If you’re living with pulmonary arterial hypertension (PAH), a type of pulmonary hypertension (PH), there’s promising medical research about new treatments on the horizon. Living with PAH means you’re likely familiar with the standard treatments that have been available for the last decade.

In recent years, researchers have focused on looking for better ways to help those living with PAH live longer, healthier lives. In this article, we will dive into some of the most promising new treatments being studied for pulmonary arterial hypertension.

Current Standard Treatments for Pulmonary Arterial Hypertension

Most of the current PAH treatments work by widening blood vessels or reducing fluid in the body, making it easier for the heart to pump blood through the lungs. Some conventional treatments for PAH and PH include digoxin, calcium channel blockers, diuretics (water pills), blood thinners like warfarin (Coumadin, Jantoven), and supplemental oxygen.

The standard PAH medications may be taken orally, through inhalation, intravenously (delivered into a vein), or subcutaneously (delivered under the skin). Some classes of current PAH medications include:

• Endothelin receptor antagonists (ERAs) — These block a substance in the body called endothelin that causes vasoconstriction (narrow blood vessels). Examples include ambrisentan (Letairis), bosentan (Tracleer), and macitentan (Opsumit).
• Phosphodiesterase 5 (PDE5) inhibitors — These work on the nitric oxide pathway to help vasodilate (relax) the blood vessels, making them wider and increasing blood flow. Examples include tadalafil (Adcirca, Cialis) and sildenafil (Liqrev, Revatio).
• Prostacyclin analogs — These help keep the blood vessels open and blood flowing freely. Examples include epoprostenol (Veletri, Flolan), treprostinil (Remodulin, Tyvaso), iloprost (Ventavis), and a more recently developed prostanoid called selexipag (Uptravi).
• Soluble guanylate cyclase stimulators — These also help widen the blood vessels by stimulating the activity of a protein called guanylate cyclase. An example is riociguat (Adempas).

These treatments focus on the main “pathways” (mechanisms in the body affected by PAH). Think of them like three different roads that medicine can take to help improve how you feel and breathe while living with PAH. While these treatments can help with some symptoms, like shortness of breath or fatigue, they unfortunately cannot cure pulmonary arterial hypertension.

These medications are often taken in different combinations under the guidance of a pulmonologist (a doctor who specializes in lung conditions) or a cardiology provider. They’re not always an ideal option for some people because of the drugs’ intravenous (IV) administration or unwanted side effects.

Recent Advances in Treatment for Pulmonary Arterial Hypertension

Researchers believe PAH is often caused by a combination of genetics, growth factors (protein molecules made by the body to regulate cell division and survival), inflammation, hormones, and even iron levels in the body. By understanding these pathways further, scientists aim to develop treatments that tackle the root causes of PAH, not just its symptoms.

To better understand and organize these new therapies for PAH, we will divide them into groups based on how they work in the body. Researchers are studying each of these specifically for PAH as add-ons to standard therapy.

1. Bone Morphogenetic Protein Signaling Modulators

Bone morphogenetic proteins (BMPs) were first identified for their part in natural bone growth and repair. However, BMPs are now recognized as key players in many body systems. Researchers are currently investigating BMP signaling modulators for their potential to treat pulmonary arterial hypertension. These modulators may be beneficial by promoting healthy growth and maintaining the thickness of pulmonary blood vessels.

BMP signaling modulators aim to decrease thickened pulmonary arteries and improve blood flow to the lungs.

Sotatercept

Sotatercept (Winrevair) was approved by the U.S. Food and Drug Administration (FDA) in March 2024 to treat PAH. It works by balancing cell growth signals in the blood vessels. This mechanism helps decrease thickening of the pulmonary arteries and improve blood flow to the lungs. Studies have found that when used alongside other PAH therapies, sotatercept improves blood flow and increases exercise capacity, as demonstrated by better results in the six-minute walk test.

Sotatercept is a subcutaneous injection, given once every three weeks. This medication offers a newer way of treating PAH. While it comes with risks of side effects and isn’t suitable for all adults with PAH, it works differently than previous therapies and opens the door for targeting underlying mechanisms of PAH.

Elafin

Elafin is a compound that blocks elastase, an enzyme found in higher levels in people with PAH. Elastase breaks down elastin, a structural protein that helps maintain the flexibility and structure of pulmonary blood vessels. When elastin is degraded, it leads to the excessive growth of smooth muscle cells in the pulmonary arteries, making the vessels stiffer and worsening PAH.

In a 2015 study on rats with PAH, elafin was shown to reverse changes in the blood vessels caused by PAH and reduce pulmonary artery pressure. A small trial in healthy humans treated with elafin has been completed, and as of August 2024, another trial is underway.

Tacrolimus

Tacrolimus (Astagraf XL, Envarsus XR, and Prograf) is a medication that reduces inflammation. It’s commonly used as an FDA-approved treatment for people undergoing organ transplants to help their bodies accept a new organ. Since increased inflammation is connected with stiffer vessels, inflammatory reduction with tacrolimus might improve PAH. A small trial in humans with PAH showed that tacrolimus may help improve walking distance for some people. As of August 2024, a larger study is planned to determine which people with PAH may benefit from this targeted therapy.

2. Tyrosine Kinase Inhibitors

Tyrosine kinase inhibitors (TKIs) are drugs that help control the growth of specific cells. They usually target cells we don’t want in the body, like cancer cells, but they are also being tested to see how they could help treat PAH.

Tyrosine kinase inhibitors are typically used to treat cancer, but some are being studied as treatment for PAH.

Imatinib

Imatinib (Gleevec) is an oral TKI medication that’s FDA-approved for multiple forms of cancer, but researchers are currently studying an inhalable version of the medication for treating PAH. While the oral version has been reported to have unpleasant and serious side effects, this new inhaled version may help reduce those side effects while working to help treat PAH.

Seralutinib

Researchers have tested this inhaled medication in clinical trials for safety and effectiveness (how well it works) in people with PAH. In animal studies, it has been shown to reverse some of the changes made to blood vessels caused by PAH. While further research is still needed, the third-phase trial for safety and efficacy in humans with PAH is currently recruiting participants, and it’s scheduled to be completed in October 2025.

3. Bromodomain Inhibitors

Bromodomain proteins (BRDs) help regulate how the body interprets its genetic code. Bromodomain inhibitors work to block the way BRD interprets genetic code for things like cancer and cellular changes that result in the destruction of tissue within the heart and blood vessels.

Bromodomain inhibitors affect the way the body reads its genetic code and work to reduce inflammation due to PAH.

Apabetalone

Apabetalone, a bromodomain inhibitor, is a new oral medication that works in a complex way to reduce inflammation in the body due to PAH. In a small 2022 study, treatment with apabetalone reduced the damaging effects of PAH on the body’s blood vessels. A larger study was set to begin in October 2023 to help confirm these results.

4. Hormone-Targeted Therapy

It’s well known to researchers that females are at higher risk for developing PAH. With this knowledge, scientists have turned to therapies that target estrogen, a hormone associated with female reproductive organs, to determine their potential role in the treatment of PAH.

Tamoxifen

Tamoxifen (Soltamox) is an FDA-approved drug that’s been used to treat estrogen-positive breast cancer for decades. Also available as a generic, tamoxifen is well studied for its safety and efficacy. Researchers completed a study in 2023 to determine if this antiestrogen therapy can potentially help treat PAH, but as of August 2024, they had not published any results.

Anastrozole

Anastrozole (Arimidex) is another medication long approved by the FDA to treat estrogen receptor-positive breast cancer. This medication has also been well studied and is available as a generic.

A large study published in 2024 found that anastrozole was safe for people with PAH. However, the study concluded that the drug didn’t significantly help people with PAH walk farther compared to a placebo.

The Future of Treatments for PAH

While the research for these new treatments is ongoing, many people living with PAH are curious about what is to come in the future. One myPHteam member asked, “Has anyone heard of any new clinical trials coming out that may have the ability to cure this disease?”

Clinical trials play a crucial role in the development of new treatments. By participating in a clinical trial, you can help researchers better understand PAH and potentially gain access to cutting-edge therapies before they become widely available. If you’re considering joining a clinical trial, talk to your doctor to see if it might be a good fit for you.

In the meantime, talk to your doctor about what is working for you and any side effects you may be experiencing on your current therapy. Your doctor will work with you to find the best treatment for your PAH and symptoms.

Talk With Others Who Understand

On myPHteam, the social network for people with pulmonary hypertension and their loved ones, more than 55,000 members come together to ask questions, give advice, and share their stories with others who understand life with pulmonary hypertension.

Are you curious about new treatments for pulmonary arterial hypertension? What has your current treatment experience been like? Share your experience in the comments below, or start a conversation by posting on your Activities page.