Janssen Biotech, Inc.amivantamab and hyaluronidase injection

BLA 761433 COMPLETE RESPONSE

Janssen Biotech, Inc.

Attention: Yvonne Wu, Ph.D.

Associate Director, Global Regulatory Affairs 920 U.S. Route 202

Raritan, NJ 08869

Dear Dr. Wu:

Please refer to your biologics license application (BLA) om

or amivantamab and hyaluronidase injection.

We have completed our review of this application 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

1) Following pre-license inspection of the drug product manufacturing facility, oe

, FDA identified deficiencies and communicated them to the representative of the facility. The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA Form 483 prior to resubmitting your application for amivantamab and hyaluronidase injection. Your complete response addressing these deficiencies must include the date of the facility's response to the FDA Form 483. The assessment of the application approvability and the resolution of inspection deficiencies will be evaluated upon receipt of the complete response addressing the deficiencies and may include re- inspection of the facility. Please work with the facility to resolve the deficiencies.

PRESCRIBING INFORMATION

2) In the resubmission for your application, submit draft labeling in response to our electronic communication dated oe

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.

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BLA 761433 Page 2

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 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 (Pl) 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 Dru Lactation Labeling Final Rule? we

g Labeling Resources? and Pregnancy and bsites, which include:

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

for human drug and biological

e The Final Rule (Pregnancy an format of information in the P

males of reproductive potential

products

id Lactation Labeling Rule) on the content and on pregnancy, lactation, and females and

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 P

|, patient labeling, and carton/container labeling.

CARTON AND CONTAINER LABELING

3) In the resubmission for your application, submit draft carton and container

labeling based on our proposed ri

evisions dated

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: 5496143

BLA 761433

Page 3

PROPRIETARY NAME

4) Please refer to correspondence dated oe , which addresses the proposed proprietary name, oe . 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 product under consideration regardless of indication, dosage form, or dose level.

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

B. 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.

C. 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.

D. 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.

E. 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

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BLA 761433 Page 4

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

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

H. Provide English translations of current approved foreign labeling not previously submitted.

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

Product Quali

Clinical Pharmacology

(6) Prior to resubmitting your application for amivantamab and hyaluronidase injection, re-analyze the incidence of anti-amivantamab antibodies from PALOMA using the drug tolerance limit enhanced method which was used in the sample analysis of PALOMA-2 and PALOMA-3.

(7) | Currently, FDA's pharmacokinetic and immunogenicity assessment is contingent upon full evaluation of the data quality and integrity of sample analysis. A final determination on the acceptability will be made once the pending site inspection is complete.

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

Reference ID: 5496143

BLA 761433 Page 5

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 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)

Center for Drug Evaluation and Research

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

Reference ID: 5496143

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.

(b) (4)

12/13/2024 04:19:08 PM

Reference ID: 5496143