A pair of phase 3 trials show the single-dose oral drug could have expanded benefits for influenza, just months before an sNDA ruling.
Single-dose baloxavir marboxil (XOFLUZA) has presented positive findings for influenza (flu) treatment in a pair of phase 3 trials released just months before the US Food and Drug Administration (FDA) is set to rule on the oral therapy.
In findings from the MINISTONE-2 and BLOCKSTONE phase 3 studies, presented this weekend at the Options for the Control of Influenza (OPTIONS X) meeting in Singapore, Genentech shared data showing the only single-dose oral flu therapy on the market is beneficial for pediatric flu versus oseltamivir, and preventive for household members living with someone diagnosed with the flu.
In the MINISTONE-2 trial, investigators assessed baloxavir marboxil versus oseltamivir (Tamiflu) in children aged 1-12 years old with the flu. The team sought a primary endpoint of adverse events (AEs) or severe AEs for up to 29 days.
Their findings showed baloxavir marboxil is well-tolerated and efficacious in children, with just 46.1% of treated patients reporting at least 1 treatment-emergent AE versus 53.4% of patients administered oseltamivir.
Investigators also reported a reduced length at least 2 days of flu virus being continually released from the body in patients administered baloxavir marboxil versus oseltamivir (median viral shedding time 24.2 hours vs 75.8 hours). The oral therapy also showed comparable efficacy to the competitor drug, and reported a safety profile consistent with previous findings.
Of the 4 positive phase 3 studies for baloxavir marboxil, this was the first global assessment in children, and included a patient population of otherwise healthy children.
In the BLOCKSTONE trial, investigators conducted a randomized, post-exposure prophylaxis assessment that observed single-dose baloxavir marboxil versus placebo in adults and children living with someone infected with the flu, as confirmed by a rapid diagnostic test.
Conducted during the 2018-19 flu season in Japan, BLOCKSTONE assessed for a primary endpoint of proportion of participants who tested positive for the flu virus and had a fever—plus 1 or more respiratory symptoms—between 1-10 days of treatment.
Baloxavir marboxil significantly reduced patient risk of flu development by 86% versus placebo—just 1.9% of treated patients developed the flu, versus 13.6% of placebo-treated patients.
Patient benefit from prophylaxis therapy remained statistically significant regardless of influenza A strain subtype, and remained significant in both people at high risk of flu-associated complications and children younger than 12 years old. Baloxavir marboxil had a comparable safety profile to placebo, with overall AE incidence being reported in 22.2% of treated patients and 20.5% of placebo patients.
Sandra Horning, MD, chief medical officer and head of Global Product Development for Genentech, said the BLOCKSTONE findings give encouragement to the company, as they have now shown effective preventive capability with the oral therapy.
“As the influenza virus can rapidly infect those around us, limiting the spread of infection within households potentially avoids a significant impact on the wider community — a critical step in the global fight against the flu,” Horning said in a statement.
Both MINISTONE-2 and BLOCKSTONE findings complement the consideration of baloxavir marboxil as a drug for high-risk flu complications. Genentech’s supplemental New Drug Application (sNDA) to the FDA for this indication was accepted earlier this year, and will be ruled on by November 4.
XOFLUZA was previously approved by the FDA as an acute, uncomplicated flu therapy in patients aged 12 years or older in October 2018. Along with the pursuit for an indication which expands its availability to high-risk patients, Genentech is interested in expanding the drug’s clinical availability to younger populations.
“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,” Horning said.