MSD leaps on FDA approval of PAH drug sotatercept

MSD’s sotatercept has become the first FDA-approved therapy for pulmonary arterial hypertension (PAH) that addresses the underlying mechanism behind the disease, rather than its symptoms.

The first-in-class activin receptor type IIA-Fc (ActRIIA-Fc) fusion protein, given the trade name Winrevair, has been cleared to improve exercise capacity, improve lung function, and reduce the risk of worsening clinical events in adults with PAH after a priority review.

PAH is a life-threatening disease, caused by the narrowing of blood vessels in the lungs, which is currently treated mainly with drugs that dilate the blood vessels, like endothelin antagonists and prostacyclin analogues, as well as phosphodiesterase inhibitors to increase blood flow through the lungs.

Winrevair is thought to work by blocking abnormal signalling between cells in the pulmonary blood vessels, which scientists think could lead to a partial reversal of the disease process in PAH. MSD – known as Merck & Co in the US and Canada – has predicted sales of the drug could reach upwards of $3 billion a year, while some analysts think that it could make $5 billion or more.

Shares in the company rose nearly 5% in after-hours trading following the approval announcement. Winrevair is a key component of the pharma group’s strategy to generate $10 billion in cardiovascular disease therapy sales in the 2030s, and also one of the drugs that could help it prepare for the loss of patent protection on $25 billion cancer blockbuster Keytruda (pembrolizumab) in 2028.

The approval had been widely anticipated after the results of the STELLAR trial, which showed 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.

That increase in survival is seen as a major advance in PAH treatment, which has a five-year survival rate of a little over 40%, and is backed up by functional improvements, including a significant 40.8-metre increase in exercise capacity, measured using the six-minute walking test (6MWT).

Winrevair has been approved with a recommendation that patients are monitored for haemoglobin and platelet levels before and during treatment, as it has been linked to increased haemoglobin levels that may lead to high levels of red blood cells (erythrocytosis) that could raise the risk of clotting and other side effects.

In addition to STELLAR, 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 due to left heart disease. There are estimated to be around 40,000 to 60,000 people in the US living with PAH.

MSD 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.

The company said it plans to launch Winrevair by the end of next month and has set a list price of $14,000 per vial. The drug is administered as a subcutaneous injection every three weeks, and MSD says it expects that most patients will need a single vial, for an annual cost of about $243,000 before any discounts or rebates.

That is well above the $17,900 to $35,400 per year cost-effectiveness range that the Institute for Clinical and Economic Review (ICER) modelled in a report published in January, which nevertheless assumed a “placeholder” price of $400,000 for the drug and estimated that 7% of the eligible patients in the US could be treated within five years without crossing the ICER potential budget impact threshold of $777 million per year.

“A diagnosis of PAH is a life-changing experience for patients and families due to its chronic, progressive nature,” said Matt Granato, president and chief executive of Pulmonary Hypertension Association (PHA).

“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,” he added.

Winrevair’s approval comes a few days after the FDA approved Johnson & Johnson’s Opsynvi, a fixed-dose combination of endothelin antagonist macitentan and PDE-5 inhibitor tadalafil. J&J sells macitentan on its own as Opsumit, currently a top-selling drug for PAH with sales of $2 billion a year, and also makes $1.6 billion from prostacyclin analogue Uptravi (selexipag).