March 17th, 2014

Phase 4 Actelion Study Misses Primary Endpoint

Actelion announced today that a phase 4 study with its blockbuster drug bosentan (Tracleer) had failed to meet its primary endpoint.

The COMPASS-2 trial was a prospective, randomized, double-blind, placebo-controlled trial evaluating the effect of bosentan on the time to first confirmed event in patients with symptomatic pulmonary arterial hypertension (PAH) already receiving treatment with sildenafil.

According to the company, a 17% risk reduction in the primary endpoint of the time to first event did not reach statistical significance (p=0.25). Actelion reported that an exploratory analysis showed a significant increase in the 6-minute walking distance in the combination group and “and a placebo-corrected incidence of 15.4%” in elevated liver enzymes over 23 months of treatment.

The press release quoted the University of Michigan’s Vallerie McLaughlin, chair of the trial’s steering committee: “While the observed risk reduction of 17% did not reach statistical significance, I am convinced that this study provides important information for the scientific community and we are committed to perform all the necessary analyses to fully understand the outcome of the study.”

The company said that the full results of the study will be presented at future congresses and in peer-reviewed publications.

John Ryan, a pulmonary hypertension expert at the University of Utah, offered the following perspective:

“The COMPASS-2 trial assessed the efficacy of a common clinical practice, namely the addition of bosentan (an endothelia receptor antagonist, ERA) to patients with pulmonary arterial hypertension (PAH) already taking sildenafil (phosphodiesterase 5 inhibitor, PDE5i). The safety and benefit (or otherwise) of this combination therapy has been largely unknown. But because this disease process can advance so rapidly with a limited life expectancy, if patients are deemed to be failing monotherapy with clinical deterioration, most PAH providers are aggressive in adding on a second agent. Therefore the COMPASS-2 trial represents a marked advance in our knowledge of the merits of dual therapy. Looking forward, it will be important to perform similar combination trials with the other classes of agents available, especially ERAs and the new soluble guanylate cyclase stimulators (riociguat being the only currently available agent).”

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