Actelion Pharmaceuticals has filed a request with the European Medicines Agency for the expanded approval of Opsumit (macitentan) as a treatment for adults with moderate to severe inoperable chronic thromboembolic pulmonary hypertension (CTEPH), the company announced.
If the EMA approves the submitted type II variation to the current label, Opsumit will become the first endothelin receptor antagonist (ERA) available in the European Union for inoperable CTEPH treatment.
In April, the company requested Opsumit’s label expansion with the U.S. Food and Drug Administration as a CTEPH therapy to improve exercise capacity and pulmonary vascular resistance (PVR), which is the resistance that must be overcome to push blood through the lungs.
Opsumit is currently approved for the treatment of pulmonary arterial hypertension (PAH).
“Building on its 20-year heritage of unprecedented innovation in pulmonary hypertension, Actelion is committed to addressing the unmet needs that persist in this severe and life-limiting disease,” Martin Fitchet, MD, global head of research and development at Actelion, said in a press release. “Ultimately our vision is to transform pulmonary hypertension into a chronic, manageable condition.”
CTEPH is characterized by progressive tissue scarring surrounding unresolved blood clots in the lungs, leading to a blockage or narrowing of the arteries. With surgery, it is possible to remove the abnormally developed tissue, a strategy that can potentially cure the condition. However, surgery is not an option for up to 50% of CTEPH patients whose treatment relies on Adempas (riociguat), the only therapy approved for this disease.
Opsumit’s label expansion request was supported by data from the Phase 2 MERIT-1 clinical trial (NCT02021292).
The trial included 80 patients with inoperable CTEPH who received a daily oral dose of 10 mg of Opsumit or a placebo. Participants with a more severe disease status were allowed to also receive background therapy during the study to manage PAH.
After 16 weeks of treatment, Opsumit was found to significantly decrease the mean PVR by 27%, compared with 13% in the placebo group. This finding demonstrated that the treatment could effectively lower a patient’s lung blood pressure.
By week 24, Opsumit-treated patients also had better exercise capacity, demonstrated by an average increase of 35 meters in the six-minute walk distance test from the start of the study.
The benefits of the therapy were evident, regardless of other background therapies taken by the patients.
Opsumit was generally well-tolerated by the CTEPH population, with a safety profile similar to that reported in previous clinical studies with PAH patients. The most common adverse events reported were edema (accumulation of fluid) and decreased hemoglobin.
“MERIT-1 provides the first randomized controlled trial data involving patients on monotherapy and combination therapy, addressing a key unmet need in CTEPH,” Fitchet said. “If approved, Opsumit has the potential to become a valuable treatment option in inoperable CTEPH.”