Sotatercept Added to PAH Therapy Improves Exercise Ability in Patients
With STELLAR trial data, Merck plans to apply for regulatory approval
Treatment with sotatercept, given in addition to standard therapies, significantly improves exercise capacity in people with pulmonary arterial hypertension (PAH).
Those are the new findings of a pivotal Phase 3 clinical trial called STELLAR, which tested the therapy’s safety and efficacy in improving PAH patients’ ability to walk.
Now, the company developing sotatercept, Merck — known as MSD outside the U.S. and Canada — is planning to apply for regulatory approvals based on these results. Merck acquired Acceleron Pharma, sotatercept’s previous developer, in a deal last year worth $11.5 billion.
“We believe that in totality, the results observed in the STELLAR study suggest that sotatercept has the potential to transform the treatment of patients with PAH. We are moving with urgency on our regulatory applications to bring this investigational therapy to these patients,” Dean Li, MD, PhD, president of Merck Research Laboratories, said in a press release.
The STELLAR trial (NCT04576988), sponsored by Acceleron, enrolled 324 adults with PAH. Participants were randomly assigned to take sotatercept or a placebo, administered via subcutaneous injection (under the skin) every three weeks, on top of their standard-of-care PAH therapies.
The trial was double-blind, meaning that neither the participants nor researchers knew which patients were receiving the medication and which the placebo.
The dose for those given sotatercept started at 0.3 mg/kg, and was increased up to 0.7 mg/kg based on tolerability.
Top-line results
The main goal of the trial was to assess the effect of treatment on six-minute walk distance (6MWD) after 24 weeks, or about six months. 6MWD, which simply measures the distance a person can walk in six minutes, is commonly used as a measure of exercise capacity in people who are able to walk.
According to Merck, top-line results from the study show that sotatercept treatment led to “statistically significant and clinically meaningful improvement” in 6MWD. The company did not disclose the magnitude of the change, noting full results will be presented at a future scientific conference.
“In the Phase 3 STELLAR study, sotatercept added to currently approved background therapy showed a profound effect on the primary efficacy outcome measure of improvement from baseline to 24 weeks in six-minute walk distance,” Li said.
Statistically significant improvements also were seen in eight of nine secondary efficacy endpoints or goals. These included the number of patients achieving multicomponent improvement — a composite measure that includes 6MWD alongside assessments of functional class and a biomarker of heart health called NT-proBNP.
The time to clinical worsening or death was significantly longer in patients on sotatercept, according to Merck.
The only secondary endpoint in which significant improvements were not detected was the Cognitive/Emotional Impacts domain score of a measure of disease impact called the PAH-SYMPACT.
“The results from the secondary efficacy outcomes, including a favorable benefit seen in patients’ time to a clinical-worsening event, are especially noteworthy,” Li said.
Sotatercept is designed to rebalance the biochemical pathways that drive abnormal blood vessel growth in PAH by trapping certain signaling molecules. The experimental treatment has been granted orphan drug designation in the U.S. and in Europe; it also received priority medicines (PRIME) designation in the EU and breakthrough therapy status in the U.S.
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