI LILLY AND COMPANY, Indianapolis, Indiana (FEI 1819470), manufacturing facility listed in this application, FDA conveyed deficiencies to the representative of the facility. Satisfactory resolution of these deficiencies is required before this application may be approved.

PRESCRIBING INFORMATION

Submit draft labeling that is responsive to your electronic communication dated March 15, 2023, for the Prescribing Information and Medication Guide and March 2, 2023, for the Instructions for Use.

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 601.14(b)] in structured product labeling (SPL) format as described at FDA.gov.'

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

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BLA 761279 Page 2

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.

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 Prescription Drug Labeling Resources? and Pregnancy and Lactation Labeling Final Rule? websites, which include:

e The Final Rule (Physician Labeling Rule) on the content and format of the Pl 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.

e Additional resources for the PI, patient labeling, and carton/container labeling. CARTON AND CONTAINER LABELING

Submit draft carton and container and device labeling that is responsive to our electronic communications dated September 15, 2022, and January 31, 2023.

Add the following bolded statement or appropriate alternative to the carton and container labeling per 21 CFR 208.24(d): a

PROPRIETARY NAME

Please refer to correspondence dated November 2, 2022, which addresses the proposed proprietary name, Omvoh. This name was found acceptable pending approval

2 https://www.fda. gov/drugs/laws-acts-and-rules/prescription-drug-labeling-resources

final-rule

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

Reference ID: 5150402

BLA 761279 Page 3

of the application in the current review cycle. Please resubmit the proposed proprietary name when you respond to the application deficiencies.

SAFETY UPDATE

When you respond to the above deficiencies, 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 product under consideration regardless of indication, dosage form, or dose level.

(1) (2)

(3)

(4)

(5

(6)

(7)

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

When assembling the sections describing discontinuations due to adverse events, serious adverse events, and common adverse events, incorporate new safety data as follows:

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.

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

Provide case report forms and narrative summaries for each subject 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.

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.

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

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

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

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

ADDITIONAL COMMENTS

We have the following comments/recommendations that are not approvability issues:

MICROBIOLOGY

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

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PRODUCT QUALITY

(5) Per 21 CFR 601.20(b)(1), issuance of a biologics license requires that “the product intended for introduction into interstate commerce is available for examination”. To be consistent with 21 CFR 601.20(b)(1), the BLA should contain data for at least one drug product lot suitable for commercial release. a

Clarify whether a drug product lot(s) manufactured using validated drug substance and drug product processes will be available for launch, should your BLA be approved, and indicate the timeline for manufacture.

OTHER

Within one year after the date of this letter, you are required to resubmit or take other actions available under 21 CFR 601.3(b)). 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 601.3(c). You may also request an extension of time in which to resubmit the application.

A resubmission must fully address all the deficiencies 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 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.

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

Reference ID: 5150402

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If you have any questions, contact Kelly Richards, Senior Regulatory Health Project Manager, at (240) 402-4276 or email at kelly.richards@fda.hhs.gov

Sincerely, {See appended electronic signature page}

Julie Beitz, MD

Director

Office of Immunology and Inflammation Office of New Drugs

Center for Drug Evaluation and Research

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

Reference ID: 5150402

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.

JULIE G BEITZ 03/30/2023 10:57:26 AM

Reference ID: 5150402