Selexipag hit puts Actelion back on the buyout radar
With the pivotal Griphon trial of selexipag delivering a strongly positive result Actelion’s plan to dominate the pulmonary arterial hypertension market is in place, making United Therapeutics’ bid for glory look like a brief aberration.
Not only will selexipag bolster Actelion’s own franchise, it also looks to have broken United’s hold on the prostacyclin part of this space. Actelion is no stranger to takeover speculation, and the Griphon data undoubtedly raise the question of how long the group can remain a standalone entity.
Actelion was once seen as a one-trick pony whose success depended on its first pulmonary arterial hypertension (PAH) entrant, Tracleer, but it has managed the lifecycle perfectly. With Tracleer facing patent expiry next year the Swiss group secured approval last October for its follow-up, Opsumit, on the basis of the Seraphin trial showing a 45% cut in morbidity or mortality.
Now the trick has been repeated with selexipag, an oral prostacyclin agonist that in Griphon decreased risk of morbidity or mortality – its primary endpoint – by 39% versus placebo, with high statistical significance (p<0.0001). Tracleer failed to show a mortality benefit, but given Opsumit's and now selexipag's successes this hardly seems to matter.
Actelion already sells the prostacyclin analogues Veletri (injected) and Ventavis (inhaled), and with the oral agent’s success it now has United in its sights. Orenitram, an oral form of United’s prostacyclin analogue Remodulin, received a surprise US approval in December, and the US group sells an inhaled form, Tyvaso (A Christmas miracle for United as oral Remodulin approved, December 23, 2013).
Expectations for Orenitam are low, and its label cites a “small” treatment effect, so for selexipag this is an easy target. Moreover, safety issues limit Orenitam to monotherapy, whereas PAH treatment is evolving into combinations, and indeed Actelion highlights the fact that 80% of Griphon patients were on background therapy, meaning Tracleer, a PDE5 inhibitor like Revatio, or a combination.
United’s inhaled Tyvaso, which sold $439m last year, is a more important target for Actelion to eat into. Consensus forecasts expect Tyvaso to grow at almost an 8% CAGR over the next five years, and this is surely now unsustainable.
The fear of United’s investors was reflected in the stock market on Friday – before the Griphon data were formally announced – as United’s shares drifted down 8%, though curiously today they rose 2% in early trade. Still, the factors that could map selexipag’s path to victory have not been disclosed, pending further analysis of Griphon.
For instance, Actelion would not say whether mortality or morbidity drove the composite primary endpoint; the distinction could be important as a mortality reduction indication for selexipag would be a huge win. Opsumit is indicated for delaying PAH progression, though the Seraphin morbidity/mortality data are on its label.
Another issue is tolerability; in Griphon twice as many patients (14%) treated with selexipag withdrew owing to side effects versus placebo, though it is not yet known whether this was statistically significant. On a call Actelion said it had expected many more discontinuations given the length of the trial, which started dosing in 2009.
EvaluatePharma estimates that Selexipag will generate $365m of revenue in 2020, and forecasts will no doubt now rise; Bryan Garnier analysts, for instance, said the drug could hit $1bn in sales, with a 5% cost of goods and 15% royalty to its originator, Nippon Shinyaku.
With Actelion’s stranglehold on PAH virtually assured the key issue now must be whether its market cap, combined with a typical 30% takeover premium, has already made it too expensive to buy. The stock was up 15% today, valuing the company at $12.9bn – a record high.
By European standards Actelion certainly does not look cheap. But the Griphon data will surely focus the mind of any company that had been tempted to take a look back in October.
|Griphon||1,156 PAH patients, vs placebo||NCT01106014|