FDA approves the first new drug for the treatment of Influenza in nearly 2 decades

The U.S. Food and Drug Administration (FDA) today approved Roche Xofluza ™ (baloxavir marboxil) for the treatment of acute uncomplicated influenza (flu) in patients 12 years of age and older who have been symptomatic for no more than 48 hours.

 “This is the first new antiviral flu treatment with a novel mechanism of action approved by the FDA in nearly 20 years. With thousands of people getting the flu every year, and many people becoming seriously ill, having safe and effective treatment alternatives is critical. This novel drug provides an important, additional treatment option,” said FDA Commissioner Scott Gottlieb, M.D. “While there are several FDA-approved antiviral drugs to treat flu, they are not a substitute for yearly vaccination. Flu season is already well underway, and the U.S. Centers for Disease Control and Prevention recommends getting vaccinated by the end of October, as seasonal flu vaccine is one of the most effective and safest ways to protect yourself, your family and your community from the flu and serious flu-related complications, which can result in hospitalizations. Yearly vaccination is the primary means of preventing and controlling flu outbreaks.”

Influenza is a severe infectious disease worldwide with annual epidemics of 3 to 5 million cases of severe disease, millions of hospitalizations and up to 650,000 deaths worldwide.

Xofluza is a first-in-class, single-dose oral medicine and acts by inhibiting the polymerase acidic endonuclease, an enzyme essential for viral replication. It has shown efficacy against a wide range of influenza viruses, including oseltamivir-resistant strains and avian strains (H7N9, H5N1) in non-clinical studies.

The safety and efficacy of this single dose, antiviral drug Xofluza, was proved by the results of two randomized controlled clinical trials of 1,832 patients recently published in the 6 September 2018 issue of the New England Journal of Medicine. In phase III CAPSTONE-1 trial, participants were randomized to receive either Xofluza, a placebo, or another antiviral flu treatment within 48 hours of experiencing flu symptoms.

Xofluza significantly reduced the duration of flu symptoms by more than one day (median time 54 hours versus 80 hours; p<0.001) as compared to placebo. The efficacy was comparable to oseltamivir when it comes to duration of symptoms, but Xofluza significantly reduced the viral load 1 day after the start of therapy.

In the other phase 2 trial, the median time to alleviation of influenza symptoms was 23.4 to 28.2 hours shorter in the baloxavir groups than in the placebo group (P<0.05).

Thus, single-dose baloxavir was superior to placebo in alleviating influenza symptoms and was superior to both oseltamivir and placebo in reducing the viral load one day after initiation of the trial regimen in patients with uncomplicated influenza.

The most common adverse reactions in patients taking Xofluza included diarrhea and bronchitis, nausea, common cold symptoms (nasopharyngitis) and headache.

 FDA approved Xofluza under priority review, and the drug will be available across the U.S. in the coming weeks. Xofluza was discovered by Japanese drug maker Shionogi & Co., Ltd and was its 10mg/20mg tablets were approved by the Ministry of Health, Labour and Welfare in Japan in February 2018 for the treatment of Influenza Types A and B. 

The drug is being further developed and commercialized globally in collaboration with the Roche Group (which includes Genentech in the US). Under the terms of this agreement, Roche holds worldwide rights to Xofluza excluding Japan and Taiwan, which will be retained exclusively by Shionogi & Co., Ltd.

FDA press release

Roche press release

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Novel flu drug that kills the virus in 1 day get clearance in Japan

Japanese pharmaceutical company Shionogi claims that treatment with baloxavir marboxil, effectively kills influenza A and B virus in just 24 hours as opposed to the current user oseltamivir (sold under the brand name Tamiflu), which takes 72 hours to kill the virus.

Japan’s health ministry recently approved the drug and will be sold under the brand name Xofluza.

This is a welcome announcement in healthcare and pharma industry, in the midst of worst Flu season that the USA has experienced. Probably it could make the next flu season safer.  

Baloxavir marboxil prevents the replication of the virus by cap-dependent endonuclease activity of the viral polymerase unlike the existing drug oseltamivir (Tamiflu, Genentech), which acts by inhibiting the neuraminidase enzyme.

It’s prescription as single dose treatment irrespective of age greatly improves patients’ compliance as opposed to the twice-daily dose of oseltamivir for 5 days.

Baloxavir marboxil was tested in a randomized, double-blind, parallel-group, multicenter, placebo- and active-controlled study (CAPSTONE-1), which enrolled 1,436 otherwise healthy patients diagnosed with influenza. 

These patients with age between 20-64 years were randomized in a ratio of 2:1:2 to receive a single 1-time oral dose of 40 or 80 mg of baloxavir marboxil based on body weight or a placebo, or 75 mg BID of oseltamivir for 5 days.

Patients between 12-19 years of age were given baloxavir marboxil based on body weight. Those who weighed less than 80 kg received 40 mg of the drug while patients weighing more than 80 kg were given 80 mg.

The trial results showed that:

•   Patients who received Baloxavir marboxil had significantly lower viral titer at 1, 2 and 4 days
• Viral shedding in Baloxavir marboxil group was significantly less at 24 hours as compared to 72 hours in patients on oseltamivir and 96 hours in patients on placebo.
• The patients in the study group were afebrile in 24 hours vs 42 hours in the placebo group.
• The time to alleviation of symptoms (TTAS) was significantly shortened in the study group (53.7 hours) vs (80.2 hours) in the placebo group (p<0.0001). 
• The new drug was also well tolerated with significantly fewer side effects (20.7%) as compared to placebo (24.6%) or oseltamivir (24.8%).  

Shionogi is currently conducting another phase 3 trials with the drug in patients who are at high risk for Influenza.

Following the approval by Japanese health ministry in February, the drug could be on sale in Japan as early as May.

The head of co-developer Roche's pharma unit, Daniel O'Day, told Bloomberg, "The advantage is that it's one pill once, versus a course of therapy, so particularly for pandemic planning, this could be an advantage, you don't have the potential resistance that comes with not completing your course of therapy."

Shionogi and the Tamiflu maker Roche share the rights to sell Baloxavir marboxil in international market, but it will be almost a year before the drug enters US market.

Shionogi News Release