Event - Astellas looks to hold onto UI franchise after adcom vote

Astellas’ efforts to build a urinary incontinence franchise have been aided by a positive vote for mirabegron from an FDA advisory committee. If approved by its June 29 PDUFA action date, the pill would help the Japanese group tap an important US revenue stream, helping to create a multibillion-dollar business worldwide.

A 7-4 verdict may be dampening optimism on a positive decision, however; concerns about increased heart rate and blood pressure raised by agency staff make it no sure thing especially given the comparatively benign cardiovascular safety profile of the marketed product. Any delay in approval will shorten the timelines to successfully achieve product switching before loss of Vesicare’s market exclusivity in 2018.

Company Astellas Pharma
Product Betanis (mirabegron)
Market cap $19.5bn
Product NPV $1.3bn
% of market cap 7%
Event type PDUFA
Date June 29, 2012

Franchise defence

Mirabegron is already sold as Betanis to treat overactive bladder in Japan, where it launched in September 2011 . The company reported domestic sales of JPY500,000,000 ($6.2m) through March; EvaluatePharma forecasts global sales of $785m in 2018, making it the company’s second-biggest growth driver.US sales of mirabegron represent slightly more than half of that; a European decision is also awaited later this year.

Combined with Vesicare, global sales of Astellas’ overactive bladder treatments will reach $2.31bn in 2018, giving the entire franchise a net present value of $4.4bn, more than one-fifth of the group’s market capitalisation.

Whilst it does not face an immediate patent expiry of Vesicare, Astellas no doubt would like to establish mirabegron well before that date. Successful product switching could enable the company to slowly ramp down its marketing effort for Vesicare well before 2018 and potentially accelerate the growth of mirabegron.

Bringing in the new

For a company that is forecast to see its Japanese co-promotion sales of Lipitor slashed in half of peak, to $604m, as well as having seen more than $1bn in sales and royalty revenue from Flomax significantly already reduced with its patent expiry, approvals of some new products with potential for significant growth will come in handy for Astellas.

Such a scenario is what analysts from Morgan Stanley are counting on. In a March 12 note, the broker’s slow-growth “bear” case assumes approval for mirabegron and two other products: MDV3100 and tivozanib, which Astellas will market globally and share profits in the US with the respective licensors, Medivation and Aveo Pharmaceuticals. Aveo and Astellas will also share profits in the European Union.

Medivation has impressed in prostate cancer (Medivation roars back to life as prostate cancer drug delivers, November 3, 2011), although tivozanib has yet to prove itself (Safety data crucial for Aveo to renew market faith, January 4, 2012). The minimum expectations in their bear case are for mirabegron sales of JPY 25bn ($308.7m) compared with a base case of JPY44.6bn ($550.8m) in 2016. A delay in US approval would likely force analysts to redo their assumptions on Astellas.

Beyond these three late-stage candidates, the Morgan Stanley analysts rate Astellas’ pipeline as “relatively weak.”

Mirabegron would be the first beta 3 adrenoreceptor agonist to treat overactive bladder; with the exception of Botox, the remaining market is largely dominated by muscarinic antagonists like Vesicare and Pfizer’s Detrol. As a novel mechanism of action in the indication, the regulator will tend to pay more attention to its safety; thus the concerns raised about elevated blood pressure.

The reduction in the number of incontinence episodes per day was statistically significant compared to placebo, but amounted to an average of 0.4, a point that some panellists brought up during the advisory committee meeting last week.

Combined with the safety questions – an increase compared to placebo in systolic blood pressure of 1mm and heartbeat of 1 per minute on average, along with liver safety in trials comparing mirabegron to Detrol – the regulator will have a difficult risk-benefit decision to make. Given the number of products on the market, this may be a situation where the four negative votes matter more to the regulator than the seven positive.

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