FDA CRL - Genentech, Inc.

The FDA issued a Complete Response Letter (CRL) to Genentech, Incorporated, for its New Drug Applications (NDAs 214410/Original 2, 210854/S-05, 210854/S-09) for XOFLUZA (baloxavir marboxil) oral suspension and tablets. Submitted on January 23, 2020, under section 505(b) of the Federal Food, Drug, and Cosmetic Act, these applications sought approval for influenza treatment and post-exposure prophylaxis in pediatric patients aged 12 months to less than 12 years.

The primary concern highlighted was a significantly elevated risk of treatment-emergent resistance to baloxavir in this pediatric group, observed in approximately 22% to 75% of subjects, particularly with the A/H3N2 virus. This resistance is associated with virus rebound and potential prolonged contagiousness, raising concerns about the transmission of resistant virus to household or community contacts and the potential for widespread baloxavir resistance.

To address these issues, Genentech is required to submit data from Trial MV40618, which investigates influenza transmission reduction, and the complete clinical study report and datasets from Study T0835 for a full evaluation of resistance. Additionally, a comprehensive safety update, detailed in 21 CFR 314.50(d)(5)(vi)(b), including new safety data, adverse event comparisons, and worldwide safety experience, is mandated. Genentech must resubmit the application with all deficiencies addressed within one year.