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Pulmonary Arterial Hypertension: Her Symptoms Were Getting Worse. Then She Joined A Clinical Trial
Heather Kauffman, 49, says she entered a clinical trial for a new drug to treat pulmonary arterial hypertension (PAH) in 2021 with a dose of cautious optimism.
Her physician, Dr. Vallerie McLaughlin, a leading expert in pulmonary hypertension at the University of Michigan Medical School, first approached her two years earlier with the possibility of enrolling in the phase III STELLAR study for a new drug to treat PAH.
Kauffman's work schedule made it hard for her to commit to the study, but when her day-to-day health continued to worsen, she agreed to do it.
For Kauffman, PAH (a rare form of pulmonary hypertension that can be life threatening) has been a throughline stretching across her whole life. During childhood, her younger brother, BJ, passed away at just five years old from the condition.
By the time she was diagnosed at the end of 2017, it was a grim discovery to learn she and BJ shared the same disease, bringing with it personal fears over her own health.
Flash forward to 2024, and Kauffman describes her experience in the STELLAR trial to be, well, "stellar."
The drug, sotatercept, was designed to treat adults with PAH to increase exercise capacity, improve WHO functional class (FC), and reduce the risk of clinical worsening events.
The Merck-manufactured drug – an injectable administered every three weeks that is sold under the brand name Winrevair – was just approved in March by the Food and Drug Administration (FDA), according to a release.
This first-in-class activin signaling inhibitor marks a significant milestone in tackling the condition. Along with the recent FDA approval of Opsynvi, which is a daily tablet that combines existing drugs macitentan and tadalafil, it's currently a promising period for PAH treatment.
Sotatercept marks the first time in nearly a decade that a brand-new PAH treatment has been approved.
"I had told [Dr. McLaughlin] from the very beginning, 'my brother passed away in 1982, there was nothing for him, there was nothing that they could do,'" Kauffman told Healthline. "So, I had told her that I would like to be part of research…and be part of anything that would further the research of this disease."
PAH is a condition that causes a narrowing of the blood vessels in your lungs, resulting in impaired blood flow throughout the lungs.
People living with PAH will develop high blood pressure in the pulmonary arteries that need to transport blood deficient in oxygen from the heart to the lungs, according to the National Heart, Lung, and Blood Institute.
Those with PAH will see their hearts overexert themselves as they try to work in overdrive to pump blood to the lungs. This can have a negative domino effect on your overall health. When left untreated, the condition is fatal.
The condition is very rare. Only 500 to 1,000 people are diagnosed with PAH annually in the United States.
When asked to put in context how PAH differs from other forms of pulmonary hypertension, Dr. Kristin Highland, a specialist in pulmonary medicine at Cleveland Clinic who was also part of the sotatercept clinical trial, explained that there are various features that overlap between the different groups that fall under the wider pulmonary hypertension umbrella. PAH is classified as "group 1."
Highland told Healthline that "group 2" pulmonary hypertension is the most common type, known as "post-capillary," with pressures elevated on both the right and left sides of the heart. PAH, along with groups 3 and 4, are considered pre-capillary forms of pulmonary hypertension, meaning that "left-side of the heart, and left-sided pressures, are normal."
All groups have abnormalities of lung blood vessels, and PAH "is a diagnosis of exclusion," meaning doctors will cross out associations with the other groups (like group 3 being the result of pulmonary disorders like chronic hypoxia or group 4 resulting from blood clots that break off elsewhere in the body, lodge in the lungs, and then fail to dissolve, for two examples) to derive a PAH diagnosis.
"In PAH, the lesion is confined to the pulmonary arteriole with abnormalities of all layers of the blood vessel that results in a vasculopathy, or thickening and narrowing, of the blood vessel, which then increases the resistance in the pulmonary vascular bed leading to pulmonary hypertension, or increased pressure in the lung," Highland added. "This eventually culminates in the right heart failing in its ability to pump blood through the lungs."
Highland explained that one challenge that comes from this condition is that PAH can often be misdiagnosed or underdiagnosed due to the fact that symptoms can resemble those of other conditions.
She said there is often a delay in diagnosis that stretches more than two years.
While living with PAH, Highland said patients often subconsciously "slow down" in response to their symptoms. This means the condition might be missed entirely by a doctor until someone does something out of character, like go on an arduous hike.
"When patients are breathless at rest, they have extremely advanced disease," Highland explained. "Common things being common, patients are usually diagnosed with asthma, COPD, left heart failure, being obese, and out of shape."
She said that as the disease advances, the right heart becomes further strained, and the individual might experience fatigue, chest pain, swelling of the stomach or lower extremities, dizziness, or fainting, among other symptoms. Highland noted that fainting may "indicate the right heart is really struggling."
Thinking back to the time right before her diagnosis, Kauffman said she thought her symptoms were tied to anxiety because her husband had just been deployed to the Middle East. She would experience shortness of breath, and her heart would race.
She noticed just going to work seemed to expend a lot of oxygen, and she would even have to sit in the car and take a break before heading in to the office.
She went to the urgent care and ultimately was admitted to the ER. She was diagnosed with PAH three days later.
She calls it "fate" and a "series of fortunate events," given the reality that most people go two or three years before a diagnosis.
According to the release, Winrevair will be available in specialty U.S. Pharmacies by the end of April.
When asked how significant it is to have this new treatment available on the market, McLaughlin, Kauffman's doctor who enrolled her in the trial, said it's exciting to have this new drug. Everything in the past 30 years targeted "the same three pathways," she explained, and "this is the first agent that really has the potential to reverse remodel the disease."
"I think this is a huge step. It's really exciting to have a drug that starts getting at the underlying molecular issues with the disease and might have some anti-proliferations and reverse modeling," McLaughlin added. "The breadth of the trial positivity was incredible…We are very excited about what it really marks, which is more advancements, right? We are learning more and more about PAH every day, and to have companies invest in our space and develop drugs with novel mechanisms of actions is really fantastic."
She said there are currently "a number of other clinical trials" taking place, and she expects more PAH medications will be available in the near future.
Highland pointed out that the first FDA-approved drug PAH, epoprostenol, wasn't available until 1996. That means there were countless other people like Kauffman's brother BJ who were living with this disease with no treatment in sight. Before that first drug's approval, Highland said the expected survival of someone with PAH was under three years.
"The available therapies for PAH since then have focused on vasodilation, although most of these drugs have pleiotropic effects. The three classes of drugs have focused on augmenting the prostacyclin pathway or the nitric oxide pathway or blocking the endothelin pathway," Highland added. "Patients usually need to be on combination therapy. Patients also often need to be on diuretics and oxygen. Pulmonary rehabilitation is also very beneficial."
Highland added that while this is an encouraging time, survival for PAH is estimated to be at just 86% at the one-year marker, 67% at the three-year marker, and only 54% at five years, according to a French registry. Highland stressed that this reality for people diagnosed with PAH means "additional and more effective therapies are needed."
Since being on the drug, Kauffman said she's noticed a "night and day" difference in managing her symptoms. She recalls going in for her first shot in August 2021, and she just knew she had received the drug and not the study's placebo.
"Immediately that night, my breathing changed. It wasn't, like, drastic, but I felt different, and then, the next day, I slept for like 22 out of the 24 hours," she recalled. "For each shot, things were getting better and better."
Once on the medication, Kauffman said she was walking farther and able to do more. Her daughter plays travel softball, and she was able to go with her on weekends and participate with the other parents and families.
However, Kauffman emphasized this is not a cure. She is also on other medications with side effects that give her extreme leg pain, which she said brings her more discomfort than PAH at the moment.
"I'm no longer thinking like I'm not going to be here. I'm looking forward to things," Kauffman said of past fears that she might not have many years left with her family. "My daughter is going to be 16, and it's just things like that. I'm just super hopeful. I just feel better."
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Winrevair Gains Approval For Pulmonary Arterial Hypertension, But High Price Could Limit Uptake
Having the rare disease pulmonary arterial hypertension increases the risk of blood clots in the ... [+] lungs' small arteries.
gettyThe Food and Drug Administration approved Winrevair last week. The drug is indicated for a rare and deadly cardiovascular disorder called pulmonary arterial hypertension. PAH has long been challenging to treat, as STAT News reports. As such, Winrevair represents a potentially important breakthrough.
The approval of Winrevair (sotatercept) comes on the heels of the FDA's licensing of another PAH treatment, a tablet called Opsynvi which combines macitentan and tadalafil.
Winrevair could be disease-modifying—it decreases the likelihood of worsening clinical events—as it inhibits a growth factor that is overproduced by people with PAH. This leads to thickening of the walls of blood vessels, which in turn can cause high blood pressure and a heavy strain on the heart due to constriction of lung arteries.
The New England Journal of Medicine published Phase 3 trial data which showed adults with PAH who were given sotatercept achieved greater improvement in six-minute walk distance,* experienced better overall functioning and had a significantly (84%) reduced risk for clinical deterioration or death at 24 weeks compared with the placebo group. Here, a person's functioning is measured on a World Health Organization-designated scale of "functional classes." There are four such classes that are used to rate how ill PAH patients are. The higher the class the more severe the disease and the greater the urgency for the patient to be accurately diagnosed and started on therapy.
PAH affects around 40,000 people in the U.S. And 43% of patients die within five years of diagnosis.
Up to 50% of PAH patients may be eligible for Winrevair. The drug is expected to be used as a second- or third-line therapy, but eventually may have first-line potential, according to FirstWord Pharma.
Winrevair should arrive on (specialty) pharmacy shelves by late April, Healio reports. The therapeutic is injected once every three weeks and can be self-administered by patients. It remains an open question whether people prescribed sotatercept will need to still take the cocktail of drugs that help ease symptoms.
The drug's sponsor, Merck, will sell Winrevair for a list price of approximately $14,000 per vial or roughly $240,000 a year, depending on a person's weight. This figure does not account for certain discounts to payers which will be factored into the net price.
The high annual list price puts Winrevair well above commonly cited cost-effectiveness thresholds, even when accounting for the benefits if confers. The cost-effectiveness watchdog, the Institute for Clinical and Economic Review, considered the use of sotatercept added to existing therapy among adults with PAH versus existing therapy alone and concluded that if Winrevair had a net price of between roughly $18,000 and $35,000 a year, it would meet typical thresholds.
Since it's highly unlikely the net yearly price of Winrevair will be close to the $18,000 to $35,000 range, this may be considered problematic by payers and pharmacy benefit managers. To reduce their financial exposure, it's plausible they will impose a set of utilization tools, including placement of the drug in a relatively high patient cost-share tier, extensive use of prior authorization and possibly step edits (a cheaper drug may have to be tried first prior to Winrevair being covered). They could also exclude from coverage certain patients assigned to a low or less severe WHO functional class. Finally, payers may apply duration limits while assessing dose titration, side effects and disease progression.
For those who take the drug and are on Medicare, Pink Sheet noted that the soon-to-be implemented $2,000 out-of-pocket cost-sharing cap will help lower their financial burden. This cap comes into force in 2025 as part of the Inflation Reduction Act's redesign of Medicare's outpatient (Part D) pharmacy benefit. At the same time, however, as part of the Part D overhaul in 2025 pharmaceutical manufacturers will face a 20% mandatory price discount in the so-called catastrophic or high-cost phase of the Medicare drug benefit. In addition, given that payers will soon be responsible for managing a much higher share of the cost of pharmaceuticals, they will probably impose utilization restrictions that may limit access.
The newly approved Winrevair is a promising therapy for PAH patients. Its high price and correspondingly limited cost-effectiveness could, however, restrain its uptake.
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