Sotatercept Improves Vascular Resistance In Pulmonary Arterial Hypertension In Early Trial

Subcutaneous injections of the experimental drug sotatercept, given every 21 days, can reduce pulmonary vascular resistance by 34% in people with pulmonary arterial hypertension (PAH), according to the results of a phase-2 trial.

Volunteers who received a lower dose of the drug saw resistance drop by 21% over 24 weeks among people whose small pulmonary arteries had been constricted by the rare and chronic disorder. The decline was just 2.1% with placebo, researchers report in the New England Journal of Medicine.

And while placebo therapy increased six-minute walk distance by 29 meters as calculated by the least-squares mean method, it rose 58 meters with lower-dose sotatercept and 50 meters with the higher dose, compared to baseline.

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PAH elevates pulmonary blood pressure and strains the heart to the point where the five-year survival is about 57%. The condition can progress rapidly.

"This is a propitious advance for this difficult and fatal disease," writes Dr. John Newman of Vanderbilt University Medical Center in Nashville, Tennessee, in an accompanying editorial. "The results of the trial justify the need for longer trials and inclusion of sicker patients" for evaluating the fusion protein therapy.

The new study, known as PULSAR, looked at 106 patients treated at 43 centers in eight countries who continued to receive conventional therapy. It did not look at mortality or other clinical outcomes.

Seventy percent had idiopathic or heritable disease. The condition was associated with connective-tissue disease in 20%.

At the lower dose, the least-squares mean difference in pulmonary vascular resistance after 24 weeks was significant with P=0.003 compared with placebo. At the higher dose the significance was P<0.001.

When all the sotatercept patients were considered, 23% had improved clinical functioning.

Dr. Newman characterized the extra distance that sotatercept recipients walked as "weak improvement."

"Future studies involving sicker patients are warranted to evaluate the broad efficacy of the drug," he said.

One of the 42 patients in the high-dose group died of cardiac arrest. The most common hematologic side effects in the study were thrombocytopenia, seen in 12% of patients in the high-dose group, and increased hemoglobin levels, seen in 17% of that cohort.

The rates of serious adverse events were 9% with placebo, 6% in the low-dose group and 12% in the high-dose arm.

"All the events were reversible after delay, reduction, or discontinuation of sotatercept or placebo," the research team, led by Dr. Marc Humbert of Bicetre Hospital in Le Kremlin-Bicetre, France, writes.

PULSAR was financed, designed, conducted and monitored by Acceleron Pharma. The company also performed all the data analysis.

An 18-month active-drug extension study is ongoing.

—Reuters Staff

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