NeuroDerm, Ltd.carbidopa and levodopa injection

NDA 218317 COMPLETE RESPONSE

NeuroDerm, Ltd.

c/o: The ProPharma Group

Attention: Daniel Solorio

Senior Vice President, Regulatory Program Management 1129 20th Street NW, Suite 600

Washington, DC 20036

Dear Daniel Solorio: Please refer to your new drug application dated

(carbidopa and levodopa) injection.

We acknowledge receipt of a amendment dated |) which constituted a

complete response to our , action letter.

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.

NONCLINICAL

FACILITIES

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

Reference ID: 5681175

NDA 218317 Page 2

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 PAI of the facility. Satisfactory outcomes of both the PAI and the CGMP surveillance inspections will be needed prior to an approval of the application.

PRESCRIBING INFORMATION

We reserve comment on the proposed labeling until the application is otherwise adequate. We encourage you to review the labeling review resources on the Prescription Drug Labeling Resources! and Pregnancy and Lactation Labeling Final Rule? websites, including regulations and related guidance documents and the Selected Requirements for Prescribing Information (SRPI) - a checklist of important format items from labeling regulations and guidances.

CARTON AND CONTAINER LABELING

We reserve comment on the proposed labeling until the application is otherwise adequate.

PROPRIETARY NAME

Please refer to our correspondence dated, om , 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 product under consideration regardless of indication, dosage form, or dose level.

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

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

2 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

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NDA 218317 Page 3

(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 data from the original application and from the

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 he frequencies of adverse events occurring in Clinical trials.

(3) Present a retabulation of the reasons for premature trial discontinuation by incorporating the dropouts 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 data from the original application and the

(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 product. Include an updated estimate of use for this product marketed in other countries.

(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:

Chemistry, Manufacturing, and Controls

(b) (4)

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

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NDA 218317 Page 4

(b) (4)

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 314.65. 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.$

If you have any questions, contact oe (b) (4)

Sincerely,

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

Center for Drug Evaluation and Research

3 https://www.fda.gov/requlatory-information/search-fda-guidance-documents/formal-meetings-between- fda-and-sponsors-or-applicants-pdufa-products

U.S. Food and Drug Administration

Silver Spring, MD 20993

www.fda.gov

Reference ID: 5681175

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)

10/21/2025 05:36:20 PM Signing on behalf of Wb)

Reference ID: 5681175