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A new breakthrough therapy for Pulmonary Arterial Hypertension

Sotatercept could alter the course of disease for 45,000 U.S. patients


From the Editors


Quarterly Drugs to Watch Report

Anticipated Launches | Q1 2024

Download the report (PDF)


A new drug in the pipeline could bring improved quality of life to tens of thousands of people suffering from Pulmonary Arterial Hypertension (PAH). Sotatercept (Merck) is a first-in-class activin receptor fusion protein subcutaneously administered every three weeks; it has received Breakthrough Therapy designation from the U.S. Food and Drug Administration (FDA) for the treatment of PAH.*



Pulmonary hypertension is a rare and progressive disease that occurs when the pressure in the blood vessels leading from the heart to the lungs is too high.

Symptoms of pulmonary hypertension include shortness of breath, fatigue, chest pain, edema, light-headedness, and/or palpitations. It is likely underdiagnosed because symptoms can be mistaken for more common medical problems such as asthma or chronic obstructive pulmonary disease. If left untreated, pulmonary hypertension can lead to right heart failure and death.

There are five types of pulmonary hypertension based on different causes ranging from infectious diseases, underlying lung illnesses, and certain autoimmune conditions as well as unknown reasons.

World Health Organization (WHO) Group 1 pulmonary hypertension refers to Pulmonary Arterial Hypertension (PAH), which is caused when the arteries in the lungs become narrowed, thickened, or stiff. The five-year mortality rate for patients with PAH is approximately 40 percent.


Prevalence and disease burden

PAH makes up about 5 percent of all pulmonary hypertension cases and there are an estimated 45,000 patients diagnosed with PAH in the United States. Although PAH can affect all ages, races, and ethnicities, women are four times more likely to develop PAH than men. The mean age at diagnosis is ~50 years of age.

Within PAH, patients are further stratified by risk based on the WHO functional class. This characterizes patients into four classes based upon their functional ability according to symptoms of PAH. Patients in WHO class I do not have limitations or experience symptoms with ordinary physical activity. Conversely, patients in WHO class IV are unable to carry out any physical activity without symptoms and symptoms may be present at rest.

PAH is treatable, although not currently curable. But it is difficult – and expensive – to manage. The cost of treatment can average between $2,200 and $9,300 per month; significant pharmacy costs are driven by high drug utilization.1 Many patients are on multiple medications.


46% of patients takes two medications for PAH; 9% take three2


Several PAH-specific drugs rank among the world’s costliest medications.


Treatment landscape

The primary goals of PAH treatment include alleviation of symptoms, improved exercise capacity, improvement in quality of life, preservation of heart function, and reduction of mortality risk.

Beyond supportive therapy, current treatment strategies work by promoting vasodilation (widening of blood vessels). These include:

  • phosphodiesterase-5 (PDE5) inhibitors
  • guanylate cyclase stimulators
  • endothelin receptor antagonists (ERAs)
  • prostacyclin therapies

Patients with moderate to severe disease are often treated with dual therapy consisting of an ERA and a PDE5 inhibitor or a guanylate cyclase stimulator. For patients who progress on dual therapy, a prostacyclin therapy may be added to maximize medical therapy prior to considering a lung transplant.


The PAH pipeline

In addition to sotatercept, other drugs in the late-stage pipeline to treat PAH include:

  • Yutrepia (treprostinil, Liquidia Technologies) – prostacyclin agonist to improve exercise ability in adults with New York Heart Association functional class II-III symptoms. FDA review date: March 31, 2024
  • Opsynvi (macitentan/tadalafil, Acetlion/Johnson & Johnson) – ERA/PDE5 inhibitor for the treatment of PAH in adults with WHO functional class II–III. FDA review date: March 30, 2024


The promise of sotatercept

Currently pending approval for the treatment of PAH, sotatercept has the potential to reverse the characteristic vascular remodeling that underlies PAH pathology. Current treatment options are unable to do this.

In a late-stage trial in patients with symptomatic WHO functional class II or III PAH, sotatercept significantly improved the six-minute walk distance from baseline at 24 weeks by nearly 41 meters versus placebo at week 24. Additionally, there was an 84 percent lower risk of death or nonfatal clinical worsening event. Most patients were already receiving triple therapy (60 percent) or double therapy (34.4 percent) at baseline.**

The cost of sotatercept is estimated at $25,000 to $30,000 per month. CVS Caremark has a range of solutions to help payors manage the costs of PAH treatment while ensuring that patients receive the right drug at the right time.

The anticipated FDA review date is March 2024. If approved, sotatercept would be the first non-vasodilator therapy for PAH and would provide a potentially disease-modifying add-on therapy for patients on standard background therapy.


  • 1 Sikirica M, Iorga SR, Bancroft T, Potash J. The economic burden of pulmonary arterial hypertension (PAH) in the US on payers and patients. BMC Health Serv Res. 2014;14:676. Published 2014 Dec 24. doi:10.1186/s12913-014-0676-0

  • 2 Highland KB, Hughes KE, Williams KJ, Kyei-Baffour B, Ferguson S. Ensuring appropriate access to pulmonary arterial hypertension therapy. Am J Manag Care. 2019;25:S119-S127


* This designation is intended to expedite the development and review of drugs that are intended to treat a serious condition and for which preliminary evidence indicates substantial improvement over available therapies.

** Adverse effects that occurred at rates greater than placebo included bleeding events (21.5 percent), telangiectasia (appearance of small blood vessels on the skin, 10.4 percent), and increased hemoglobin level (5.5 percent).

This document contains references to brand-name prescription drugs that are trademarks or registered trademarks of pharmaceutical manufacturers not affiliated with CVS Health.

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