ZENITH: Novel Biologic Reduces Morbidity and Mortality in PAH

In patients with advanced pulmonary arterial hypertension (PAH), the addition of the biologic sotatercept-csrk (Winrevair; Merck) to maximum tolerated background therapy reduces the risk of death more than background therapy alone, according to top-line results of the ZENITH trial.

In an announcement yesterday the study sponsor, Merck, said that an interim analysis had revealed that ZENITH had met its primary endpoint of time to first morbidity or mortality event. In response, the trial’s independent data monitoring committee recommended that the phase III trial be terminated early to allow all study participants to enter into an open-label extension study and receive the drug.

As TCTMD previously reported, the injectable activin signaling inhibitor was the first drug in this class to be approved by the US Food and Drug Administration in March. The biologic agent enhances the balance between pro- and antiproliferative signaling to modulate vascular proliferation. The approval was based on data from the STELLAR trial, which showed that patients on sotatercept-csrk had greater improvement in exercise capacity as evidenced by longer 6-minute walk times over 24 weeks compared with those on placebo. There also were reductions in the incidence of death and nonfatal clinical worsening of PAH.

ZENITH enrolled 172 patients with PAH (WHO functional class III or IV). Morbidity and mortality events were defined as all-cause death, lung transplantation, or PAH worsening-related hospitalization of ≥ 24 hours. Secondary outcome measures included overall survival, transplant-free survival, and several additional measures. Adverse events and serious adverse events were similar in the treatment and placebo groups.

According to Merck, the full ZENITH results will be presented at an upcoming medical meeting and will be submitted to regulatory authorities. Sotatercept-csrk is available in 36 other countries outside of the US and has been submitted to Japanese regulatory authorities for approval based on both the STELLAR results and an open-label study in Japanese patients.