Sotatercept, the newest drug approved to treat pulmonary arterial hypertension (PAH) has been on the market Since May of 2024. In the phase 2 PULSAR trial and phase 3 STELLAR trial, sotatercept delivered impressive results, lowering pulmonary artery pressures, improving exercise capacity and leading to improvement in risk status and improved right heart function.
Merck recently delivered another home run with sotatercept when they published the results of the ZENITH Trial. This trial included patients with very advanced PAH. The trial was stopped early when it became clear that the drug was powerfully effective: reducing the risk of worsening by 75%, and reducing the risk of death by almost 50%.
The ZENITH trial did not uncover any new safety issues. The most common side effects were nose bleeding and the development of small new blood vessels on the skin that appear as red dots. These side effects had been seen in earlier trials as well and infrequently led to patients having to stop the medication.
With the remarkable efficacy in patients with PAH demonstrated in both advanced disease and less advanced disease, Merck decided to stop the HYPERION trial. This trial was evaluating sotatercept in recently diagnosed PAH patients. Although the scientific community would have welcomed even more data to guide doctors as to how best to use sotatercept, it was no longer ethically appropriate to randomize patients with PAH to a prolonged period of time on placebo rather than sotatercept.
We anticipate that Merck will report on the results of the incomplete HYPERION study. These results will have to be interpreted in the context of the trial’s early termination. Regardless of the results of HYPERION, it is now clear that sotatercept has earned a very important role in the treatment of PAH.
