When given alone or in combination with other therapies, Opsumit (macitentan) leads to clinically meaningful improvements in right heart function in people with pulmonary arterial hypertension (PAH), according to data from a final analysis of a Phase 4 trial.
Findings were announced in the presentation “Results from the REPAIR Study: Effects of Macitentan on Right Ventricular (RV) Remodelling in Pulmonary Arterial Hypertension (PAH),” at the virtual education platform of the International Society for Heart and Lung Transplantation (ISHLT).
The effects of Opsumit on right ventricular (RV) function and hemodynamic (blood flow) properties in 87 symptomatic PAH patients were investigated in a multicenter, open-label, Phase 4 trial (NCT02310672) called REPAIR, sponsored by Actelion.
The ventricles are the two lower chambers of the heart. While the left ventricle is responsible for pumping blood out of the heart into the body, the right ventricle is responsible for pumping blood into the lungs.
REPAIR was the first PAH trial to use RV stroke volume (RVSV) as a primary endpoint. RVSV is a cardiac MRI parameter that measures the total amount of blood being ejected from the right ventricle when the heart contracts.
“Right ventricular dysfunction is an indicator of disease progression in PAH. This study represents the first time that right ventricular function, as determined by MRI, has been used as a primary endpoint in a multicenter PAH study,” Richard N. Channick, MD, a professor of medicine, co-director of the Pulmonary Vascular Disease Program, and director of the Acute and Chronic Thromboembolic Disease Program at UCLA Medical Center, told Pulmonary Hypertension News in an email exchange.
This endpoint allowed clinicians to further understand Opsumit affects the working and remodeling of the heart’s right ventricle, driven by the strain posed by high blood pressure in PAH patients.
REPAIR also evaluated changes to pulmonary vascular resistance (PVR; a measure of heart strain), right ventricle cavity volume, six-minute walk distance (6MWD; a measure of exercise capacity), and WHO functional class (a disease severity classification system).
Changes in all these measures were assessed from baseline (the beginning of the study) to week 26. Treatment with Opsumit lasted approximately one year (52 weeks).
Most patients (39%, 34 people) started treatment for PAH during this trial, given a combination of Opsumit and a vasodilator compound belonging to the class of phosphodiesterase type 5 inhibitors (PDE-5). About one-third (36%, 31) of patients were already on a stable treatment regimen with a PDE-5 inhibitor when starting treatment with Opsumit. The remaining one-fourth (25%, 22 people), also treatment naive like the first combo group, were started on Opsumit alone (as monotherapy).
A total of 71 patients, with valid RVSV and PVR assessments at baseline and at week 26 (6.5 months), were included in the study’s final analysis set.
Findings showed the RVSV increased by 12 mL at week 26, while PVR dropped by 38%, suggesting lesser heart strain.
Statistically significant improvements were also seen at week 26 in other parameters, including right ventricle cavity volume and mass, and 6MWD scores.
More than half (56.3%) of the patients at week 26 had shifted to a milder WHO functional class of disease severity, while 42.3% maintained their initial classification. The disease did not worsen in any patient over these months.
Importantly, improvements seen in RVSV and 6MWD scores at week 26 were maintained up to week 52, the end of the treatment period.
“The demonstrated effect of Opsumit on right ventricular function is important to clinicians as we know that right ventricular failure is the reason for deterioration and death in PAH,” Channick said.
Opsumit’s safety and tolerability profile was consistent with data from previous studies. Side effects were reported in 86% of study participants, with the most common being peripheral edema (swelling, 22%), headache (21%), dizziness (14%), and cough, lower hemoglobin counts, and upper respiratory tract infection (12% each). One patient died of cardiac arrest during the study.
“Results from the final analysis of the REPAIR study demonstrate the potential of Opsumit, as monotherapy or part of combination therapy, to improve outcomes for patients with PAH,” Channick said, noting that these data add “to the body of research advancing our understanding of the progression and management of this chronic and progressive disease.”
These data, he added, “provide insights into treatment response with Opsumit, and further our ability to deliver quality care for patients.”
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