Phase III macitentan data lift Actelion

Actelion got a major boost this week when it reported positive phase III results for macitentan, a follow-up to pulmonary arterial hypertension (PAH) blockbuster Tracleer which is being hit by competition.

Macitentan met the primary endpoint in the phase III SERAPHIN trial and is now on track for regulatory submissions before the end of 2012, said Actelion.

Net income at the Swiss pharma company plunged nearly 70 per cent in the first quarter of the year after competition to Tracleer (bosentan) from Gilead Sciences' Letairis (ambrisentan) helped drag down revenues by 21 per cent.

Tracleer is also due to lose patent protection in 2015, opening the door to generic competitors, and Actelion is hoping to get macitentan established in the marketplace well before then.

Both doses (3mg and 10mg) of macitentan that were tested in the 732-patient study decreased the risk of a morbidity/mortality event compared to placebo.

The endpoint was reduced by 45 per cent in the 10mg dose group and 30 per cent with the 3mg dose, which Actelion chief executive Jean-Paul Clozel described as "outstanding results".

PAH is a life-threatening disorder marked by abnormally high blood pressure in the arteries between the heart and lungs, which can lead to a dramatic loss in exercise capacity and heart failure.

The new agent is a dual endothelin (ET) receptor antagonist, with a broader spectrum of activity than Tracleer and greater tissue penetration.

That profile has prompted speculation among analysts that it could achieve peak sales of around 2.5bn Swiss francs ($2.8bn), a billion francs more than Tracleer's current annual turnover.

Market research firm Decision Resources has predicted that macitentan will earn a 20 per cent share of the US PAH market by 2019, thanks to the hard data on morbidity and mortality, a superior safety profile and lower risk of causing drug interactions compared with Tracleer, which has been linked to liver side effects.

"With this well-designed PAH study, Actelion pursued an ambitious goal to focus on outcome benefits as the primary endpoint," commented Lewis Rubin of the University of California, San Diego, a senior advisor on the SERAPHIN trial.

"The impressive results of this landmark study are setting a new standard in how to conduct studies in this devastating disease," he added.

Macitentan is also being tested in phase III as a treatment for ischaemic digital ulcers associated with systemic sclerosis, as well as in early-stage clinical trials for glioblastoma.