Winrevair Gains EU Nod, Expanding PAH Options

Merck & Co.’s new pulmonary arterial hypertension (PAH) has scored a major new approval, even as clinicians begin to rethink how the novel therapy will fit into the treatment strategies.

Late last month, the European Commission approved Winrevair (sotatercept) for sale in the 27 member states of the European Union, as well as Iceland, Liechtenstein, and Norway. The therapy was approved for use in combination with other PAH therapies in adult patients with functional class II-III disease. Merck noted that the approval makes the therapy the first (and only) approved PAH therapy that targets the activin signaling pathway.

"We are proud to bring this innovative treatment to more patients and remain committed to further investigating the potential of Winrevair in areas where there are unmet need in the management of PAH, said Joerg Koglin, M.D., Ph.D., the company’s head of general medicine, global clinical development, in a news release.

The European approval came five months after the FDA approved the therapy.

In the phase 3 STELLAR trial, 163 patients were treated with sotatercept in combination with standard-of-care background therapies. Compared to a 160-patient placebo group, those receiving sotatercept had significant improvement in six-minute walking distance (6MWD), along with a lower risk of death and clinical worsening.

“These findings are significant and reinforce that Winrevair, in combination with other PAH therapies, should be considered as a new standard of care for the treatment of functional class II and III adult patients,” said Marc Humbert, M.D, PhD, of the Paris-Saclay University, in the press release.

But how exactly Winrevair will fit into current clinical practice remains to be seen. Tyler Pitre, M.D., Ph.D., of the University of Toronto, noted that current international guidelines typically call for dual therapy at first in most patients being treated for PAH. That usually means pairing a phosphodiesterase 5 inhibitor (PDE5i) with an endothelin receptor agonist (ERA). However, he also noted that some patients take additional therapies.

“In both the STELLAR and PULSAR trials, approximately 60% of the participants were already on triple therapy, meaning a combination of ERA plus PDE5i, plus another agent which is typically oral prostanoid therapy,” he said. “Some of the patients in these trials were on continuous epoprostenol therapy as well.” PULSAR was a phase 2 trial of Winrevair.

In a meta-analysis recently published in the Annals of the American Thoracic Society, Pitre and colleagues analyzed studies to compare Winrevair with other approved add-on therapies for PAH. Their analysis concluded with moderate certainty that Winrevair likely reduces the risk of clinical worsening compared with add-on ERAs, inhaled prostanoids, and oral prostanoids. They also found — again with moderate certainty — that the therapy improves 6-minute walk distance compared to ERAs and oral prostanoids, though they said the improvement in those cases did not meet the level of clinically important improvement.

Asked if any findings surprised him, Pitre said he was pleased with the breadth of the new drug's efficacy. “As for a surprise,” he said, “I was interested to see how stably effective sotatercept was throughout comparisons and also across outcomes.”

Pitre noted that in Canada, where he lives, the Winrevair is not yet readily available. That is likely to change soon, though. Canadian regulators OKed the drug on Sept.4, and it is now approved for use in adults in combination with standard PAH therapies.

Pitre observed that, in his and his colleagues’ meta-analysis, Winrevair was effective even when compared to dual therapy, “so there is some evidence to suggest Winrevair could be used up front as well.”

However, he also cautioned that the high-cost medication may be subject to prescribing limitations in certain jurisdictions. In Canada, Pitresaid, “I suspect they will require that patients be on at least dual or even triple therapy before we can prescribe it,” he said.