Is sotatercept, which traps activins and growth differentiation factors, a new dawn in treating pulmonary arterial hypertension (PAH)?

ABSTRACT

Introduction

Although the prevalence of pulmonary arterial hypertension (PAH) is low, mortality is high. In PAH, there is a down-regulation of the bone morphogenetic protein receptor type 2 pathway, leading to a prominence of the upregulation pathway that is mediated by activins and growth differentiation factors acting at the receptor type IIA (ActRIIA). Sotatercept is an ActRIIA fusion protein. STELLAR was a phase 3 study of sotatercept for the treatment of PAH.

Areas covered

STELLAR. The primary endpoint of STELLAR was change from baseline at 24 weeks in the 6-minute walking distance, which was increased by 34.4 m by sotatercept compared to 1 m in the placebo group. Epistaxis/nosebleed, telangiectasia, and dizziness were more common with sotatercept than placebo.

Expert opinion

By targeting the remodeling in PAH, sotatercept is providing a new approach to the treatment of PAH and has the potential to slow or reverse cardiovascular remodeling in other conditions, e.g. left heart failure. However, the development of sotatercept for the treatment of PAH still requires a consideration of the appropriate dose and a longer-term assessment of the benefits and safety. If sotatercept becomes available for self-administration, it will be of interest to assess whether this affects adherence and benefits.

KEYWORDS:

• Activin
• bone morphogenetic protein receptor type 2
• clinical trial
• pulmonary arterial hypertension
• sotatercept

Declaration of Interest

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.