Assyro AI
US FDA•United StatesAL•Approval Letter

Approval Letter Other (Nov 13, 2025)

Issued November 13, 2025

Issued

November 13, 2025

Application

Other

Review center

Other

Stage

Final Decision

Letter type

Approval Letter

Response due November 13, 2026Product may be marketed.

Summary

This document is a deficiency letter from the FDA regarding New Drug Application (NDA) 216190, outlining specific deficiencies related to prescribing information, carton and container labeling, proprietary name, and a comprehensive safety update. It also details the process for resubmission or other actions, including potential withdrawal if no action is taken within one year.

Key points

  • 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).
  • Resubmit the proposed proprietary name, Ontralfy, after addressing all application deficiencies.
  • Include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b) when responding to deficiencies.
  • The safety update must include data from all nonclinical and clinical studies/trials of the drug/product under consideration regardless of indication, dosage form, or dose level.
  • Describe in detail any significant changes or findings in the safety profile within the safety update.
  • Incorporate new safety data when assembling sections describing discontinuations due to adverse events, serious adverse events, and common adverse events.
  • 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/supplemental application data.

Cited reasons

  • Proprietary Name Resubmission Required
  • Incomplete Safety Update per 21 CFR 314.50(d)(5)(vi)(b)
  • Inadequate Adverse Event Data Presentation for Other Indications
  • Missing Case Report Forms and Narrative Summaries for Deaths/SAEs
  • Incomplete Clinical Exposure Information
  • Missing Summary of Worldwide Safety Experience
  • Missing English Translations of Foreign Labeling
  • The application received a Complete Response Letter primarily due to significant deficiencies in the safety update, including incomplete clinical data presentation, missing case report forms and narrative summaries for adverse events, inadequate exposure information, and lack of a worldwide safety summary. Additionally, English translations of foreign labeling and resubmission of the proprietary name are required.

Recommended actions

  • 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).
  • Resubmit the proposed proprietary name, Ontralfy, after addressing all application deficiencies.
  • Include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b) when responding to deficiencies.
  • The safety update must include data from all nonclinical and clinical studies/trials of the drug/product under consideration regardless of indication, dosage form, or dose level.
  • Describe in detail any significant changes or findings in the safety profile within the safety update.
  • Incorporate new safety data when assembling sections describing discontinuations due to adverse events, serious adverse events, and common adverse events.
  • 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/supplemental application data.

Deficiency summary

The application received a Complete Response Letter primarily due to significant deficiencies in the safety update, including incomplete clinical data presentation, missing case report forms and narrative summaries for adverse events, inadequate exposure information, and lack of a worldwide safety summary. Additionally, English translations of foreign labeling and resubmission of the proprietary name are required.

Findings

Proprietary Name Resubmission Required

Severity: minor

The proposed proprietary name, Ontralfy, was found conditionally acceptable but requires resubmission when all application deficiencies are addressed.

Recommended response: Resubmit the proposed proprietary name along with the complete response to all other deficiencies.

Incomplete Safety Update per 21 CFR 314.50(d)(5)(vi)(b)

Severity: major

A comprehensive safety update is required, including data from all nonclinical and clinical studies/trials regardless of indication, dosage form, or dose level, as described in 21 CFR 314.50(d)(5)(vi)(b).

Recommended response: Provide a detailed safety update covering all nonclinical and clinical data as per regulatory requirements.

Cited: 21 CFR 314.50(d)(5)(vi)(b)

Inadequate Adverse Event Data Presentation for Other Indications

Severity: major

Separate tables for the frequencies of adverse events occurring in clinical trials for indications other than the proposed indication must be provided.

Recommended response: Generate and submit separate adverse event frequency tables for all non-proposed indications.

Missing Case Report Forms and Narrative Summaries for Deaths/SAEs

Severity: major

Case report forms and narrative summaries are required for each subject who died during a clinical trial or who did not complete a trial due to an adverse event. Narrative summaries for all serious adverse events are also required.

Recommended response: Compile and submit all requested case report forms and narrative summaries for deaths, trial discontinuations due to AEs, and all serious adverse events.

Incomplete Clinical Exposure Information

Severity: major

Updated exposure information for the clinical studies/trials (e.g., number of subjects, person time) must be provided.

Recommended response: Provide updated and complete clinical exposure data for all relevant studies.

Missing Summary of Worldwide Safety Experience

Severity: major

A summary of worldwide experience on the safety of this drug/product, including an updated estimate of use for drug/product marketed in other countries, is required.

Recommended response: Prepare and submit a comprehensive summary of worldwide safety data and product usage.

Missing English Translations of Foreign Labeling

Severity: major

English translations of current approved foreign labeling not previously submitted must be provided.

Recommended response: Submit English translations for all approved foreign labeling that has not yet been provided.

Regulatory context

Submission stage
final decision
Regulatory pathway
NDA

Impact

Impact score
0.75
Estimated delay
545 days
Estimated rework cost
$0
Subsequent action
resubmission

Strategic insights

The application is not approvable due to substantial deficiencies in the safety data package, requiring a comprehensive update and re-analysis of clinical safety information, along with administrative and labeling corrections.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 25%

Document viewer

Read the FDA letter and send context to the co-pilot at any time.

Loading document viewer…