With a second positive phase III study in the bag, Roche’s new influenza antiviral looks odds-on to receive a green light from US regulators later this year. A decision on baloxavir marboxil is due by December 24, and the Swiss pharma giant will be hoping for timely news so it can launch for the next flu season.
This outcome would be also good news for Shionogi, which discovered baloxavir and already sells it in Japan – the product is expected to become the Japanese firm’s biggest revenue generator by some margin. However, as is often the case nowadays, the biggest challenge lies with payers, who will need convincing that this novel entrant is better than cheap incumbents.
The most important of these are generic versions of Tamiflu, another Roche drug that was once a fairly substantial product for the company. As such it is quite surprising that sellside analysts covering Roche have yet to publish numbers for baloxavir – conceivably these are wrapped up in Tamiflu sales at this stage.
|Top-selling flu treatments|
|Annual sales WW ($m)|
|Xofluza (Japan sales only)||Shionogi||-||22||191||328|
|Pimodivir (phase III)||Johnson & Johnson||-||-||-||75|
|Tamiflu generic||Amneal Pharmaceuticals||-||30||33||40|
|Tamiflu generic||Hanmi Pharmaceutical||-||19||23||28|
|Total WW market (incl. others)||1,378||941||715||821|
Demand ebbed and flowed for Tamiflu with the severity of the flu season, but in peak years the drug was a blockbuster. In 2006, its most successful year on the market, it generated annual sales of just over $2bn and since launch in 1999 has made over $15bn in revenues for Roche, according to EvaluatePharma.
This is despite the neuraminidase inhibitors, of which Tamiflu is the most successful, being considered only marginally effective. Uptake has also been hampered by the narrow window in which they must be taken: within 48 hours of symptom onset.
New and different?
Baloxavir employs a different mechanism of action – it is a cap-dependent endonuclease inhibitor – and requires only one pill to be taken. It too needs to be taken within 48 hours of a flu diagnosis, and in these cost-conscious times Roche will need more than a convenience argument to win preferable treatment over generics.
The evidence so far is encouraging. Roche has released information from two trials, Capstone 1 and Capstone 2, though the latter, announced today, has only been toplined. Both trials contained arms of baloxavir, placebo or Tamiflu, though for the primary endpoints baloxavir was only pitted against a sugar pill.
Of Capstone 2, which was conducted in patients at high risk of complications, all Roche has said so far is that baloxavir significantly reduced the time to improvement of symptoms versus placebo. In Capstone 1, which recruited healthy patients, time to alleviation of symptoms was significantly shorter in the baloxavir group – a median of 53.7 hours was recorded, versus 80.2 hours for placebo patients.
On secondary measures baloxavir was pitted against Tamiflu, and for Capstone 2 it is not immediately clear whether these hit statistical significance – Roche’s press release only says “superior efficacy” was seen on measures such as viral shedding time and reducing viral load.
Capstone 1 did generate some convincing wins against Tamiflu – baloxavir patients stopped being infectious (viral shedding) significantly quicker and experienced a much faster drop in temperature.
Roche was allowed to file baloxavir on the basis of one phase III trial because of the urgent need for new options for very sick flu patients. But what is good enough for regulators is frequently not good enough for payers, at least not for a broad patient base. The full results of Capstone 2 need close scrutiny – and then perhaps the sellside can start coming up with some numbers.
|Shionogi's biggest sales-growth drivers|
|Annual revenues ($m)|
|Total (incl. others)||1,104||1,243||1,181||1,252|
|*figures include sales and royalties from Roche. Source: EvaluatePharma|