Key takeaways:

The FDA based sotatercept’s/Winrevair’s approval on data from the phase 3 STELLAR trial.
Additional studies on Winrevair are being conducted in different pulmonary arterial hypertension patient groups.

The FDA has approved sotatercept, an activin signaling inhibitor, for treating adults with pulmonary arterial hypertension, according to a manufacturer-issued press release.

In September 2023, the FDA granted priority review to sotatercept (Winrevair, Merck).

“What’s so exciting to us about sotatercept is that it actually has the potential to impact the disease at a fundamental level,” Mahesh Patel, MD, vice president of global clinical development at Merck research laboratories in the cardiovascular and respiratory therapeutic area, told Healio. “It addresses the root problem with the thickening of the pulmonary arterial blood vessel walls, and in doing so, it treats the disease more directly and leads to really profound benefits to patients.”

This approval comes only a few days after the approval of Opsynvi (Johnson & Johnson), a once-daily tablet that includes two previously approved drugs (macitentan and tadalafil), also designated to treat adults with PAH.

The FDA based its decision on Winrevair, in part, on data from the phase 3, randomized, double-blind, placebo-controlled STELLAR trial, which found that Winrevair plus background therapy improved 6-minute walk distance by 40.1 m (95% CI, 29.9-50.2) between baseline and week 24 of treatment vs. a decline of –1.4 m (95% CI, –13.2 to 10.3; P < .001) in the placebo group.

Trial data published in The New England Journal of Medicine and presented at the 2023 American College of Cardiology Scientific Session also showed that the Winrevair group had a lower risk for death and clinical worsening by 84%.

Further, patients receiving Winrevair outperformed patients receiving placebo in eight out of nine assessed secondary endpoints, according to a previous press release and study results.

“Sotatercept will be administered every 3 weeks, and the use of the drug will be overseen by a health care professional,” Patel said. “But, over time per their guidance and discretion … a patient or one of their caregivers could administer the drug.”

Prior to this approval, an Institute for Clinical Economic Review (ICER) report suggested that Winrevair plus background therapy would exceed typical cost-effectiveness thresholds.

“We did not take into account ICER’s model while pricing Winrevair, as we believe it does not account for the full value and impact of Winrevair on patients living with PAH,” a Merck spokesperson told Healio. “We’ve publicly shared numerous areas where we feel ICER’s approach does not appropriately reflect the experience of patients with PAH or the value of Winrevair.”

Patel added that the value of the drug has been made clear by patients and physicians.

“I think it’s quite clear based on how receptive patients and physicians have been to the clinical trials in their participation that they view this as very valuable,” he said. “The benefit-risk profile overall has been strong enough that patients continue on in our long-term extension studies, such as SOTERIA.”

When asked about future studies on Winrevair, Patel highlighted two phase 3 studies — HYPERION and ZENITH — that are evaluating the drug in different PAH disease trajectories.

“With HYPERION, we’ll be looking at patients that are earlier in their disease journey, within 1 year of diagnosis,” Patel said. “We’ll have, through that study, a better understanding of what impact the drug has on improving outcomes in patients when started earlier.

“ZENITH evaluates higher risk patients, functional class three and four patients, and is looking at hard outcomes such as hospitalizations, transplantation and death in these patients,” Patel continued.

Patel also noted a phase 2 study (CADENCE) that is being conducted to assess the drug in patients with a form of PH related to heart failure with preserved ejection fraction.

“That study will help us understand if sotatercept can have even a broader effect on different types of PH,” Patel said.