Baloxavir Marboxil Shows Promise in 2 Phase 3 Studies

In October 2018, the US Food and Drug Administration (FDA) approved baloxavir marboxil (Xofluza) for the treatment of acute, uncomplicated influenza in people 12 years of age and older. The approval marked the first new antiviral flu treatment with a novel mechanism in nearly 2 decades.

On September 1, 2019, at the OPTIONS X Congress in Singapore, investigators from Genentech announced favorable results from 2 phase 3 trials of baloxavir marboxil, MINISTONE-2 and BLOCKSTONE, in a late-breaking session.

MINISTONE-2

The MINISTONE-2 study was a phase 3 trial that evaluated the pharmacokinetics and efficacy of 1 dose of baloxavir marboxil compared with oseltamivir in children <1 year to 12 years of age.

For the study, otherwise healthy children were enrolled into 2 parallel cohorts: patients 1 to <5 years and 5 to <12 years. Following randomization, the participants were randomly assigned to receive 1 dose of baloxavir marboxil or oseltamivir twice a day over a 5-day period.

The primary end point of the multicenter, randomized, double-blind study was the proportion of participants who experienced adverse events (AE) or severe AE up to day 29. The study met its primary end point with 46.1% of patients in the baloxavir marboxil arm experiencing at least 1 AE compared with 53.4% of participants in the oseltamivir arm.

Baloxavir marboxil successfully reduced the length of viral shedding by more than 2 days when compared with oseltamivir (median: 24.2 hours vs 75.8 hours, respectively). Additionally, baloxavir marboxil was found to be comparable to oseltamivir regarding secondary end points including time to alleviation of influenza signs and symptoms (median: 138.1 hours vs 150.0 hours, respectively).

Based on these results, the investigators conclude that baloxavir marboxil was well-tolerated and is an effective potential treatment for influenza in otherwise healthy pediatric populations.

BLOCKSTONE:

The phase 3 BLOCKSTONE trial was a randomized, post-exposure prophylaxis study that evaluated a single dose of baloxavir marboxil compared with placebo as a preventive treatment for individuals living with someone with an influenza infection confirmed by a rapid influenza diagnostic test.

The study was conducted by Shionogi & Co., Ltd during the 2018-19 influenza season in Japan and enrolled adult and pediatric participants. For the study, the participants were randomized to receive either a single dose of baloxavir marboxil or placebo as a preventive measure against developing the flu.

The primary end point of the study was to evaluate the proportion of participants who tested positive for the flu and had a fever and 1 or more other symptoms of influenza between day 1 and 10. Secondary end points were clinical efficacy, pharmacokinetics, and safety and tolerability.

According to results, preventive treatment with baloxavir marboxil significantly reduced the risk of developing the fly by 86% when compared with placebo. The results demonstrate that 1.9% of baloxavir marboxil-treated individuals had the flu compared with 13.6% in the placebo-treated group (p<0.0001)

“This benefit with baloxavir marboxil remained statistically significant versus placebo regardless of influenza A subtype (H1N1: 1.1% versus 10.6%, p=0.0023; H3: 2.8% vs 17.5%, p<0.0001),” Genentech said in a press release announcing the study results.

The benefit was also observed in contacts at high risk of flu-associated complications (2.2% vs 15.4%, p = -.0435), and children under 12 years of age (4.2% vs 15.5%, p = 0.0339) who are more vulnerable to influenza development.

Overall, baloxavir marboxil had a comparable safety profile over placebo with an overall incidence of adverse events being 22.2% for baloxavir marboxil and 20.5% for placebo. No serious adverse events were reported for the study drug.

Baloxavir marboxil is being evaluated in phase 3 development for children under the age of 1 year, severely ill individuals, people hospitalized with the flu, and is also being explored in reducing flu transmission.

Roche Group, which includes Genentech, is seeking supplemental New Drug Application for 1 dose oral treatment for people at high risk of complications from the flu. The decision is expected by November 4, 2019.