Complete Response Letter NDA 505b1 216586 (Mar 20, 2025)

Summary

The FDA issued a Complete Response Letter (CRL) for NDA 216586 for rivoceranib tablets, indicating that the application cannot be approved in its present form due to outstanding issues, primarily concerning the co-dependent approval of SHR-1210 and labeling adequacy.

Key points

• The applicant must await regulatory approval of SHR-1210 before rivoceranib can be approved, as its safety and effectiveness have only been established in combination with SHR-1210.
• If labeling is revised, the applicant must use the Selected Requirements for Prescribing Information (SRPI) checklist to ensure conformity with format items in regulations and guidances.
• Any revised labeling must include updated content of labeling [21 CFR 314.50(l)(1)(i)] in structured product labeling (SPL) format.
• The applicant must resubmit the proposed proprietary name when responding to the identified application deficiencies.
• Within one year from the date of the letter, the applicant is required to resubmit the application or take other actions available under 21 CFR 314.110.
• A resubmission must fully address all deficiencies listed in this letter and be clearly marked with 'RESUBMISSION' in large, bolded type at the beginning of the cover letter.
• The cover letter for a resubmission must clearly state that the applicant considers it a complete response to the outlined deficiencies.
• The product may not be legally marketed until the applicant has been notified in writing that this application is approved.

Cited reasons

• Safety and Effectiveness Dependent on Unapproved Co-administered Drug
• Reserved Comment on Prescribing Information
• Reserved Comment on Carton and Container Labeling
• Proprietary Name Resubmission Required
• The application for rivoceranib tablets cannot be approved in its current form primarily because its safety and effectiveness have only been established in combination with SHR-1210, which has not yet received regulatory approval. Additionally, comments on proposed labeling (prescribing information, carton, and container) are reserved until the application is otherwise adequate, and the proprietary name requires resubmission with the response to deficiencies.

Recommended actions

• The applicant must await regulatory approval of SHR-1210 before rivoceranib can be approved, as its safety and effectiveness have only been established in combination with SHR-1210.
• If labeling is revised, the applicant must use the Selected Requirements for Prescribing Information (SRPI) checklist to ensure conformity with format items in regulations and guidances.
• Any revised labeling must include updated content of labeling [21 CFR 314.50(l)(1)(i)] in structured product labeling (SPL) format.
• The applicant must resubmit the proposed proprietary name when responding to the identified application deficiencies.
• Within one year from the date of the letter, the applicant is required to resubmit the application or take other actions available under 21 CFR 314.110.
• A resubmission must fully address all deficiencies listed in this letter and be clearly marked with 'RESUBMISSION' in large, bolded type at the beginning of the cover letter.
• The cover letter for a resubmission must clearly state that the applicant considers it a complete response to the outlined deficiencies.
• The product may not be legally marketed until the applicant has been notified in writing that this application is approved.

Deficiency summary

The application for rivoceranib tablets cannot be approved in its current form primarily because its safety and effectiveness have only been established in combination with SHR-1210, which has not yet received regulatory approval. Additionally, comments on proposed labeling (prescribing information, carton, and container) are reserved until the application is otherwise adequate, and the proprietary name requires resubmission with the response to deficiencies.

Findings

Regulatory context

Submission stage

final decision

Regulatory pathway

NDA

Impact

Impact score

0.95

Estimated delay

365 days

Estimated rework cost

$0

Subsequent action

resubmission

Strategic insights

The application's approval is contingent on the regulatory status of a co-administered drug, with all labeling and proprietary name issues deferred until this fundamental clinical and regulatory dependency is resolved.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 5%