FDA Approves Potential ‘Game Changer’ for Pulmonary Arterial Hypertension

Merck Research Laboratories_iStock, Michael Vi

Pictured: Merck Research Laboratories in California/iStock, Michael Vi

Merck’s $11.5 billion acquisition of Acceleron Pharma paid dividends Tuesday as the FDA approved sotatercept, the cornerstone of the deal, to treat pulmonary arterial hypertension.

The drug, which will carry the brand name Winrevair, is the first FDA-approved activin signaling inhibitor therapy for PAH, according to Merck’s announcement. This new therapeutic class improves the balance between pro- and anti-proliferative signaling to regulate vascular cell proliferation, an underlying cause of PAH. 

Winrevair is intended to be used alongside existing PAH therapies to increase exercise capacity, lessen the severity of PAH and reduce the risk of disease worsening.

Merck has priced Winrevair at $14,000 per vial before insurance, according to multiple sources.

The drug came into Merck’s possession with the 2021 acquisition of Acceleron. “[Winrevair] was the main opportunity that we saw with the Acceleron acquisition,” Mahesh Patel, VP of global clinical development at Merck Research Laboratories, told BioSpace. “We have been so fortunate in how well things have gone in the acquisition, executing on the clinical development program and seeing paradigm-changing clinical trial results through it.”

In October 2022, Winrevair hit the primary Phase III endpoint, eliciting a statistically significant and clinically meaningful improvement in the 6-minute walk distance test after 24 weeks. The drug also reached statistical significance in secondary endpoints, including time to patient death or the first occurrence of a clinical worsening event. 

Patel said that before Winrevair, treatments for PAH had only dilated the arteries, opening blocked or narrowed blood vessels and allowing more oxygen to flow. However, earlier medicines have not addressed the root causes of the disease. Winrevair has the chance to “dramatically change” patients’ physical function and quality of life, Patel said.

Tuesday’s approval follows that of Johnson & Johnson’s Opsynvi, a single-tablet combination of macitentan and tadalafil, which received the FDA’s green light on March 22 for adults with PAH.

But Jeremy Feldman, director of the pulmonary hypertension program and medical director for high-risk care at Summit Heath, who was also involved in Winrevair’s Phase II and III trials, expressed more excitement about this medicine.

“Without a doubt, sotatercept is a game changer,” he told BioSpace. “I think the way that that will impact patients is very different than the availability of a combo tablet that doesn’t advance the care of patients. It may advance the convenience of patients a little bit.” He added that Winrevair is a particularly effective agent on top of the approved therapies and is particularly well-tolerated in terms of day-to-day side effects. “I think there’s a question mark that still has not been fully answered about the long-term safety of the medication, but that’s not an unfamiliar space for us to be in with a disease process that has still a very high mortality.”

Winrevair's label lists warnings for erythrocytosis, which may increase the risk of thromboembolic events and hyperviscosity syndrome, and severe thrombocytopenia, which may increase the risk of bleeding. 

An Expanding Market

Winrevair and Opsynvi enter a growing PAH market, which Prophecy Market Insights projects will be worth $12.2 billion by 2032. An increasing geriatric population married with global increases in chronic diseases has led to a rise in the need for PAH medicines, according to the report. As of December 2023, approximately 129 drugs were in development for PAH by 110 companies, institutes and universities, Pharmaceutical Technology reported.

Patel said Merck plans to investigate Winrevair for other unmet needs in PAH, including on trial its potential use within one year of diagnosis and a second trial in patients who potentially are at very high risk for progressive morbidity and mortality.

Tim Noyes, CEO of Aerovate Therapeutics, which is also developing a PAH candidate, said this is an “exciting” time to be in the space. For the past 20 years, the “bedrock” of care has been using dilators, or vasodilators, Noyes told BioSpace. While this has made a difference for patients, the underlying problem with PAH is cell proliferation with arteries narrowing from the inside out, he said.

“To get to that next level, to allow patients to really start to have an agent that addresses the underlying cause of their disease, it’s anti-proliferative agents and [that’s] why there’s so much enthusiasm for sotatercept,” Noyes said.

Aerovate’s candidate, a tyrosine kinase inhibitor, is a dry-powder aerosol version of Novartis’ cancer drug Gleevec. Noyes sees the drug as complementary to Winrevair as opposed to being necessarily a competitor. “Each has its . . . specific benefits to patients, entirely different mechanisms,” he explained.

Winrevair will be available to patients at select pharmacies at the end of April, according to Merck’s announcement.

“A diagnosis of PAH is a life-changing experience for patients and families due to its chronic, progressive nature. Patients with PAH experience limiting symptoms such as shortness of breath and fatigue,” Matt Granato, president and CEO of the Pulmonary Hypertension Association, said in a statement. “We are excited to see industry research leading to a better understanding of PAH and the development of a medicine in a novel treatment pathway that expands options for the patient community.”

Tyler Patchen is a staff writer at BioSpace. You can reach him at tyler.patchen@biospace.com. Follow him on LinkedIn.

Correction (March 27): This story has been updated from its original version to reflect that Aerovate does believe that its candidate, if approved, could be used in combination with Winrevair. BioSpace regrets the error. 

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