Merck’s Sotatercept Shows Stellar Performance in Phase III

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Top-line data from the Phase III STELLAR trial revealed that Merck’s activin receptor candidate sotatercept reached its primary endpoint in pulmonary arterial hypertension (PAH), the company announced Monday.

Patients treated with sotatercept saw a statistically significant and clinically meaningful increase in 6-minute walk distance (6MWD) at the 24-week follow-up. Merck’s PAH hopeful also elicited multicomponent improvement, a composite endpoint comprising 6MWD, N-terminal pro-B-type natriuretic peptide levels and functional class.

Sotatercept also met almost all of STELLAR’s secondary endpoints, including a longer time to patient death or the first occurrence of a clinical worsening event.

The only metric that sotatercept failed to improve upon was the score in the Cognitive/Emotional impacts domain of the PAH-SYMPACT questionnaire, a disease-specific tool used to assess the symptoms and impacts of PAH.

Dean Li, president of Merck Research Laboratories, said in a statement that STELLAR’s primary and secondary efficacy findings underline the potential of sotatercept “to transform the treatment of patients with PAH.” The company is working on sotatercept’s regulatory applications.

Enrolling more than 320 adult PAH patients, STELLAR is a randomized, double-blinded and parallel-group trial that compared sotatercept against placebo as an add-on to background therapy. Aside from efficacy, STELLAR also evaluated sotatercept’s safety and found that it had a tolerability profile consistent with Phase II findings. STELLAR’s results will also be presented at an upcoming scientific conference.

The $11B Gambit Pays Off

Sotatercept is a first-in-class compound composed of the extracellular domain of the activin receptor type IIA fused to the Fc domain of IgG1. Merck’s candidate works by restoring the balance between the pro-proliferative and anti-proliferative signaling pathways in the pulmonary arterial wall and right ventricular remodeling, both central to PAH pathology. The FDA granted sotatercept the Orphan Drug Designation in 2019.

Sotatercept was first discovered and developed by the rare disease biotech Acceleron Pharma. In September last year, rumors started circulating that Merck was looking to acquire Acceleron at around $180 per share.

After a slight delay due to objections from Acceleron’s stakeholders, the Big Pharma finalized the deal two months later, in November, eventually dropping $11.5 billion to complete the buyout—and ultimately besting other bidders for Acceleron, including fellow giant Bristol Myers Squibb.

The buyout gave Merck the rights to sotatercept, boosting its own existing PAH pipeline, which includes Adempas (riociguat), a compound that stimulates the soluble guanylate cyclase (sGC) and was first approved by the FDA for PAH in 2013. Merck won Adempas in a licensing agreement with Bayer. Merck also owns MK-5475, an inhalable sGC stimulator that is currently being assessed in a Phase II/III trial in PAH.

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