MSD adds rocket fuel to Winrevair's engine in PAH

MSD's pulmonary arterial hypertension (PAH) drug Winrevair has been accelerating at a breakneck pace since its launch earlier this year – and data from a new phase 3 study could give it a turbo boost.

Winrevair (sotatercept) was able to extend the time to the first morbidity or mortality event – all-cause death, lung transplantation, or hospitalisation due to worsening PAH for at least 24 hours – compared to placebo when given on top of background PAH therapy in the ZENITH trial.

The "overwhelming efficacy" seen with the activin signalling inhibitor in the study has led the investigators to stop it early, allowing all patients to receive Winrevair as part of an open-label extension study called SOTERIA, said MSD.

In March, Winrevair became the first FDA-approved therapy for PAH that addresses the underlying mechanism behind the disease, rather than its symptoms, and has also been cleared in Europe and filed in Japan based on the results of the STELLAR trial.

It has seen rapid take-up since launch, with third-quarter sales reaching $149 million - well ahead of expectations and putting the drug on course to meet MSD's sales projections of more than $3 billion a year at peak.

The company – known as Merck & Co in the US and Canada – acquired sotatercept as part of its $11.5 billion takeover of Acceleron Pharma in 2021, a deal which also gave it Reblozyl (luspatercept) for anaemia associated with rare blood disorders.

STELLAR showed that patients treated with sotatercept given on top of standard PAH therapy had an 84% lower risk of death or worsening of their condition compared with those on standard therapy alone, and its impact on survival is viewed as a major advance in treatment.

PAH is a life-threatening disease, caused by the narrowing of blood vessels in the lungs, and has a five-year survival rate of a little over 40%. Prior to Winrevair's launch, drug treatment was aimed at alleviating symptoms with agents that dilate blood vessels or increase blood flow through the lungs.

While the ZENITH data hasn't been revealed yet, the top-line result suggests it will reinforce the benefits seen in STELLAR, which could build further confidence among prescribers.

"These findings are impressive, set a high evidentiary bar for studies of future candidates developed for the treatment of PAH and support the potential of Winrevair to be practice-changing in the management of PAH," commented Dr Eliav Barr, chief medical officer at Merck Research Laboratories.

Meanwhile, MSD is running the phase 3 HYPERION trial of sotatercept in newly diagnosed intermediate- and high-risk PAH patients, seeking to move it up the treatment pathway, as well as the phase 2 CADENCE study in pulmonary hypertension associated with heart failure with preserved ejection fraction (HFpEF).

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