FDA Grants Priority Review to Baloxavir Marboxil for Influenza

The US Food and Drug Administration (FDA) announced the acceptance of Genentech’s new drug application, granting priority review for baloxavir marboxil as a single-dose, oral treatment for acute, uncomplicated influenza in patients 12 years of age and older.

The new drug application is backed by results from the phase 3 CAPSTONE-1 study of a single dose of baloxavir marboxil compared with placebo or oseltamivir 75 mg, twice daily for 5 days, in an otherwise healthy patient population with the flu. Results from a placebo-controlled phase 2 study are also included as supporting data.

“The severity of the recent flu season underscores the need for new options beyond currently available treatments, and if approved, baloxavir marboxil would be the first flu medicine with a novel proposed mechanism of action in nearly 20 years,” Sandra Horning, MD, chief medical officer, head of global product development, Roche Holding AG, said in a statement. “Baloxavir marboxil has been shown in clinical trials to decrease the duration of symptoms with 1 dose, and demonstrated a significant reduction in viral shedding in just 1 day. We look forward to working with the FDA during the review process.”

CAPSTONE-1 evaluated the efficacy and safety of baloxavir marboxil in 1436 people in the US and Japan.

Primary endpoint was time to alleviation of symptoms, while important secondary endpoints were time to resolution of fever, time to cessation of viral shedding and the proportion of participants positive for influenza virus titer, or virus levels in the body, by time point.

Data showed that baloxavir marboxil met its primary and secondary endpoints versus placebo, significantly reducing the duration of flu symptoms by more than 1 day (median time 53.7 hours versus 80.2 hours; P < 0.0001); significantly reducing the duration of fever by nearly 1 day (median time 24.5 hours versus 42 hours; P < 0.0001); significantly reducing the length of time viruses continued to be released from the body (median time of viral shedding; 24 hours versus 96 hours; P < 0.0001); and significantly reducing the levels of virus in the nose and throat from 24 hours through 120 hours.

Researchers found similar results to occur in the baloxavir marboxil cohort and oseltamivir cohort in relation to duration of symptoms and fever reduction, however, significant differences were observed in time to cessation of viral shedding, favoring baloxavir marboxil. There was no significant reduction in duration of symptoms (median time 53.5 hours versus 53.8 hours; P = 0.9225); no significant reduction in time to resolution of fever (median time 24.4 hours versus 24 hours; P = 0.9225); a significantly reduced time of viral shedding (24 hours versus 72 hours; P < 0.0001); and significantly reduced levels of virus in the nose and throat at 24 and 72 hours.

The investigational treatment was well-tolerated and had a lower overall incidence of adverse effects (20.7%) reported versus placebo (24.6%) or oseltamivir (24.8%). Most common adverse effects reported were diarrhea (3%), bronchitis (2.6%), nausea (1.3%) and sinusitis (1.1%), which occurred at a lower frequency than placebo.

Baloxavir marboxil, a first-in-class, single-dose investigational oral medicine with a novel proposed mechanism of action, is designed to target the flu virus including oseltamivir-resistant strains and avian strains (H7N9, H5N1) by inhibiting the cap-dependent endonuclease protein within the flu virus.

The FDA is expected to make a decision by Dec. 24, 2018 on approval.