Merck scores key FDA approval for pulmonary arterial hypertension drug Winrevair

After three years, the crown jewel of Merck’s $11.5 billion acquisition of Acceleron is ready to pay dividends. With the FDA’s approval of Winrevair (sotatercept) to treat pulmonary arterial hypertension (PAH), Merck is set to launch the first disease-modifying treatment for the condition.

Initially developed by Acceleron and Celgene and investigated as a treatment for disorders such as osteoporosis, anemia and multiple myeloma, sotatercept has found its place as an add-on therapy to standard of care in a small but important indication.

PAH is a rare, rapidly progressing disease in which the blood vessels narrow in the lungs, increasing blood pressure and leading to heart failure. Roughly 40,000 people in the United States have the disorder. PAH strikes more women than men and most are in middle age, killing nearly half within five years of diagnosis. The condition begins as a more common disorder, pulmonary hypertension (PH), then can progress into PAH.

Merck will charge $14,000 for a vial of Winrevair, which is dosed subcutaneously every three weeks, putting its annual cost at $238,000. Based on the label-recommended, weight-based target dose and data gathered from the STELLAR trial, Merck projects that roughly two-thirds of patients will use a single-vial kit with others needed a double-vial package.

Two months ago, the Institute for Clinical and Economic Review (ICER) calculated a price range which matches the benefit patients are expected to receive for sotatercept at between $17,900 and $35,400 per year.

"We believe the U.S. price of Winrevair represents the significant innovation this medicine can deliver as a first-in-class activin signaling inhibitor therapy and the first biologic approved by the FDA for PAH," Merck said in a statement.  

Johnson & Johnson dominates the PAH market with Uptravi, a prostacyclin receptor (IP) agonist which generated sales of $1.6 billion last year on a 20% increase, and Opsumit, an endothelin receptor agonist which produced $2 billion in revenue, with its sales up 14% from 2022.

Additionally, just four days ago, the FDA approved a combination tablet Opsynvi, which combines Opsumit an United Therapeutics’ Adcirca (tadalafil), which are often prescribed together for PAH. While all these therapies dilate the blood vessels to alleviate symptoms, they do little to ameliorate the disease.

As a physician who treated PAH patents two decades ago, Merck’s head of global clinical development, Joerg Koglin, says that current treatments have done little to extend lives.

“When you make that diagnosis, you essentially diagnose a disease that has a pretty high fatality,” Koglin said in an interview with Fierce Pharma. “What has happened over the last 20 years is while we had more and more tools to treat the symptoms of the disease—patients were able to walk a little bit longer and to deal with the disease better—but the mortality hasn’t really moved.”

But that could change with Winrevair. As a first-in-class activin signaling inhibitor, Winrevair acts directly on the underlying problem that causes the disease by targeting a type of protein that promotes inflammatory processes associated with the disease. Winrevair has been shown to modulate vascular cell proliferation, reversing vascular and right ventricle remodeling.

“We’ve learned that this narrowing of pulmonary vessels that leads to those increased pressures in our lungs has to do with an imbalance in signaling factors,” Koglin said. “Once you develop an imbalance, you see an increase in pulmonary pressures and resistance and then all the downstream effects.”

In the phase 3 STELLAR trial, which conducted a 6-minute walk test as the primary endpoint, patients on sotatercept for 24 weeks as an add-on to standard of care improved their exercise capacity by an average distance of 41 meters.

Additionally, sotatercept provided statistically significant improvements in eight of nine secondary measures, including extending the time to a clinical worsening event, such as death, hospitalization or needing substantially more therapy.

“We were able to see a reduction in time to clinical worsening in those events—that’s a Kaplan-Meier analysis—by over 80%. That’s a dramatic effect size,” Koglin added. “And we saw that a substantial number of patients in our studies actually improved on the disease.”

The trial also showed that 24 weeks of sotatercept significantly reduced right heart size and improved right ventricle function and haemodynamic status.

After Bristol Myers Squibb bought out the drug's other developer, Celgene, in 2019, Merck will now make royalty payments to BMS.

Merck is well-suited to commercialize Winrevair as it has had a PH drug on the market for a decade in Adempas, which it shares with Bayer. Analysts have estimated Winrevair's peak sales potential is at least $2 billion, with J.P. Morgan’s Chris Schott estimating it at $3 billion to $4 billion.

J&J controlled half of the $7.3 billion PAH market in 2023. Prophecy Market Insights projects the market will grow by 5.5% annually, reaching $12.2 billion by 2032.

Sotatercept also is under investigation in late-stage trials for PH due to left heart disease and for patients with PAH at intermediate or high risk of disease progression.