At ACC 2023, Hoeper provides insight into the key efficacy findings of STELLAR and delves into the safety concerns and generalizability of sotatercept for PAH.
The addition of sotatercept to optimal background therapy was associated with a statistically significant improvement in 6-minute walk distance in adults with pulmonary arterial hypertension (PAH), according to the phase 3 STELLAR trial results.1
At the American College of Cardiology (ACC) 2023 Annual Scientific Session, HCPLive spoke with presenting investigator Marius M. Hoeper, MD, Hannover Medical School, and broke down some of the most relevant findings from the STELLAR program.
Hoeper noted the approximately 40-meter improvement in the 6-minute walk distance with sotatercept was due to improvement in those patients, rather than the deterioration of the placebo-treated patients.
He discussed the safety data, as signals including increased hemoglobin levels, telangiectasia, and epistaxis were observed more frequently among the sotatercept arm than among the placebo arm. Hoeper noted that these signals have not been alarming yet, but clinicians need to remain vigilant.
We expect that patients are going to be exposed to this drug for many years,” he said. “And of course, we need to be cautious and vigilant to make sure that this doesn’t develop into something more serious than what we see now.”
STELLAR data showed the risk of death or nonfatal clinical worsening events, assessed up to the end of the trial, was 84% lower with sotatercept than with placebo. However, the trial was not designed or powered to study the effects on morality. Hoeper noted the risk reduction was in a composite endpoint of a non-fatal clinical worsening event or death.
“We shouldn’t make a claim for the time being that this drug is going to affect mortality, “Hoeper said. “It will. My personal opinion is it would definitely and clearly show patients live longer with this drug. But, formally, this has not been demonstrated with this study.”
Hoeper additionally spoke to the generalizability of the STELLAR results, particularly for a real-world population or those who may not be clinically stable or have been on background therapy. He lastly spoke to the ideal indication for sotatercept, given the therapy’s Breakthrough Therapy designation the U.S. Food and Drug Administration
Hoepe noted the ideal indication is what has been studied, with classical PAH. This includes the idiopathic, heritable, and the connective tissue disease-associated forms.
“We definitely need more data on congenital heart disease, which is a big group and the study included patients with corrected congential heart disease, but there’s so much more,” Hoeper said. “Of course, there’s also some concerns especially with patients with uncorrected disease and Eisenmenger syndrome, they often have higher hemoglobin levels to start with. There is concern to give a drug that increases hemoglobin even further, but all of this is definitely something that needs to be studied in the future.”
1. Hoeper MM, Badesch DB, Ghofrani HA, et al. Phase 3 Trial of Sotatercept for Treatment of Pulmonary Arterial Hypertension. New England Journal of Medicine. March 2023. Doi: 10.1056/NEJMoa2213558
2. Adding sotatercept to existing therapy shows promise in treating rare heart-lung condition. American College of Cardiology. https://www.acc.org/About-ACC/Press-Releases/2023/03/06/14/02/Adding-Sotatercept-to-Existing-Therapy-Shows-Promise.