SPECTRA Phase 2b Study: Impact of Sotatercept on Exercise Tolerance and Right Ventricular Function in Pulmonary Arterial Hypertension.

Background: This study aims to assess the impact of sotatercept on exercise tolerance, exercise capacity, and right ventricular function in pulmonary arterial hypertension.
Methods: SPECTRA (Sotatercept Phase 2 Exploratory Clinical Trial in PAH) was a phase 2a, single-arm, open-label, multicenter exploratory study that evaluated the effects of sotatercept by invasive cardiopulmonary exercise testing in participants with pulmonary arterial hypertension and World Health Organization functional class III on combination background therapy. The primary end point was the change in peak oxygen uptake from baseline to week 24. Cardiac magnetic resonance imaging was performed to assess right ventricular function.
Results: Among the 21 participants completing 24 weeks of treatment, there was a significant improvement from baseline in peak oxygen uptake, with a mean change of 102.74 mL/min ([95% CIs, 27.72-177.76]; P =0.0097). Sotatercept demonstrated improvements in secondary end points, including resting and peak exercise hemodynamics, and 6-minute walk distance versus baseline measures. Cardiac magnetic resonance imaging showed improvements from baseline at week 24 in right ventricular function.
Conclusions: The clinical efficacy and safety of sotatercept demonstrated in the SPECTRA study emphasize the potential of this therapy as a new treatment option for patients with pulmonary arterial hypertension. Improvements in right ventricular structure and function underscore the potential for sotatercept as a disease-modifying agent with reverse-remodeling capabilities.
Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03738150.
Competing Interests: Disclosures Dr Waxman is a Steering Committee member for Acceleron Pharma, a wholly owned subsidiary of Merck & Co Inc (Rahway, NJ) and United Therapeutics; and is an investigator and principal investigator for Acceleron Pharma, Aria CV, OrphAI, and United Therapeutics. Dr Manimaran is an employee of Acceleron Pharma. Dr de Oliveira Pena is an employee of Oorja Bio Inc and a former employee of Acceleron Pharma. Dr Lu is an employee of SalioGen Therapeutics and a former employee of Acceleron Pharma. F. P. Rischard has been a consultant for Acceleron Pharma and United Therapeutics. He has received research support from Acceleron Pharma, Bayer, ISMed, Janssen, the National Heart, Lung, and Blood Institute, the National Institutes of Health, and United Therapeutics. The other author reports no conflicts.