Roche's Novel Influenza Drug Xofluza Nears Approval in China

On April 25, the NMPA website showed that the review status of Roche’s new anti-influenza drug baloxavir marboxil tablets (Xofluza) marketing application (Acceptance No. JXHS2000074/75) has changed to “Under Approval,” indicating that this innovative anti-influenza drug with a novel mechanism of action is nearing its market launch in China.

Xofluza was developed by the Japanese pharmaceutical company Shionogi. In 2016, Roche entered into a collaboration agreement with Shionogi to jointly oversee the drug’s development outside Japan and Taiwan, with Roche holding commercialization rights in all regions except Japan and Taiwan.

In February 2018, Xofluza was first approved in Japan for the treatment of influenza caused by infection with influenza A and B virus strains; in October 2018, it received FDA approval for the treatment of acute, uncomplicated influenza in individuals aged 12 years and older.

Xofluza is a single-dose oral medication with a novel mechanism of action against influenza. As a cap-dependent endonuclease inhibitor, it targets the cap-dependent endonuclease enzyme in the influenza virus, which is essential for viral replication. Notably, Xofluza is the first anti-influenza drug approved in the United States in nearly 20 years.

Currently, the widely used oral anti-influenza medications are neuraminidase inhibitor antivirals (oseltamivir), which require twice-daily dosing for five consecutive days. In contrast, baloxavir (Xofluza), which features a novel mechanism of action, directly inhibits viral replication, allowing patients to cease viral shedding within 24 hours after a single dose throughout the entire course of the illness.

In a multicenter, randomized, double-blind Phase 3 clinical trial, enrolled participants were administered Xofluza, oseltamivir, or placebo. Clinical results demonstrated that the median time to alleviation of symptoms was shortened to 53.7 hours with Xofluza, comparable to that observed with oseltamivir (75 mg twice daily for 5 days), whereas it was 80.2 hours in the placebo group. The adverse reactions were consistent with those in the placebo group.

Furthermore, Xofluza is effective against oseltamivir (Tamiflu)-resistant strains of avian influenza viruses H5N1 and H7N9, rapidly eliminating the virus to promptly halt its transmission. In certain secondary endpoints, it even demonstrated superior efficacy compared to Tamiflu, including shorter times to cessation of viral shedding and reduction of viral load in the body.

Currently, baloxavir (Xofluza) has been approved in many countries and regions worldwide. In Japan, it is approved for the treatment of influenza A or B virus infections; in the United States, Singapore, Thailand, Hong Kong, and Taiwan, it is indicated for patients aged 12 years and older with acute uncomplicated influenza whose symptoms have appeared within no more than 48 hours.

On March 26, 2020, Genentech, a member of the Roche Group, announced that the U.S. FDA had accepted its New Drug Application (NDA) for Xofluza oral suspension single-dose granules (2 mg/mL), providing a more convenient option for children and individuals with difficulty swallowing. Meanwhile, the FDA also accepted two Supplemental New Drug Applications (sNDAs). One sNDA is for Xofluza to treat acute uncomplicated influenza in otherwise healthy children aged 1 year to under 12 years who have exhibited symptoms for no more than 48 hours. For both the oral suspension and the already approved tablets, the FDA accepted an sNDA for post-exposure prophylaxis of influenza in individuals aged 1 year and older. The FDA is expected to make decisions on these approvals by November 23, 2020.

According to the Insight database (https://db.dxy.cn/), baloxavir marboxil tablets were first approved for clinical trials in China in February 2019. Phase III clinical studies for influenza have been completed, and Phase I clinical trials for the treatment of influenza A or B virus infections have also been concluded. Baloxavir marboxil granules for suspension have also received clinical trial approval in China; however, no initiation of clinical trials has been identified to date.

How will this new drug be priced after its launch in China? Could a more affordable price be offered?

Note: The original text has been abridged.