Roche claims US approval for novel flu treatment

The US FDA has given a green light to a new influenza treatment from Shionogi and Roche that has the first new mechanism of action in more than two decades.

Xofluza (baloxavir marboxil) is a cap-endonuclease inhibitor that interrupts a mechanism used by the virus to hijack the messenger RNA transcription system in cells, switching off virus production.

The drug represents Roche’s attempt to recapture a lucrative flu franchise afforded by its neuraminidase inhibitor Tamiflu (oseltamivir), which started to decline when its drug lost patent protection in 2016. By that point, it had generated almost $20bn in revenues since its first launch in 1999, driven in part by governments stockpiling the drug in case of a flu pandemic.

Tamiflu continues to make useful sales – contributing $333 million to Roche’s coffers in the first nine months of this year – but that is a far cry from the $3 billion in sales it enjoyed at its peak, before generics entered the market.

The jury is out about Xofluza’s chances of reaching those heights, because while the drug was able to shorten the time to alleviation of symptoms compared to placebo in the CAPSTONE-1 trial, there was no significant improvement over Tamiflu on that endpoint. Analysts have suggested that as a result there won’t be much pressure to stockpile the new drug, particularly as generic oseltamivir is so cheap and readily available.

Meanwhile, FDA Commissioner Scott Gottlieb also took the wind out of the new drug’s sails somewhat by remarking in a press release that "While there are several FDA-approved antiviral drugs to treat flu, they’re not a substitute for yearly vaccination", although he also said: "this novel drug provides an important, additional treatment option."

Xofluza does have some other advantages over Tamiflu, however. It is delivered as a single dose within 48 hours of symptom onset, while Tamiflu is recommended to be taken twice-daily for at least five days.

The new drug has also been shown to be effective against flu strains that develop resistance to neuraminidase inhibitors, which along with Tamiflu include GlaxoSmithKline’s inhaled Relenza (zanamivir) and Seqirus’ intravenous Rapivab (peramivir) in the US. However, the US Centres for Disease Control (CDC) says the vast majority of currently circulating influenza viruses are sensitive to these medications.

Roche and Shionogi have data from another trial – CAPSTONE-2 – that shows Xofluza is of particular benefit in people at high risk of flu complications, significantly outperforming placebo on time to improvement, and that could help encourage take-up as there are no currently-approved flu medicines for this group.

The drug also topped both Tamiflu and placebo on curbing the levels of virus in the body and the length of time the virus continued to be released, which Roche says could reduce transmission rates, and seems to be better than Tamiflu at treating influenza type B.

Speaking on Roche’s third-quarter results call last week, Roche’s head of pharma Daniel O’Day said that he is "more and more convinced that this is a medicine that will improve on almost all aspects of Tamiflu going forward." The company plans to file the CAPSTONE-2 data with regulators, which could lead to a label update next year.

Roche has said it will launch Xofluza in the US at a price of $150 per dose, which is roughly the same as a five-day supply of generic oseltamivir. The drug was approved in Japan earlier this year, where it is sold exclusively by Shionogi, and is also due to be submitted for approval in Europe before the end of the year.

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