Complete Response Letter NDA 505b1 218353 (Apr 25, 2025)

Summary

This FDA letter communicates deficiencies in New Drug Application (NDA) 218353 for floretyrosine F 18, requiring the applicant to address issues related to efficacy evidence, dose optimization, prescribing information, carton and container labeling, and a comprehensive safety update. It outlines specific requirements for the safety update data presentation and sets a one-year deadline for resubmission or other actions.

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.
• Review labeling review resources on the Prescription Drug Labeling Resources and Pregnancy and Lactation Labeling Final Rule websites, including regulations, guidance documents, and the Selected Requirements for Prescribing Information (SRPI) checklist.
• 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 within the safety update.
• Present new safety data from studies/clinical trials for the proposed indication using the same format as in the original submission.
• Present tabulations of the 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.

Cited reasons

• Insufficient Evidence of Efficacy
• Incomplete Safety Update and Data Presentation
• Missing English Translations of Foreign Labeling
• The application for floretyrosine F 18 received a Complete Response Letter primarily due to insufficient evidence of efficacy, requiring a new adequate and well-controlled study. Additionally, a comprehensive safety update, including detailed data presentations and worldwide experience, is required. Minor deficiencies include the submission of English translations for foreign labeling.

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.
• Review labeling review resources on the Prescription Drug Labeling Resources and Pregnancy and Lactation Labeling Final Rule websites, including regulations, guidance documents, and the Selected Requirements for Prescribing Information (SRPI) checklist.
• 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 within the safety update.
• Present new safety data from studies/clinical trials for the proposed indication using the same format as in the original submission.
• Present tabulations of the 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.

Deficiency summary

The application for floretyrosine F 18 received a Complete Response Letter primarily due to insufficient evidence of efficacy, requiring a new adequate and well-controlled study. Additionally, a comprehensive safety update, including detailed data presentations and worldwide experience, is required. Minor deficiencies include the submission of English translations for foreign labeling.

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 is the lack of robust clinical efficacy data, necessitating a new study, coupled with significant deficiencies in the completeness and presentation of safety information. There are also minor administrative issues related to foreign labeling.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 5%