Scholar Rock, Inc.SRK-015 (apitegromab-mstn) injection, for intravenous use

BLA 761463

COMPLETE RESPONSE

Scholar Rock, Inc.

Attention:

Neda Aghajani Memar, PharmD

Senior Director, Global Regulatory Affairs 301 Binney Street, 3ra Floor Cambridge, MA 02142

Dear Dr. Memar:

Please re

(b) (4)

fer to your biologics license application (BLA) oe

for SRK-015 (apitegromab-mstn) injection, for intravenous use.

We have completed our review of this application and have determined that we cannot

approve tl action be!

his application in its present form. We have described our reasons for this low and, where possible, our recommendations to address these issues.

FACILITY INSPECTIONS

Fo

lowing a CGMP inspection of oo

oye) , listed in this application, FDA

conveyed deficiencies to the representative of the facility. The facility should provide satisfactory responses to these deficiencies to the FDA office indicated

on

the FDA 483 prior to your complete response. The facility’s satisfactory

responses are dependent on FDA’s determination that the facility has come into compliance with CGMP and may require re-inspection of the facility. The deficiencies identified during the inspection may not be specific to your application. Therefore, you should coordinate with the facility for timely resolution. Your complete response should include the date(s) of the facility's response(s) to the FDA Form 483. Please refer to Compliance Program CP 7356.002 for guidance on post inspection activities. Following resolution of the CGMP inspection, FDA may need to conduct a PLI of the facility.

PRESCRIBING INFORMATION

(1) Su

OVI ai @)

Reference ID: 5663509

bmit draft labeling that is responsive to our electronic communication dated which may be a resubmission of your draft labeling ided in an electronic response communication also dated

BLA 761463 Page 2

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.'

To facilitate review of your submission, provide a highlighted or marked-up copy hat 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 ‘ormat 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 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.

e Additional resources for the PI, patient labeling, and carton/container labeling.

CARTON AND CONTAINER LABELING

(b) (4)

(2) Submit draft carton and container labeling based on your ,

submission for the container, and your Cay , submission for the carton.

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

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

3 https://www.fda.gov/drugs/labeling-information-drug-products/pregnancy-and-lactation-labeling-drugs-

final-rule

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

Reference ID: 5663509

BLA 761463 Page 3

PROPRIETARY NAME

Please refer to our correspondence dated, oe , which addresses the proposed proprietary name, |. This name was found conditionally acceptable pending approval of the application in the current review cycle. Please resubmit the proposed proprietary name when you respond to all of the application deficiencies that have been identified in this letter.

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 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:

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 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.

(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.

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

Reference ID: 5663509

BLA 761463 Page 4

(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.

POSTMARKETING REQUIREMENTS UNDER 505(0)(3)

Section 505(0)(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 there are no adequate data on the developmental risk associated with use of apitegromab in pregnant women.

Based on the above, FDA has determined that if BLA 761463 is approved, 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 adverse maternal, fetal and infant outcomes resulting from the use of —" (apitegromab) during pregnancy.

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.

Therefore, based on appropriate scientific data, FDA has determined that, if BLA 761463 is approved, you will be required to conduct the following:

Establish a worldwide single-arm pregnancy safety study to collect and analyze information for a minimum of 10 years on pregnancy complications and birth outcomes for exposed pregnancies, including women exposed to apitegromab during pregnancy and a relevant exposure period prior to the start of pregnancy. Provide a complete protocol that includes details regarding how you plan to encourage patients and providers to report pregnancy exposures, measures to ensure complete data capture regarding pregnancy outcomes and any adverse effects in offspring, and plans for comprehensive data analysis.

Any additional specific details of this required postmarketing study, including a timetable and annual reporting requirements, will be described more fully in the approval letter for this application, if it is approved.

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

Reference ID: 5663509

BLA 761463 Page 5

If you complete this study prior to re-submitting your application, you may include the final report and relevant data sets in your Complete Response submission to facilitate review of the information.

ADDITIONAL COMMENTS

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

Product Quality

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.

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

Reference ID: 5663509

BLA 761463 Page 6

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

If you have any questions, contact oe

Sincerely,

{See appended electronic signature page} (b) (4)

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

Reference ID: 5663509

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.

wa) 09/22/2025 05:47:21 PM

Reference ID: 5663509