Opsumit (macitentan) failed to improve the cardiac function of people with pulmonary hypertension stemming from a heart problem, a Phase 2 clinical trial shows.
The PH patients who took it were also at increased risk of fluid retention, researchers said.
The therapy’s developer, Actelion, reported the results in the European Respiratory Journal. The article was titled “Macitentan in pulmonary hypertension due to left ventricular dysfunction.”
Heart failure stemming from right ventricle dysfunction is commonly accompanied by worsened PH.
Right ventricle dysfunction is associated with the development of a type of PH called post-capillary PH. Some patients can even develop post-capillary PH with components of another type of PH called pre-capillary PH. The hallmarks of this condition are high lung blood pressure and increased resistance to blood flow in the lungs, which doctors have linked to poor patient outcomes.
The U.S. Food and Drug Administration has approved a class of drugs known as endothelin receptor antagonists for treating PH. Researchers have been looking at whether they can treat heart failure as well. Their heart-failure potential has yet to be established, mainly due to PH patients experiencing excess fluid retention and a worsened disease early in the treatment.
Actelion conducted the Phase 2 MELODY-1 trial (NCT02070991) to “generate more evidence about the potential benefit” of endothelin receptor antagonists “in patients with post- and pre-capillary PH,” the researchers wrote.
The team looked at whether Opsumit-treated patients gained a lot of weight due to fluid overload. The yardstick was at least 5 percent additional weight, or more than 5 kg.
Researchers also assessed whether Opsumit could prevent a worsening of PH stemming from a left heart disease.
The study covered 63 patients at 28 locations in 11 countries. Researchers randomized participants to receive either Opsumit or a placebo for 12 weeks.
Twenty-three percent of the 31 Opsumit-treated patients and 13 percent of the 32 controls experienced significant fluid retention or disease progression during the trial. The difference in fluid retention between the two groups showed up in the first month.
By the end of the treatment, Opsumit had failed to improve a number of patients’ lung and heart functions better than the placebo.
One measure was resistance to blood flow in the lungs, or pulmonary vascular resistance. Another was mean pressure in the right atrium of the heart. Still another was pulmonary arterial wedge pressure, which doctors measure by wedging a catheter with an inflated balloon into a small lung artery.
The heart function improvement that the Opsumit group achieved was so small that researchers deemed it insignificant. Patients’ improvement in levels of a heart activity biomaker known as NT-proBNP was also considered insignificant.
“The data remind us that, as of yet, we do not have an effective therapy for this patient population,” the researchers wrote.
In terms of safety, more Opsumit-treated than placebo patients experienced at least one serious adverse event and had to discontinue treatment early. Eight Opsumit patients and six controls experienced at least one adverse event stemming from fluid overload or edema — swelling due to fluid accumulation.
The researchers concluded that patients treated with Opsumit were “quantitatively more likely to experience significant fluid retention versus placebo” and that the drug had no significant impact on the patients’ heart function.