FDA Accepts Biologics License Application for Priority Review of Sotatercept in Treatment of Pulmonary Arterial Hypertension

The FDA has accepted a new biologics license application for sotatercept (Merck) for priority review as a treatment for adults with pulmonary arterial hypertension (PAH). The FDA has issued a Prescription Drug User Fee Act fate of March 26, 2024.¹

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Sotatercept is a novel investigational activin signaling inhibitor developed by Merck.

“The FDA’s acceptance of this application is an exciting milestone in our journey to bring this novel activin signaling inhibitor to patients. Based on the profound improvements across primary and secondary outcome measures in the phase 3 STELLAR trial, we believe sotatercept has the potential to transform the treatment of patients with PAH. We look forward to working closely with the FDA to bring sotatercept to patients in need,” Joerg Koglin, MD, PhD, senior vice president of global development at Merck Research Laboratories, said in a statement.¹

The application was based on data from the STELLAR trial (NCT04576988), which demonstrated a statistically significant and clinically meaningful improvement in 6-minute walk distance and 8 of 9 of the secondary outcomes for sotatercept.¹

The 9 secondary endpoints included multicomponent improvement, change in pulmonary vascular resistance, N-terminal pro-B-type natriuretic peptide level, improvement in WHO Functional Class, time to clinical worsening death, French risk score, and PAH-SYMPACT Physical Impacts, Cardiopulmonary Symptoms and Cognitive/Emotional Impacts domain scores.¹ The first 8 secondary endpoints were significantly improved with the investigational drug compared to the placebo.²

Individuals included in the study were adults with PAH who were being treated with background therapy with WHO Functional Class II or III.¹ A total of 163 individuals were assigned to receive sotatercept and 160 received the placebo.²

According to the results of the study, the median change from baseline at week 24 in the 6-minute walk distance was 34.4 meters for those receiving sotatercept and 1 meter for those receiving the placebo. The difference between both groups in the change from baseline at week 24 was 40.8 meters, investigators reported.²

Of those in the sotatercept group, 38.9% met all 3 criteria of the multicomponent improvement endpoint compared with 10.1% in the placebo group. Furthermore, all but 1 individual in the sotatercept group received the maximum dose of 0.7 mg/kg during the trial period. Approximately 89% had no dose reduction in the trial period and 6.1% had at least 1 dose reduction. Adherence was 98.4% in the sotatercept group and 99% in the placebo group.²

According to the study results, 84.7% experienced any adverse effects (AEs), with 41.1% being related to the drug. Three individuals discontinued the drug and withdrew from the trial due to AEs.²

AEs of special interest included thrombocytopenia, bleeding events, increased blood pressure, and telangiectasia. AEs reported in 10% or more of either group included headache, COVID-19, nausea, diarrhea, fatigue, epistaxis, telangiectasia, and dizziness, according to the study investigators.²

The results were published in The New England Journal of Medicine and presented at the American College of Cardiology’s 72nd Annual Scientific Session with the World Heart Federations World Congress of Cardiology.¹

References

1. Merck receives priority review from FDA for new biologics license application for sotatercept, an activin signaling inhibitor to treat adults with pulmonary arterial hypertension (PAH). News release. Merck. September 28, 2023. Accessed September 28, 2023. https://www.merck.com/news/merck-receives-priority-review-from-fda-for-new-biologics-license-application-for-sotatercept-an-activin-signaling-inhibitor-to-treat-adults-with-pulmonary-arterial-hypertension-pah/
2. Antrim A. Sotatercept improves exercise capacity in individuals with pulmonary arterial hypertension. Pharmacy Times. April 27, 2023. Accessed September 28, 2023. https://www.pharmacytimes.com/view/sotatercept-improves-exercise-capacity-in-individuals-with-pulmonary-arterial-hypertension