FDA approves generic baloxavir marboxil for flu treatment, prophylaxis

The FDA has approved the first generic version of baloxavir marboxil tablets—the single-dose cap-dependent endonuclease inhibitor previously available only as the brand-name agent Xofluza—for the treatment of acute uncomplicated influenza and post-exposure prophylaxis (PEP) in patients 5 years of age and older.¹ The approval, granted to Norwich Pharmaceuticals, Inc, was announced on June 17, 2026, timed to reach the market before the 2026–2027 influenza season.

"Today's approval marks a meaningful milestone for the treatment of influenza," said Iilun Murphy, MD, director of the Office of Generic Drugs in FDA's Center for Drug Evaluation and Research. "Expanding patient access to drugs and improving their ease of use are critical public health imperatives, particularly given that influenza alone accounts for millions of illnesses in the US each year."¹

Regulatory pathway and approved indications

Generic baloxavir marboxil carries the same indications as the reference listed drug. It is indicated for treatment of acute uncomplicated influenza in patients 5 years of age and older who have been symptomatic for no more than 48 hours, including patients who are otherwise healthy and those at high risk of developing influenza-related complications.¹ It is also indicated for PEP of influenza in patients 5 years of age and older following contact with a confirmed case.

The generic application was evaluated under the FDA's Abbreviated New Drug Application (ANDA) pathway, which requires demonstration of bioequivalence to the reference product rather than independent clinical efficacy trials. No new clinical data were generated for the generic approval; the efficacy and safety foundation rests on the trials submitted with the original Xofluza NDA.

Drug class and mechanism

Baloxavir marboxil is a first-in-class cap-dependent endonuclease inhibitor that functions as a prodrug. After oral administration, it is converted to the active metabolite baloxavir acid, which inhibits the polymerase acidic (PA) endonuclease subunit of the influenza RNA-dependent RNA polymerase complex.² This blocks the viral "cap-snatching" mechanism required for synthesis of viral mRNA, halting replication at an earlier step than neuraminidase inhibitors such as oseltamivir and zanamivir. Baloxavir retains activity against neuraminidase inhibitor-resistant strains, and preclinical data have also demonstrated antiviral effects against avian strains including H5N1 and H7N9.²

Xofluza received its initial FDA approval on October 24, 2018, for treatment of acute uncomplicated influenza in patients 12 years of age and older, based on results from the phase 3 CAPSTONE-1 trial (NCT03711305). The indication was subsequently expanded in October 2019 to include high-risk patients and, in November 2020, to include PEP for patients 12 years of age and older. The lower age threshold of 5 years was added later, extending the eligible population to younger children.³

Pivotal clinical evidence

The efficacy of baloxavir marboxil was established primarily in the phase 3 CAPSTONE-1 trial, a randomized, double-blind, placebo- and active comparator-controlled study of 1,436 patients aged 12 to 64 years with acute uncomplicated influenza conducted across sites in the US and Japan during the 2016–2017 season.⁴ Patients were assigned to a single weight-based oral dose of baloxavir marboxil (40 mg or 80 mg), oseltamivir 75 mg twice daily for 5 days, or placebo, within 48 hours of symptom onset.

The primary efficacy end point, time to alleviation of influenza symptoms, was significantly shorter with baloxavir than placebo (median 53.7 hours vs 80.2 hours; P < .001), a difference of 26.5 hours.⁴ Symptom alleviation time was similar between baloxavir and oseltamivir in adult patients. Baloxavir was superior to both oseltamivir and placebo in reducing viral load 1 day after treatment initiation. The safety profile was comparable to placebo, with the most common adverse events including diarrhea, bronchitis, nausea, sinusitis, and headache.

In the high-risk population, the phase 3 CAPSTONE-2 trial (NCT02949011) demonstrated that baloxavir reduced the time to symptom improvement compared with placebo, including in patients with influenza type B virus infection (median 73 hours vs 102 hours; P < .001), supporting the expanded high-risk indication.³

References

1. US Food and Drug Administration. FDA approves first single-dose generic treatment for influenza. News release. FDA. June 17, 2026. Accessed June 18, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-single-dose-generic-treatment-influenza

2. Hayden FG, Sugaya N, Hirotsu N, et al; Baloxavir Marboxil Investigators Group. Baloxavir marboxil for uncomplicated influenza in adults and adolescents. N Engl J Med. 2018;379(10):913-923. doi:10.1056/NEJMoa1716197

3. Centers for Disease Control and Prevention. Influenza antiviral drug baloxavir marboxil. Updated December 19, 2025. Accessed June 18, 2026. https://www.cdc.gov/flu/treatment/baloxavir-marboxil.html

4. Ison MG, Portsmouth S, Yoshida Y, et al. Early treatment with baloxavir marboxil in high-risk adolescent and adult outpatients with uncomplicated influenza (CAPSTONE-2): a randomised, placebo-controlled, phase 3 trial. Lancet Infect Dis. 2020;20(10):1204-1214. doi:10.1016/S1473-3099(20)30004-9