Pulmonary arterial hypertension, a disease that leads to worsening lung and heart problems that eventually become life-threatening, is treated with drugs that alleviate symptoms. FDA approval of a new Merck drug marks the first for a therapy addressing an underlying cause of the disease.
The Tuesday approval of the Merck drug covers the treatment of adults whose pulmonary arterial hypertension (PAH) is at intermediate or high risk of progression. The drug, known in development as sotatercept, will be marketed under the brand name Winrevair.
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Hypertension—high blood pressure—is common. PAH is a rare form of hypertension that specifically affects the arteries carrying blood from the right side of the heart and into the lungs. The narrowing of these blood vessels slows blood flow to the lungs and raises blood pressure. Consequently, the heart must work harder to pump blood through the lungs. The disease can lead to heart failure.
Patients who have PAH experience shortness of breath, fatigue, and chest pain. Once the condition starts, it gets progressively worse, leading to hospitalization and potentially death. The drugs already available to treat PAH work by relaxing or widening blood vessels to improve blood flow. Winrevair is based on research indicating that an imbalance in cell signaling leads to the proliferation of cells that thicken the insides of pulmonary vessels. A protein called activin is elevated in PAH patients, tipping the cell signaling balance toward cell proliferation. Winrevair is a fusion protein engineered to trap activins and other proteins associated with PAH.
A Phase 3 clinical trial evaluated Winrevair in addition to standard of care PAH treatment. The drug’s efficacy was measured with a walk test, a common way to assess cardiovascular medications. The main goal was to measure the change in how far patients can walk in six minutes after 24 weeks of treatment with the drug, administered as a subcutaneous injection every three weeks.
Results for the main goal showed the median change in walk distance in the study drug arm was 34.4 meters compared to a median 1.0 meters in the placebo group. The study also achieved statistical significance for eight of nine secondary goals, including one that showed an 84% reduction in death from any cause in the Winrevair arm compared to the placebo group. The improvements were maintained over 18 to 24 months of continued treatment with the drug. Phase 3 data were published last year in the New England Journal of Medicine.
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“New treatment options continue to be needed for patients with pulmonary arterial hypertension that support important clinical goals, including increasing exercise capacity and improving functional class,” Dr. Aaron Waxman, executive director of the Center for Pulmonary Heart Diseases at Brigham and Women’s Hospital and an investigator on the Merck drug’s Phase 3 study, said in a prepared statement. “Sotatercept added to background therapy has the potential to become a new standard of care option for patients with pulmonary arterial hypertension.”
The most common adverse events reported from clinical testing included bleeding in the nose and gums, abnormally low platelet levels, and higher hemoglobin levels. Winrevair’s label advises clinicians to check hemoglobin and platelet levels before the first five doses and then monitor those levels periodically thereafter. The dose can be adjusted to mitigate these complications.
[Paragraph added with analyst comment.] In a note sent to investors on Wednesday, Leerink Partners analyst Daina Graybosch characterized Winrevair’s label as a win for the drug. The approval covers the treatment of PAH patients broadly, which is important for reimbursement, she said. The label carries no black box warning for toxicities. As for the bleeding events observed in clinical trials, the FDA said they are more likely in those who are also taking other therapies. While the label includes monitoring requirements, Graybosch noted that this monitoring focuses on patients receiving these combination therapies and those with low platelet counts. Another win for the drug: the approval includes home administration by the patient or a caregiver after training on how to do it.
Winrevair came to Merck via the $11.5 billion acquisition of Acceleron Pharma in 2021. The new PAH drug is important for Merck, which is looking for products to make up for coming revenue declines as patents expire later this decade for the cancer immunotherapy Keytruda, its top-selling product.
Merck said it expects Winrevair will become available by the end of April. It will supply the PAH drug in single-vial or double-vial kits priced at $14,000 per vial. Based on experience with the drug in clinical trials, the company expects about two-thirds of patients will use the single-vial kits. That means that given every three weeks, the annual cost of Winrevair will top $242,000. The Institute for Clinical and Economic Review, a nonprofit group that keeps watch on drug prices, calculated the Merck PAH drug would be cost effective priced in the range of $17,900 to $35,400 a year. Merck said a patient’s out-of-pocket cost depends on many factors, including details of an insurance plan, which may include an out-of-pocket maximum.
Winrevair is still under regulatory review in Europe. Clinical trials are underway that could expand the use of Winrevair. Phase 3 studies are ongoing in additional groups of PAH patients; a Phase 2 study is testing the drug in another type of pulmonary hypertension.
Merck has another PAH drug candidate, MK-5475. This small molecule formulated as an inhalable medication targets an enzyme to induce relaxation of blood vessels. MK-5475 is currently in Phase 2/3 testing. Other companies with PAH drugs in various stages of clinical development include Aerovate Therapeutics, Gossamer Bio, Keros Therapeutics, and Novartis.
