Roche has reported a second pivotal data on a novel influenza drug – baloxavir marboxil – that it says is the first drug with a new mechanism of action for the viral infection in almost two decades.
The oral, one-dose drug significantly reduced symptoms in people at high-risk of developing complications from the flu in the CAPSTONE-2 study, including people aged over 65 and those with other illnesses such as asthma, chronic lung disease, diabetes, or heart disease.
Roche already has positive data from a phase III trials of baloxavir marboxil in uncomplicated flu, and recently filed for approval with the FDA for that indication, setting up a possible approval in time for the 2019/20 flu season.
Flu remains a major cause of death worldwide, leading to severe disease in 3 to 5 million people every year and causing around 650,000 deaths.
In the new study, baloxavir marboxil met its primary objective of reducing the time to improvement of flu symptoms compared to placebo, and also cut the rate of flu-related complications, in vulnerable patients. It also achieved secondary objectives, including reducing viral shedding and the amount of virus in the body compared to placebo and also Roche’s established flu drug Tamiflu (oseltamivir).
Roche introduced its mainstay flu drug Tamiflu (oseltamivir) almost 20 years ago, and it has been a big earner for the company – in part fuelled by government stockpiling in case of a flu pandemic and despite spirited debate over its efficacy and controversy over access to clinical trials data.
Despite its age it added $535m to Roche’s coffers last year, albeit down a third over the prior year due to generic competition, but added another $292m in the first quarter of 2018 thanks to a particularly serious 2017/18 flu season.
With baloxavir marboxil Roche now looks like it could have a successor to keep its franchise going for the foreseeable future, and with better dosing. Tamiflu has to be dosed twice-daily for five days, while the new drug is delivered as a one-day, one-dose regimen. Also in its favour is that baloxavir marboxil is already on the market in Japan, where its originator Shionogi won approval earlier this year as Xofluza.
The drug works by works by inhibiting an enzyme known as cap-dependent endonuclease, which the flu virus relies on to penetrate human cells. In contrast, Tamiflu works by preventing infected cells from shedding viral particles. And that seems to make a big difference to the way flu infection progresses: in the earlier CAPSTONE-1 study, baloxavir marboxil shut down virus production after 24 hours, while it continued for 72 hours with Tamiflu and 96 hours with placebo.
“Baloxavir marboxil is the first antiviral to show a clinically meaningful benefit in people who are most susceptible to complications from the flu, including older people and those living with certain medical conditions,” said Sandra Horning, Roche’s chief medical officer.
“We plan to submit the results of this second positive phase III study for baloxavir marboxil to healthcare authorities, and look forward to discussing next steps since there are no current antiviral medicines approved to specifically treat this high-risk population.”