FDA Approves Bosentan for Treating Early-Stage PAH

Yael Waknine

August 13, 2009

August 13, 2009 — The US Food and Drug Administration (FDA) has approved an expanded indication for bosentan (Tracleer, Actelion, Ltd) for the treatment of mildly symptomatic World Health Organization (WHO) functional class 2 pulmonary arterial hypertension (PAH).

The approval was based on data from the pivotal phase 3 Endothelin Antagonist Trial in Mildly Symptomatic PAH Patients (EARLY) study, demonstrating a 22.6% reduction in pulmonary vascular resistance and a 77% decrease in clinical worsening for bosentan vs placebo at 24 weeks (P < .0001 and P = .011, respectively). In the study, more patients receiving bosentan remained stable with no deterioration of WHO functional class (13.2% vs 3.4%; P = .029).

Although increases in 6-minute walk distance did not reach statistical significance (P = .076), the company notes that most enrolled patients had a relatively well-preserved exercise capacity at baseline, rendering improvements difficult to ascertain.

"PAH is a progressive and devastating disease, and patients are not always treated as early as they should be with therapies that can impact disease progression," said Vallerie McLaughlin, MD, associate professor of medicine and director of the Pulmonary Hypertension Program, University of Michigan Health System, in a company news release. "The approval of Tracleer for the treatment of patients with early-stage disease offers physicians a new, proven therapy that may result in beneficial clinical outcomes."

The FDA notes that clinicians should consider whether the benefits of bosentan therapy offset the risk for liver injury when treating patients with WHO functional class 2 PAH; early liver injury may preclude future use as the disease progresses. As is required for all bosentan-treated patients, liver function tests should be obtained before treatment initiation and monthly thereafter.

Bosentan, a dual endothelin-receptor antagonist, previously was approved to improve exercise capacity and reduce clinical worsening in WHO functional class 3 and 4 PAH patients.