Complete Response Letter NDA 505b1 218762 (Dec 5, 2024)

Summary

This document outlines specific requirements for updating and presenting safety data for NDA 218762, including new clinical trial data, adverse event frequencies, trial discontinuations, and worldwide safety experience. It also sets a deadline for resubmission or other actions.

Key points

• Incorporate new safety data from studies/clinical trials for the proposed indication using the same format as in the original submission.
• Present tabulations of new safety data combined with the original application data.
• Include tables that compare frequencies of adverse events in the original application with the retabulated frequencies.
• 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 drop-outs from newly completed trials.
• Describe any new trends or patterns identified in trial discontinuations.
• 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.
• Provide narrative summaries for serious adverse events.

Cited reasons

• Incomplete Adverse Event Tables for Other Indications
• Missing Case Report Forms and Narrative Summaries for Deaths and Serious Adverse Events
• Incomplete Clinical Exposure Information
• Missing Summary of Worldwide Safety Experience
• Missing English Translations of Foreign Labeling
• The application received a Complete Response Letter due to significant deficiencies primarily related to the presentation and completeness of clinical safety data, including adverse event reporting, case narratives, exposure information, and a lack of a worldwide safety summary. Additionally, English translations of foreign labeling were not provided.

Recommended actions

• Incorporate new safety data from studies/clinical trials for the proposed indication using the same format as in the original submission.
• Present tabulations of new safety data combined with the original application data.
• Include tables that compare frequencies of adverse events in the original application with the retabulated frequencies.
• 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 drop-outs from newly completed trials.
• Describe any new trends or patterns identified in trial discontinuations.
• 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.
• Provide narrative summaries for serious adverse events.

Deficiency summary

The application received a Complete Response Letter due to significant deficiencies primarily related to the presentation and completeness of clinical safety data, including adverse event reporting, case narratives, exposure information, and a lack of a worldwide safety summary. Additionally, English translations of foreign labeling were not provided.

Findings

Regulatory context

Submission stage

final decision

Regulatory pathway

NDA

Impact

Impact score

0.75

Estimated delay

365 days

Estimated rework cost

$0

Subsequent action

resubmission

Strategic insights

The primary theme of the Complete Response Letter is the inadequacy and incompleteness of clinical safety data presentation and reporting, coupled with administrative deficiencies regarding foreign labeling translations. The agency requires a more comprehensive and organized submission of safety information across all indications and global experience.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 25%