Endothelin-receptor antagonists (ERAs), recently discussed on Pulmonary Hypertension News as being effective for treating pulmonary hypertension, have been a standard part of clinician’s portfolios along with phosphodiesterase type 5 inhibitors and calcium channel blockers. The common definition for “treating pulmonary hypertension” is usually set by improvements in six minute walking distance (6MWD), and these three drug types have all shown significant benefits on 6MWD.
While excitement over new drugs such as riociguat (Adempas) suggests other drug types may be of benefit to pulmonary hypertension patients, the novel ERA macitentan, marketed by Actelion as Opsumit, reinforces the fact that standard therapies have become standard for a reason.
Macitentan was under evaluation in the Phase 3 clinical trial SERAPHIN. The study was unique in that it tested not only 6MWD but also patient-relevant outcomes. Cardiopulmonary haemodynamics, morbidity, and mortality were evaluated during SERAPHIN, and the two doses of macitentan delivered (3 and 10 mg) demonstrated significant improvements in all reported parameters. According to Dr. John Granton, Director of the Pulmonary Hypertension Program at Toronto General Hospital, “Both doses produced a reduction in peripheral vascular resistance and increase in cardiac output compared to placebo.” Dr. Granton spoke in a news article on MedNet, entitled, “Pulmonary Hypertension: New Therapies in Chronic Thromboembolic Pulmonary Hypertension and Pulmonary Arterial Hypertension,” produced after the Annual Congress of the European Respiratory Society.
Importantly, clinicians such as Dr. John Swiston, Director of the Pulmonary Hypertension Program at Vancouver General Hospital, would consider prescribing macitentan to their patients. “I would consider macitentan for category 1 PAH patients, WHO functional class II or greater,” said Dr. Swiston. Class identifiers were recently explained on Pulmonary Hypertension News by Contributing Editor Charles Moore.
The uniqueness of the SERAPHIN trial design “will have a significant impact on future clinical trials in PAH by demonstrating that it is feasible to perform studies with greater clinical relevance,” said Dr. Swiston. As haemodynamic outcomes are the primary factor important in the quality of life of pulmonary hypertension patients, they are key to study as primary endpoints. “This trial design aligns with recommendations from several PAH scientific bodies, specifically that the effect of novel medications on patient relevant outcomes, over a longer period of observation, need to be completed. This trial will likely become the benchmark for future trials in PAH,” concluded Dr. Granton.