Complete Response Letter NDA 505b1 216442 (Apr 2, 2025)

Summary

The FDA has identified deficiencies in NDA 216442, primarily concerning the robustness of Study 030's primary efficacy endpoint analysis and the statistical methodology used. The agency requires the applicant to conduct at least one additional adequate and well-controlled study to demonstrate positive treatment effects for ocular symptoms of dry eye, without making unapproved protocol or statistical analysis plan changes. Further comments on prescribing information, carton/container labeling, and proprietary name are reserved until the application is otherwise adequate. A safety update is also required upon resubmission, and the applicant must take action within one year to resubmit or risk withdrawal of the application.

Key points

• Conduct at least one additional adequate and well-controlled study to demonstrate a positive effect on the treatment of ocular symptoms of dry eye.
• Do not make changes to the protocol or statistical analysis plan after the first subject is enrolled in the study without expressed agreement by the FDA.
• Review labeling review resources on the Prescription Drug Labeling Resources and Pregnancy and Lactation Labeling Final Rule websites.
• Include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b) when responding to deficiencies.
• Resubmit the proposed proprietary name when all application deficiencies have been identified in this letter are addressed.
• Resubmit the application or take other actions available under 21 CFR 314.110 within one year after the date of this letter.
• Ensure a resubmission fully addresses the deficiencies listed in this letter and is clearly marked with 'RESUBMISSION' in large font, bolded type at the beginning of the cover letter.
• Clearly state in the cover letter that the resubmission is considered a complete response to the deficiencies outlined in this letter.

Cited reasons

• Inadequate Clinical Efficacy Data and Statistical Analysis for Study 030
• Prescribing Information Reserved
• Carton and Container Labeling Reserved
• Proprietary Name Resubmission Required
• Comprehensive Safety Update Required for Resubmission
• The application received a Complete Response Letter primarily due to inadequate clinical efficacy data and statistical analysis issues in Study 030, necessitating an additional pivotal clinical study. Secondary issues include reserved comments on labeling and a requirement to resubmit the proprietary name and provide a safety update upon resubmission.

Recommended actions

• Conduct at least one additional adequate and well-controlled study to demonstrate a positive effect on the treatment of ocular symptoms of dry eye.
• Do not make changes to the protocol or statistical analysis plan after the first subject is enrolled in the study without expressed agreement by the FDA.
• Review labeling review resources on the Prescription Drug Labeling Resources and Pregnancy and Lactation Labeling Final Rule websites.
• Include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b) when responding to deficiencies.
• Resubmit the proposed proprietary name when all application deficiencies have been identified in this letter are addressed.
• Resubmit the application or take other actions available under 21 CFR 314.110 within one year after the date of this letter.
• Ensure a resubmission fully addresses the deficiencies listed in this letter and is clearly marked with 'RESUBMISSION' in large font, bolded type at the beginning of the cover letter.
• Clearly state in the cover letter that the resubmission is considered a complete response to the deficiencies outlined in this letter.

Deficiency summary

The application received a Complete Response Letter primarily due to inadequate clinical efficacy data and statistical analysis issues in Study 030, necessitating an additional pivotal clinical study. Secondary issues include reserved comments on labeling and a requirement to resubmit the proprietary name and provide a safety update upon resubmission.

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 inadequacy of clinical efficacy data, specifically statistical analysis issues in Study 030, necessitating an additional pivotal study. Labeling and proprietary name issues are secondary and contingent on clinical resolution.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 5%