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 Complete Response letter from the FDA to Genentech, Incorporated, regarding their New Drug Applications (NDAs) and supplemental NDAs (sNDAs) for XOFLUZA (baloxavir marboxil) for the treatment and post-exposure prophylaxis of influenza in pediatric patients. The FDA determined that the applications cannot be approved in their present form due to concerns primarily related to the high frequency of treatment-emergent resistance in pediatric patients and the potential risk of transmission of resistant virus.

Key points

  • Submit data from Trial MV40618 ('A Phase IIIb, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Clinical Efficacy Study of Baloxavir Marboxil for the Reduction of Direct Transmission of Influenza from Otherwise Healthy Patients to Household Contacts') to evaluate the risk of transmission of baloxavir resistant influenza virus.
  • Submit the complete clinical study report and datasets from Study T0835 for full evaluation of resistance.
  • Review labeling review resources and revise labeling if necessary, ensuring conformity with format items in regulations and guidances.
  • Include updated content of labeling in structured product labeling (SPL) format if labeling is revised.
  • Submit a safety update as described at 21 CFR 314.50(d)(5)(vi)(b).
  • 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, combined data, and comparisons with original/supplemental application data.
  • Provide separate tables for the frequencies of adverse events occurring in clinical trials for indications other than the proposed indication.

Cited reasons

  • Insufficient Clinical Data on Transmission Risk of Baloxavir-Resistant Influenza Virus in Pediatric Patients
  • Incomplete Clinical Study Report and Datasets for Study T0835
  • Labeling Review Reserved Pending Clinical Data Resolution
  • Comprehensive Safety Update Required
  • The FDA issued a Complete Response Letter for XOFLUZA (baloxavir marboxil) due to insufficient clinical data regarding the risk of transmission of baloxavir-resistant influenza virus in pediatric patients and incomplete clinical study reports. Additionally, comprehensive safety updates and labeling revisions are required.

Recommended actions

  • Submit data from Trial MV40618 ('A Phase IIIb, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Clinical Efficacy Study of Baloxavir Marboxil for the Reduction of Direct Transmission of Influenza from Otherwise Healthy Patients to Household Contacts') to evaluate the risk of transmission of baloxavir resistant influenza virus.
  • Submit the complete clinical study report and datasets from Study T0835 for full evaluation of resistance.
  • Review labeling review resources and revise labeling if necessary, ensuring conformity with format items in regulations and guidances.
  • Include updated content of labeling in structured product labeling (SPL) format if labeling is revised.
  • Submit a safety update as described at 21 CFR 314.50(d)(5)(vi)(b).
  • 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, combined data, and comparisons with original/supplemental application data.
  • Provide separate tables for the frequencies of adverse events occurring in clinical trials for indications other than the proposed indication.

Deficiency summary

The FDA issued a Complete Response Letter for XOFLUZA (baloxavir marboxil) due to insufficient clinical data regarding the risk of transmission of baloxavir-resistant influenza virus in pediatric patients and incomplete clinical study reports. Additionally, comprehensive safety updates and labeling revisions are required.

Findings

Insufficient Clinical Data on Transmission Risk of Baloxavir-Resistant Influenza Virus in Pediatric Patients

Severity: major

The agency requires submission of data from Trial MV40618 to adequately evaluate the risk of transmission of baloxavir resistant influenza virus from treated index patients, including those less than 12 years of age, given the substantially elevated risk of resistance observed in this population.

Recommended response: Conduct and submit results from Trial MV40618 to assess transmission risk of resistant virus. Provide complete clinical study report and datasets from Study T0835 for full resistance evaluation.

Incomplete Clinical Study Report and Datasets for Study T0835

Severity: major

The complete clinical study report and datasets from Study T0835 are required for full evaluation of resistance, as preliminary data indicated high frequencies of treatment-emergent resistance in pediatric patients.

Recommended response: Submit the complete clinical study report and datasets from Study T0835.

Labeling Review Reserved Pending Clinical Data Resolution

Severity: minor

Comment on the proposed labeling is reserved until the application is otherwise adequate. The applicant is encouraged to review PLR requirements and use the SRPI checklist. Updated content of labeling in SPL format is required upon resubmission.

Recommended response: Review PLR requirements and SRPI checklist. Prepare updated content of labeling in SPL format for resubmission.

Cited: 21 CFR 314.50(l)(1)(i)

Comprehensive Safety Update Required

Severity: major

A comprehensive safety update is required upon response to deficiencies, including data from all nonclinical and clinical studies, detailed changes in safety profile, updated tabulations of adverse events (including comparison with original data), case report forms/narrative summaries for deaths/discontinuations due to AE and serious AEs, updated exposure information, worldwide safety experience, and English translations of foreign labeling.

Recommended response: Provide a complete safety update as per 21 CFR 314.50(d)(5)(vi)(b), incorporating all new nonclinical and clinical data, detailed safety profile changes, updated AE tabulations, case report forms/narratives for critical events, updated exposure, worldwide experience, and translated foreign labeling.

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

Regulatory context

Submission stage
final decision
Regulatory pathway
NDA 505(b)

Impact

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

Strategic insights

The primary theme is the unresolved safety concern regarding the potential for increased transmission of baloxavir-resistant influenza virus in pediatric patients due to high rates of treatment-emergent resistance, necessitating additional clinical data and a comprehensive safety update for approval.

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…