Drug maker Actelion has indicated that the company’s Food and Drug Administration (FDA)–approved pulmonary arterial hypertension (PAH) drug Bosentan, which is also known under the brand names of Actelion and Tracleer, recently failed a key FDA postmarket test. The test, which was part of the postmarket COMPASS 2 trial, revealed that Bosentan did not reduce time to first morbidity or mortality compared with a placebo.
According to a recent news release, Bosentan, which is endothelin-receptor blocker, has been approved as an oral therapy for pulmonary arterial hypertension since 2001, and was the first of its kind that could be taken by mouth — an achievement that made the treatment a viable choice for ensuring patient compliance. Since then approvals from the FDA for Bosentan as a treatment for other indications have come over the past decade.
As part of the COMPASS 2 trial, 334 patients with PAH randomly received either Bosentan or placebo, along with sildenafil (Revatio, Pfizer) treatment. The prevailing belief was that the use of Bosentan would yield a 43% relative risk reduction when added on to the sildenafil regimen. This endpoint was not reached in the postmarket trial.
While drug treatments for diseases are required to go through a series of exhaustive clinical trials by the FDA before being accepted for use in the general public, the FDA also asks for some drugs to be tested even after approval in what is called a postmarket clinical trials. according to the FDA website, “Postmarketing study commitments are studies required of or agreed to by a sponsor that are conducted after FDA has approved a product for marketing. FDA uses postmarketing study commitments to gather additional information about a product’s safety, efficacy, or optimal use. Agreements with sponsors to conduct post marketing studies can be reached either before or after FDA has granted approval to a sponsor to market a product.”
While the news was not good for PAH patients or Actelion, the company did note that, “while the study failed to meet its primary end point, an “exploratory analysis” suggested that patients taking bosentan on top of sildenafil showed an improvement of 21.8 m in 6-m-walk distance at week 16 (p=0.01).” Since pulmonary arterial hypertension remains an incurable disease with a high rate of mortality, the need for viable treatments is critical to the patient population. There is some promising news for PAH sufferers, however, as the FDA has approved two new agents for the treatment of the disease — macitentan (Opsumit, Actelion) and riociguat (Adempas, Bayer).