SOUTH SAN FRANCISCO—Genentech, Inc. announced today that the U.S. Food and Drug Administration (FDA) has approved a supplemental New Drug Application for Xofluza (baloxavir marboxil) for the treatment of acute, uncomplicated influenza in people twelve and older who have been symptomatic for no more than 48 hours and who are at high risk of developing flu-related complications.
Xofluza is a first-in-class, one-dose oral medicine with a novel proposed mechanism of action that inhibits polymerase acidic endonuclease, an enzyme essential for viral replication. It has demonstrated efficacy in a wide range of influenza viruses, including in vitro activity against oseltamivir-resistant strains and avian strains (H7N9, H5N1) in non-clinical studies.
“With the flu season rapidly approaching, we can now offer Xofluza as the first and only FDA-approved treatment option indicated specifically for those at high risk of flu complications,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development at Genentech. “People with chronic conditions such as asthma, heart disease and diabetes are at higher risk of developing serious complications from the flu, so it is critical that these patients speak with their healthcare providers about possible treatment at the first signs and symptoms of the disease.”
The flu has the potential to cause a variety of complications, ranging from sinus or ear infections to more serious complications like pneumonia. This expanded indication for Xofluza was approved based on results from the Phase 3 CAPSTONE-2 study of a single dose of 40 mg or 80 mg of Xofluza compared to oseltamivir (75 mg twice daily for five days), or placebo in people twelve or older who met CDC criteria for being at high risk of complications from the flu.
Xofluza significantly reduced the time to improvement of flu symptoms compared to placebo, including in people infected with the flu type B virus. Adverse events (AEs) reported in at least 1% of adult and adolescent subjects treated with Xofluza included diarrhea (3%), bronchitis (3%), nausea (2%), sinusitis (2%) and headache (1%).
Xofluza is currently approved in several countries for the treatment of flu types A and B. In 2018, Xofluza was first approved by the FDA for the treatment of acute, uncomplicated flu in otherwise healthy people twelve and older who have been symptomatic for no more than 48 hours. Xofluza is also being studied further in a Phase 3 development program, including children under the age of one and severely ill, hospitalized people with the flu, as well as to assess the potential to reduce transmission of the flu from an infected person to healthy people.
In September, Genentech reported data from the Phase 3 MINISTONE-2 study which showed that one-dose Xofluza was a well-tolerated and effective potential treatment for the flu in otherwise healthy children aged one to less than 12 years old. Full results of the study were presented as a late-breaking abstract during the OPTIONS X 2019 congress in Singapore.
The study met its primary endpoint, which evaluated the proportion of patients with AEs or severe AEs up to study day 29, demonstrating results consistent with the safety profile of Xofluza. In Xofluza-treated participants, 46.1% experienced at least one treatment-emergent AE, compared to 53.4% in the oseltamivir arm. The study also showed the efficacy of Xofluza to be comparable to oseltamivir. Consistent with data in adults and adolescents, Xofluza also reduced the length of time that the flu virus continued to be released from the body by more than two days compared with oseltamivir (viral shedding; median time of 24.2 hours versus 75.8 hours, respectively).
“Each year approximately one in three children develop the flu, and their less mature immune systems mean they are slower to fight the infection and more vulnerable to complications. We are committed to developing new, more convenient treatment options for children with the flu and look forward to sharing these data with global health authorities,” mentioned Sandra Horning, M.D., chief medical officer and head of Global Product Development, in a press release.
Genentech also reported positive results in September from the Phase 3 BLOCKSTONE study, which showed that preventive treatment with Xofluza after exposure to an infected household member significantly reduced the risk of people developing the flu by 86% versus placebo. Full results of the study were also presented during the OPTIONS X 2019 congress.
The results show just 1.9% of Xofluza-treated household members had the flu, compared with 13.6% in the placebo-treated group. This benefit with Xofluza remained statistically significant versus placebo regardless of influenza A subtype (H1N1: 1.1% versus 10.6%; H3: 2.8% versus 17.5%).
The BLOCKSTONE study also demonstrated that even when fewer criteria were applied (proportion of participants with the flu, with fever or one or more respiratory symptoms), there was still a significant 76% reduction in the risk of household members developing the flu with Xofluza versus placebo (5.3% versus 22.4%, respectively).