FDA approves sotatercept, now Winrevair, to treat PAH in adults
Injection therapy expected in US specialty pharmacies by end of April
The U.S. Food and Drug Administration (FDA) has approved the under-the-skin injection therapy sotatercept-csrk — to be marketed under the brand name Winrevair — to treat adults with pulmonary arterial hypertension (PAH).
The now-approved treatment is expected to be available for dispensing by select U.S. specialty pharmacies by the end of April, according to Merck, which has owned the rights to the biologic therapy since acquiring prior developer Acceleron Pharma in 2021.
Winrevair specifically is intended to enhance exercise capacity, improve World Health Organization (WHO) functional class, and reduce the risk of clinical worsening events in patients. Clinical trial data has shown the benefits of adding Winrevair to background PAH therapy.
“This approval of Winrevair is an important milestone and a testament to our science-led strategy and focus on the development of innovations that can help people affected by rare diseases like PAH. We are proud to bring this novel medicine to patients,” Eliav Barr, MD, senior vice president and head of global clinical development, as well as chief medical officer, at Merck Research Laboratories, said in a company press release.
Winrevair is given once every three weeks by subcutaneous, or under-the-skin, injection and may be administered by patients or caregivers provided they are given guidance and training, and are monitored by a healthcare provider. Healthcare providers, patients, and caregivers are advised to check the Instructions for Use booklet that comes with the therapy to know how to correctly prepare and administer Winrevair.
Merck to offer patients information, insurance help on Winrevair
The medication comes in two dosages, 45 mg and 60 mg, both in single-dose vials; the recommended starting dose is 0.3 mg/kg and the target dose is 0.7 mg/kg.
Patients prescribed Winrevair will have support from Merck — which includes information about insurance coverage and help with out-of-pocket costs — through the Merck Access Program. More information can be found by calling 1-888-637-2502 or visiting www.merckaccessprogram-WINREVAIR.com in the coming days.
Pulmonary arterial hypertension is marked by increased pressure in the vessels that carry blood through the lungs to pick up oxygen. In PAH, the cells that line the inside of these blood vessels grow more than normal, which narrows the blood vessels and ultimately increases pressure. This abnormal cell growth is driven by signaling molecules called growth factors.
The active agent in Winrevair is essentially a fragment of a growth factor receptor that’s designed to act as a trap to sponge up excess growth factors, thereby reducing excess cell growth.
Merck notes that the FDA approval of Winrevair makes it the first available activin signaling inhibitor for PAH in the U.S. This class of therapy improves the balance between pro- and anti-proliferative signaling to regulate the vascular cell growth that drives PAH.
“This approval is an important milestone, as it offers healthcare providers a novel therapeutic option that targets a new PAH treatment pathway,” said Marc Humbert, MD, PhD, an investigator on the Phase 3 STELLAR clinical trial (NCT04576988) that supported Winrevair’s approval. Humbert also is a professor of medicine and the director of the Pulmonary Hypertension Reference Center at the Université Paris-Saclay, in France.
The STELLAR study enrolled 323 adults with PAH, and participants were given either Winrevair or a placebo, in addition to standard treatments, for about six months. Winrevair was administered by subcutaneous injection every three weeks, starting at a dose of 0.3 mg/kg, and then increasing up to 0.7 mg/kg.
FDA approval welcomed by PH advocates, community
The trial’s main goal was to test whether Winrevair could outperform the placebo on the six-minute walk test, a common assessment of exercise capacity that simply measures how far a person can walk in six minutes. Participants given Winrevair could walk on average 41 meters (134.5 feet) further than those given the placebo by the end of the six-month study, the results showed.
Data from the trial also indicated that Winrevair treatment improved measures of heart health and reduced the occurrence of death or PAH clinical worsening events by 84% compared with the placebo. Further, the therapy improved the WHO functional class in a significantly greater percentage of participants (29% vs. 14%).
Importantly, a mathematical model built based on data from STELLAR predicted that adding the treatment to the standard of care could extend patients’ lifespans by more than a decade.
Sotatercept [now Winrevair] added to background therapy has the potential to become a new standard of care option for patients with pulmonary arterial hypertension.
“Based on the Phase 3 STELLAR trial, adding Winrevair to background PAH therapy demonstrated significant clinical benefits compared to background PAH therapy alone,” Humbert said.
Another investigator in STELLAR, Aaron Waxman, MD, PhD, said “sotatercept [now Winrevair] added to background therapy has the potential to become a new standard of care option for patients with pulmonary arterial hypertension.”
“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,” said Waxman, who also serves as the executive director of the Center for Pulmonary Heart Diseases at Brigham and Women’s Hospital, in Boston.
The most common side effects of Winrevair include nosebleeds, widened skin blood vessels, headache, diarrhea, rash, dizziness, and skin redness. Nearly 1 in 4 patients in the STELLAR trial developed antibodies against the therapy, but data suggested these did not affect its safety or efficacy.
Winrevair’s approval was met with enthusiasm by the pulmonary hypertension community.
“The Pulmonary Hypertension Association welcomes the development of new therapies for those with PAH,” said Matt Granato, the nonprofit’s president and CEO.
“A diagnosis of PAH is a life-changing experience for patients and families due to its chronic, progressive nature,” Granato said. “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.”
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