Approval Letter Other 215064 (Jan 1, 2024)

Summary

The FDA issued a Complete Response letter for NDA 215064 for Filsuvez (birch triterpenes) gel, indicating that the application cannot be approved in its current form due to insufficient evidence of effectiveness for the proposed indication of treating wounds associated with inherited epidermolysis bullosa (EB). The letter details specific deficiencies in clinical data and outlines requirements for a safety update and other submissions.

Key points

• Submit additional confirmatory evidence of effectiveness of Filsuvez for EB or specific subsets of the EB population.
• Review labeling review resources on the Prescription Drug Labeling Resources and Pregnancy and Lactation Labeling Final Rule websites.
• Resubmit the proposed proprietary name, Filsuvez, when responding to the application deficiencies.
• 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.
• 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 using the same format as 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

• Lack of Substantial Evidence of Effectiveness
• Unsuitable Supportive Clinical Study Designs
• Inadequate Mechanism of Action Data
• Comprehensive Safety Update Required
• Proprietary Name Resubmission Required
• The FDA issued a Complete Response Letter for Filsuvez (birch triterpenes) gel due to a lack of substantial evidence of effectiveness for the proposed indication of treating wounds associated with inherited epidermolysis bullosa (EB). Key issues include insufficient support from secondary endpoints despite meeting the primary endpoint in one study, unsuitability of supportive open-label studies, and inadequate data to support the mechanism of action specific to EB. Additionally, a comprehensive safety update and resubmission of the proprietary name are required upon response.

Recommended actions

• Submit additional confirmatory evidence of effectiveness of Filsuvez for EB or specific subsets of the EB population.
• Review labeling review resources on the Prescription Drug Labeling Resources and Pregnancy and Lactation Labeling Final Rule websites.
• Resubmit the proposed proprietary name, Filsuvez, when responding to the application deficiencies.
• 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.
• 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 using the same format as 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 FDA issued a Complete Response Letter for Filsuvez (birch triterpenes) gel due to a lack of substantial evidence of effectiveness for the proposed indication of treating wounds associated with inherited epidermolysis bullosa (EB). Key issues include insufficient support from secondary endpoints despite meeting the primary endpoint in one study, unsuitability of supportive open-label studies, and inadequate data to support the mechanism of action specific to EB. Additionally, a comprehensive safety update and resubmission of the proprietary name are required upon response.

Findings

Regulatory context

Submission stage

final decision

Regulatory pathway

NDA 505(b)

Impact

Impact score

0.95

Estimated delay

540 days

Estimated rework cost

$0

Subsequent action

resubmission

Strategic insights

The primary theme is the lack of robust clinical evidence to demonstrate substantial effectiveness for the proposed indication, compounded by methodological limitations in supportive studies and insufficient data on the mechanism of action specific to the target disease. This necessitates additional confirmatory clinical data.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 5%