FDA expands Xofluza approval as Roche struggles to catch looming flu market
As a potentially powerful flu season looms, so does a big test for Roche and its new flu drug, Xofluza. The Swiss giant just got a small boost in advance of that test as the FDA expanded Xofluza’s indication to include patients at high risk of developing flu-related complications.
Xofluza (baloxavir marboxil) was approved last October in the US, the first landmark flu drug approval in 20 years and a much-needed green light for a company that had watched its leading flu drug Tamiflu get eaten alive by generics. Like its predecessor, the pill offered a reduction in flu symptoms but not a cure.
Yet questions abounded, most notably about payers. Because despite Phase III trials showing it was far more effective than a placebo, Xofluza performed similarly to Tamiflu. For both drugs, symptoms endured for a median 54 hours after treatment in the PhIII CAPSTONE-1 trial. In CAPSTONE-2 Xofluza improved symptoms after 73 hours compared to Tamiflu’s 81.
Roche touted Xofluza’s convenience over Tamiflu: one dose over one day, rather than 10 doses over 5 days. It hasn’t been clear, though, how payers would weigh the ease of access when a generic can offer the same efficacy.
Roche tried to get ahead of that problem for last flu season with a special pricing model, offering a wholesale cost of $150, not much higher than the average sale price for Tamiflu but much higher than the lowest priced generics, and then offering a “coupon.” The coupon would knock $60 off the price for those without insurance and allow the insured to get the drug for as little as $30.
Genentech, which marketed the drug in the US for Roche, told Endpoints News the coupon would be offered again this year.
Other problems emerged last year, half a world away, where the drug was approved earlier and embraced as a “silver bullet” against the flu. In Japan’s healthcare system, Xofluza’s ease of use quickly made it the top flu drug on the market, WSJ reported in February. But in the midst of that flu season, Tokyo’s National Institute of Infectious Diseases said it had found that six strains of the virus had become drug-resistant.
This problem had to some degree been predicted. A New England Journal of Medicine editorial published a month before the drug’s US approval reviewed trial data and found the treatment led to “the emergence of viral escape mutants with reduced susceptibility.”
“The issue for public health is whether these influenza viruses with reduced susceptibility to baloxavir are transmissible,” wrote Timothy M. Uyeki, adding that early data indicated these strains might be less transmissible because they can’t replicate as easily.
In response to Japanese concerns, Genentech noted that the six identified strains wouldn’t meet the US standard of “resistant” because the drug still had some efficacy on them. At least one Tokyo doctor, though, reported that he stopped prescribing Xofluza because patients, misunderstanding the science, were worried they weren’t effective.
Roche reported $13 million in US revenue last year from Xofluza, and, as of September 10 $9 million in 2019.
For biotech nerds, the mechanism behind the drug may be as exciting as the drug itself. Rather than prevent the virus from spreading between cells, Xofluza blocks the virus from entering cells to begin with. It does so by inhibiting the “Cap-dependent endonuclease,” a part of the virus responsible for “cap-snatching” – a process where the virus steals the first 10-20 RNA residues of a host cell as part of a key process for viral invasion.