BioWorld International Correspondent

Actelion Ltd. lifted the lid on one of its undisclosed clinical development programs, revealing for the first time that the molecule named Actelion-1 is an endothelin receptor antagonist (ERA) and also that the molecule is moving into a Phase III program targeting pulmonary hypertension.

The news boosted the Allschwil, Switzerland-based company's shares by more than 7 percent Monday to close at CHF240.10 (US$199.66), up CHF16.10 from Friday's close.

Actelion also disclosed top-line results from a Phase II study in 379 patients with mild essential hypertension, which compared tolerability and efficacy of four doses of Actelion-1 with two comparators, placebo and the ACE inhibitor enalapril. A preliminary analysis, the company said, suggested that the two higher doses were "significantly better than placebo" and "better than enalapril" in reducing blood pressure 24 hours after drug intake.

The company plans initially to pursue pulmonary hypertension (PH), which has a larger patient population than that of pulmonary arterial hypertension (PAH), the condition for which its main drug franchise, Tracleer (bosentan), is approved. Literature estimates of PH incidence on OECD countries are between 250,000 and 300,000 cases per year, Actelion spokesman Roland Haefeli told BioWorld International, whereas the incidence of PAH is estimated at 100,000 to 150,000 cases per year.

Actelion will evaluate the impact of Actelion-1 on morbidity and mortality in PH, an effort that will take several years to complete. "Three to five years is in the realm of possibility," Haefeli said. "We are going for a larger indication with hard endpoints."

Actelion-1 is rationally designed to be more potent than Tracleer because of its tissue penetrance. "This is fundamental because endothelin is produced in the tissues and the endothelin receptors are located mostly in tissues," said Actelion's head of drug discovery, Martine Clozel. The company will reveal further details on this aspect of the molecule's mechanism of action at an R&D day in February.

The compound is, Haefeli said, a non-selective ERA antagonist, a feature it shares with Tracleer. "We've been long-term proponents [that] in chronic disease you have to use comprehensive blockade," he said. Potential competitors, ambrisentan, which Foster City, Calif.-based Gilead Sciences Inc. is developing, and sitaxsentan from Houston-based Encysive Pharmaceuticals Inc.., are both selective for the A-subtype endothelin receptor.

Denise Anderson, head of health care research at Kepler Equities in Zurich, Switzerland, upped her target price on the stock from CHF255 to CHF285 on the news. "I wanted it to be another indication," was her first reaction, she told BioWorld International. "Actually, when you look at it, it has the potential to be quite exciting," she added.

It has, she said, the potential to provide sales acceleration just as sales of Tracleer start to decay. "If they can really [show improvement in] morbidity/mortality, we don't have to worry about competition," she said.

Mike Booth and Karl Keegan at Canaccord Capital's London office were more bearish, and made no change to their current sell recommendation, with a target price on the stock of CHF185.