Complete Response Letter BLA 761366 (Jun 26, 2024)

Summary

This document is a Complete Response Letter (CRL) from the FDA for Biologics License Application (BLA) 761366, detailing deficiencies that must be addressed before the application can be approved. It outlines specific requirements for labeling revisions, proprietary name resubmission, and a comprehensive safety update, along with instructions for resubmission or other actions.

Key points

• Revise labeling using the Selected Requirements for Prescribing Information (SRPI) checklist to ensure conformity with format items in regulations and guidances.
• Include updated content of labeling in structured product labeling (SPL) format as described at FDA.gov.
• Add the bolded statement 'ATTENTION PHARMACIST: Each patient is required to receive the enclosed Medication Guide.' or an appropriate alternative to the carton and container labeling per 21 CFR 208.24(d).
• Resubmit the proposed proprietary name after addressing all application deficiencies.
• Include a safety update with data from all nonclinical and clinical studies/trials of the product, regardless of indication, dosage form, or dose level.
• Describe in detail any significant changes or findings in the safety profile.
• Incorporate new safety data into sections describing discontinuations due to adverse events, serious adverse events, and common adverse events, presenting new data from studies/clinical trials 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

• Proprietary Name Resubmission
• Labeling Format and Content Deficiencies
• Missing English Translations of Foreign Labeling
• Inadequate Comprehensive Safety Update and Data Presentation
• Confirmatory Study Failed Efficacy Endpoint
• The Complete Response Letter identifies significant deficiencies primarily related to the clinical safety data presentation, requiring a comprehensive safety update, detailed narratives for adverse events, and updated exposure information. Labeling issues, including format compliance and a missing Medication Guide statement, also need to be addressed. Critically, the proposed confirmatory study failed to meet its pre-specified efficacy boundary, necessitating further discussion with the agency regarding verification of clinical benefit. The proprietary name, while conditionally acceptable, must be resubmitted with the complete response.

Recommended actions

• Revise labeling using the Selected Requirements for Prescribing Information (SRPI) checklist to ensure conformity with format items in regulations and guidances.
• Include updated content of labeling in structured product labeling (SPL) format as described at FDA.gov.
• Add the bolded statement 'ATTENTION PHARMACIST: Each patient is required to receive the enclosed Medication Guide.' or an appropriate alternative to the carton and container labeling per 21 CFR 208.24(d).
• Resubmit the proposed proprietary name after addressing all application deficiencies.
• Include a safety update with data from all nonclinical and clinical studies/trials of the product, regardless of indication, dosage form, or dose level.
• Describe in detail any significant changes or findings in the safety profile.
• Incorporate new safety data into sections describing discontinuations due to adverse events, serious adverse events, and common adverse events, presenting new data from studies/clinical trials 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 Complete Response Letter identifies significant deficiencies primarily related to the clinical safety data presentation, requiring a comprehensive safety update, detailed narratives for adverse events, and updated exposure information. Labeling issues, including format compliance and a missing Medication Guide statement, also need to be addressed. Critically, the proposed confirmatory study failed to meet its pre-specified efficacy boundary, necessitating further discussion with the agency regarding verification of clinical benefit. The proprietary name, while conditionally acceptable, must be resubmitted with the complete response.

Findings

Regulatory context

Submission stage

final decision

Regulatory pathway

BLA

Impact

Impact score

0.95

Estimated delay

545 days

Estimated rework cost

$0

Subsequent action

resubmission

Strategic insights

The primary themes of the Complete Response are the need for a comprehensive and adequately presented clinical safety update, resolution of various labeling compliance issues, and a critical deficiency regarding the failure of the confirmatory clinical study to meet its primary efficacy endpoint.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 5%