Merck’s pulmonary arterial hypertension drug Winrevair cut the risk of “clinical worsening” — an endpoint made up of a variety of signs showing that a patient’s illness is progressing — by 76% in recently diagnosed patients.
It’s an eye-opening statistic, but also comparable to
previous trials
.
The difference is that Merck’s previous studies on Winrevair, also known as sotatercept, included patients with more advanced disease or those who had been diagnosed with PAH several years earlier. The latest study, a Phase 3 trial called HYPERION, instead assessed adding Winrevair on top of standard background treatments within the first year of diagnosis.
The data were
reported
Tuesday at the annual European Respiratory Society meeting and published in the
New England Journal of Medicine
.
With these data in hand, Merck hopes to convince prescribers to give its drug earlier. Winrevair, one of Merck’s biggest new drug launches, is expected to become a multibillion-dollar product. In the first half of this year, Winrevair generated $616 million in sales.
The drug is currently approved to treat adults with PAH, which occurs when blood pressure in the arteries that carries blood from the heart to lungs is abnormally high. PAH can lead to shortness of breath, fatigue and chest pains, among other symptoms. Winrevair is meant to lower that blood pressure by blocking a protein known as activin in hopes of preventing those blood vessels from thickening.
Merck is also awaiting Phase 2 results for the drug in certain patients with heart failure. That study will signal whether Merck could further expand the use case for Winrevair. The study likely completed this month, according to the
federal clinical trials database
, and is expected to read out this year. Merck declined to comment on the timing of the data.
Though Merck’s past studies looked at Winrevair in patients later in the course of their disease, the FDA granted the drug a broad label in PAH. But the “clinical reality” was that Winrevair was primarily used in patients who had been diagnosed for a long time, akin to the patient populations of its earlier studies, according to Joerg Koglin, Merck’s head of general and specialty medicine.
Those patients were likely on three background therapies for PAH before Winrevair, he told
Endpoints News
, whereas the majority of patients in the recently diagnosed study were on two.
The primary endpoint of the study — “clinical worsening” — included events such as deterioration in performance on an exercise test, hospitalization or death.
With a median follow-up of 13 months, 10.6% of patients in the sotatercept group experienced one of those events, while 36.9% in the placebo group did. That difference resulted in a hazard ratio of 0.24 and a P<0.001. Deterioration in performance on an exercise test accounted for a substantial proportion of those events; eight patients, or 5%, of the sotatercept group saw that happen, compared to 46 patients, or 28.8%, of the placebo group.
“I believe the data will point physicians to the idea [that] if this is something that treats the underlying root cause of the disease, perhaps it makes sense to consider initiation of sotatercept earlier in an individual patient’s disease journey rather than later,” Koglin said.
Koglin also pointed out that the difference between the Winrevair group and placebo arm became apparent within a few doses.
Merck notably stopped this study early after a previous study (which was also stopped early) showed Winrevair cut the risk of death, lung transplantation and hospitalization. As a result, the program’s steering committee said it was no longer ethical to continue enrolling patients in a trial comparing Winrevair to placebo. Merck is also waiting for a label update by Oct. 25 to add the new information about reduced risk of death and other major events.
The company also plans to submit the HYPERION results to the FDA.
The HYPERION study enrolled 320 patients, divided into the two groups who got background therapies and then either sotatercept or placebo. Background therapies typically included a combination of endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and prostacyclin analogues.
The side effects of Winrevair looked similar to past studies, with 31.9% of patients on Winrevair experiencing a nosebleed, the most common side effect in the trial.
Editor’s note: This story was updated to add that Merck plans to submit the HYPERION results to the FDA.