New FDA-approved drug for pulmonary arterial hypertension targets disease modification instead of just symptoms

With a stage III study already complete, MUSC is participating in a new study that looks at early intervention – the potential to alter the pace of disease progression rather than play catch-up

by Celia Spell

The idea is to impact the process driving the remodeling of blood vessels in the lungs.

In pulmonary arterial hypertension, or PAH, the walls of the blood vessels within the lungs thicken due to unchecked cell proliferation. This exuberant cell multiplication reduces the space inside the blood vessel, which then increases the resistance to blood flow through the lungs. It often presents in patients as shortness of breath, chest pain and lightheadedness.

A new drug from Merck known as WINREVAIR™ (sotatercept-csrk), was approved by the Food and Drug Administration this past spring. MUSC’s pulmonary vascular disease (PVD) program contributed to the research that led to the development of the new drug and is currently a site for the medication’s ongoing HYPERION clinical trial.

PAH is part of a larger group of diseases called pulmonary hypertension, according to the National Heart, Lung, and Blood Institute, and is considered a progressive and often fatal disease. Rahul Argula, M.D., director of MUSC’s PVD program, works with his patients from the time of diagnosis and spends time tinkering and adjusting the doses of their various medications in an effort to stay ahead of the disease. He dreads the day he has to tell them that he has exhausted all treatment options.

“When they’ve worked hard and done exactly what you’ve asked of them and endured the medication side effects as well as the financial hardships of medication costs, it is hard to tell them that there are no other options left,” he said. “This new medication is truly exciting. It is the first major step in creating another treatment pathway for PAH patients.”

Traditional therapies for PAH focus on vasodilators, which relax the lung’s blood vessels in an effort to create more space for blood flow. “Vasodilators have pretty much been the cornerstone of PAH therapy for the past three and a half decades,” Argula said. “For the first time, we’re asking, what if we blunted the proliferative signal that causes the lung’s blood vessels to become diseased?”

Normal lung blood vessels maintain a balance of cellular signals and mechanisms that tell cells when it’s time to multiply or when it’s time to stop. Research over the past two decades has identified that a significant number of patients with PAH have a defective “brake pedal,” known as the BMPR II receptor. Without it, cells within the walls of the lung’s blood vessels have unchecked cell multiplication.

The new approach to treating PAH focuses on the other side by counteracting the “accelerator pedal” that drives proliferation.

MUSC participated in the STELLAR trial, which was published in the New England Journal of Medicine last summer. “The positive results of the STELLAR trial gave hope to clinicians and researchers that this drug might be here to stay,” Argula said.

The STELLAR trial was designed for patients who had exhausted their therapy options and were farther along in their disease progression. The HYPERION trial is currently accepting patients at MUSC and is designed for newly diagnosed patients who are at a much earlier stage in their disease trajectory.

WINREVAIR™ is currently available to PAH patients at MUSC.

Argula says he has three priorities for this new medication: He wants as many patients to have access to it as possible, he wants to continue compiling information on the drug to amplify its effectiveness and understand any potential harm to patients, and lastly, he wants to explore its use in patients with other types of pulmonary hypertension, if possible.

“There are many other systemic diseases that cause pulmonary hypertension, but we don’t have good treatments for them,” he said. “My own research passion is systemic sclerosis, or scleroderma as it is more commonly known, which also causes PAH, but we don’t know how effective WINREVAIR™ is in that population.”

He hopes that with all the trials underway for this medication, more and more patients can have hope for better drugs to treat their PAH disease progression. He is glad that the MUSC PVD program has been part of that process in the development of this new therapy for both its own patients and other patients worldwide with pulmonary arterial hypertension.