Actelion Pharmaceuticals submitted a supplemental new drug application to U.S. regulatory authorities seeking expanded approval for Opsumit (macitentan) to treat inoperable chronic thromboembolic pulmonary hypertension (CTEPH).
The U.S. Food and Drug Administration application is based on promising results from the Phase 2 MERIT-1 clinical trial (NCT02021292) that evaluated Opsumit in patients with inoperable CTEPH.
Participants in the global MERIT-1 trial have the option of continuing Opsumit therapy in an extension study, called MERIT-2 (NCT02060721), which is expected to be completed in December 2020.
The preferred treatment for CTEPH is a surgery called pulmonary thromboendarterectomy. But about 40 percent of CTEPH patients are not candidates for that surgery due to either the nature of the disease, the location of the obstruction in the lung artery, or to the presence of other diseases.
Results of the Phase 2 trial were presented at the ATS (American Thoracic Society) 2017 International Conference and the ERS (European Respiratory Society) International Congress 2017.
The findings also were in the article “Macitentan for the treatment of inoperable chronic thromboembolic pulmonary hypertension (MERIT-1): results from the multicentre, phase 2, randomised, double-blind, placebo-controlled study,” published in October 2017 in the journal Lancet Respiratory Medicine.
MERIT-1 included 80 patients with inoperable CTEPH who received either Opsumit or placebo. Some of the participants also received background therapy for pulmonary arterial hypertension (PAH).
After 16 weeks, mean pulmonary vascular resistance (PVR) decreased to 73% of baseline in the treated group compared to a decrease of 87.2% in the placebo group. PVR is used to measure the severity of hypertension in the pulmonary artery, which transports blood to the lungs.
At 24 weeks, the treated group walked an average of 35 meters (about 38 yards) more in the six-minute walk distance test (6MWD, a measure of exercise capacity) than they could at the start of the study. In the placebo group, there was an average increase of one meter.
Safety was consistent with Opsumit’s profile in other clinical trials, and adverse events were mainly peripheral edema, or swelling in the limbs (23% compared to 10% in the placebo group) and decreased hemoglobin (15%).
“Inoperable [CTEPH] is associated with a poor prognosis if left untreated,” Martin Fitchet, MD, the global head of research and development at Actelion, said in a press release.
“At Actelion, we are committed to advancing therapies for pulmonary hypertension patients around the world and we believe that this application may provide a new therapeutic option for those living with inoperable CTEPH in the United States,” he said. “With this latest milestone, Actelion is continuing to build on its 20-year legacy of groundbreaking innovation in this life-limiting disease.”
Opsumit is approved in the U.S. for the treatment of pulmonary arterial hypertension (PAH) to delay the progression of disease and hospitalization.