Complete Response Letter NDA 505b1 218592 (Apr 25, 2025)

Summary

This document is a Complete Response Letter (CRL) from the FDA to an applicant for New Drug Application (NDA) 218592, outlining deficiencies that prevent approval and detailing the necessary actions for resubmission.

Key points

• Conduct a second adequate and well-controlled efficacy study or provide other robust confirmatory evidence of efficacy.
• Consider optimization of the administered dose of floretyrosine F 18.
• Address all identified deficiencies in the application.
• Resubmit the proposed proprietary name once all application deficiencies are addressed.
• Include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b) when responding to deficiencies.
• Describe in detail any significant changes or findings in the safety profile in the safety update.
• Incorporate new safety data into sections describing discontinuations due to adverse events, serious adverse events, and common adverse events, presenting new data from studies for the proposed indication in the same format as the original submission.
• Present tabulations of new safety data combined with original application data.

Cited reasons

• Insufficient Efficacy Data
• Proprietary Name Resubmission Required
• Comprehensive Safety Update Required
• Revised Adverse Event Data Presentation
• Retabulation of Premature Discontinuation Reasons
• Submission of Case Report Forms and Narratives
• Analysis of Common Adverse Event Incidence Changes
• Updated Clinical Exposure Information

Recommended actions

• Conduct a second adequate and well-controlled efficacy study or provide other robust confirmatory evidence of efficacy.
• Consider optimization of the administered dose of floretyrosine F 18.
• Address all identified deficiencies in the application.
• Resubmit the proposed proprietary name once all application deficiencies are addressed.
• Include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b) when responding to deficiencies.
• Describe in detail any significant changes or findings in the safety profile in the safety update.
• Incorporate new safety data into sections describing discontinuations due to adverse events, serious adverse events, and common adverse events, presenting new data from studies for the proposed indication in the same format as the original submission.
• Present tabulations of new safety data combined with original application data.

Deficiency summary

The application received a Complete Response Letter primarily due to insufficient efficacy data requiring a new study. Additionally, there are numerous major deficiencies related to the completeness and presentation of safety data, including the need for a comprehensive safety update, detailed adverse event analyses, and submission of critical safety documents. Minor administrative issues regarding proprietary name resubmission and foreign labeling translations were also noted.

Findings

Regulatory context

Submission stage

final decision

Regulatory pathway

NDA

Impact

Impact score

0.95

Estimated delay

730 days

Estimated rework cost

$0

Subsequent action

resubmission

Strategic insights

The primary theme of this Complete Response Letter is the critical lack of sufficient efficacy data, necessitating a new clinical study. This is compounded by extensive deficiencies in the submission and analysis of safety data, requiring comprehensive updates and re-presentations across multiple aspects of the clinical safety profile.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 5%