Roche just rolled out detailed late-stage data on its next-generation flu drug, showing it could be helpful for patients vulnerable to complications. But its performance against Roche’s now off-patent Tamiflu may hold it back as it goes up against cheap generics.
The drug, called baloxavir marboxil, is already marketed in Japan as Xofluza by its developer Shionogi. In a phase 3 trial dubbed CAPSTONE-2, it significantly reduced time in improvement of flu symptoms versus placebo—73.2 hours versus 102.3 hours—in people at high risks for serious complications, including older people and those living with medical conditions such as asthma and heart disease, among others.
But when compared with Tamiflu, Xofluza's 73.2 hours didn't meet the statistical significance benchmark for topping Tamiflu’s 81.0 hours. That outcome mirrors a similar one from the previous CAPSTONE-1 study in uncomplicated influenza, where the time to alleviation of symptoms wasn’t much different between the two drugs.
Still, both studies met their primary endpoints, which will form the basis for the FDA’s decisions. The agency is currently reviewing the drug’s use in the uncomplicated setting, with a decision set for Dec. 24. If approved, Xofluza would become the first flu medicine with a novel mechanism of action in nearly 20 years.
CAPSTONE-2 is the first phase 3 “to demonstrate a significant, clinically meaningful benefit in people at high risk for complications from the flu for which there are no currently approved medicines,” Sandra Horning, M.D., Roche’s chief medical officer and head of global product development, said in a statement.
However, not demonstrating superiority to Tamiflu when it comes to relieving symptoms make it difficult for Roche to fight some cheap generics that have rapidly eaten away Tamiflu’s sales; after all, symptom relief is what patients can directly feel.
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There are a few silver linings Roche played up in its announcement Thursday. For example, in the subpopulation of patients with influenza type B, where some other antivirals have shown limited efficacy or inconclusive data, Xofluza was significantly better than Tamiflu at cutting the time to symptom improvements, at 74.6 hours versus 101.6 hours to be specific.
It also showed superior efficacy compared to Tamiflu in some key secondary endpoints, including time to stop virus release from the body. That kind of fast virus-suppressing action could stop the virus from passing on to others.
Besides, as a one-time, single-dose therapy, Xofluza will be much more convenient for patients. In comparison, Tamiflu requires taking pills twice daily for five days.
Roche is counting on Xofluza to remedy Tamiflu’s loss to generics, as the company also faces existing or upcoming copycat challenges to its oncology blockbusters Herceptin, Avastin and Rituxan. In the first half of 2018, the decline in Tamiflu sales was partly offset by a strong flu season in the U.S. But still, sales dropped 11% to CHF 320 million ($323 million) over the six-month period.