Sotatercept Shows Promise in Group 3 Chronic Lung Disease Pulmonary Hypertension

Chronic lung disease-associated pulmonary hypertension (CLD-PH) remains one of the most difficult forms of pulmonary hypertension (PH) to treat, with limited therapeutic options and poor long-term outcomes. New real-world findings presented at the 2026 American Thoracic Society (ATS) International Conference in Orlando suggest sotatercept may offer clinical benefit beyond its currently approved indication in group 1 pulmonary arterial hypertension (PAH).

In an interview with HCPLive at ATS, Krunal Patel, MD, of Temple University Hospital, discussed data from a single-center cohort evaluating sotatercept in patients with group 3 CLD-PH. The analysis demonstrated improvements across hemodynamic, functional, and echocardiographic parameters, including reductions in pulmonary vascular resistance (PVR), mean pulmonary artery pressure (mPAP), oxygen requirements, and BNP levels, alongside improvements in 6-minute walk distance (6MWD) and right ventricular (RV) remodeling.

“At the end of the day, it’s all patient outcomes,” Patel said. “You want to make sure the patient is feeling better. Out of all of those parameters, I think the 6-minute walk distance will have the greatest impact because that’s what’s actually going to affect the patient.”

The retrospective analysis included 16 patients with CLD-PH treated with sotatercept at a tertiary PH referral center. Investigators compared pre- and post-treatment assessments, including right heart catheterization, BNP, NYHA functional class, oxygen requirement, 6MWD, and transthoracic echocardiography findings.

Among patients with paired hemodynamic data, right atrial pressure fell from 7.1 mmHg to 3.8 mmHg, while mPAP declined from 47.9 mmHg to 30.7 mmHg and PVR decreased from 10.4 to 6.0 Wood units. Cardiac output increased from 3.46 L/min to 4.81 L/min. BNP levels also declined substantially, from 378 pg/mL to 92 pg/mL.

Functionally, oxygen requirements decreased from 5.4 to 4.2 L/min, and 6MWD improved from 211 meters to 252 meters. Patel noted the functional improvements may ultimately carry the greatest clinical significance for patients.

One of the most notable findings involved evidence of RV remodeling reversal on echocardiography. Patel described substantial improvements in RV dilation and systolic function after approximately 1 year of therapy.

“That’s probably the biggest outcome that we saw,” Patel said. “Patients before sotatercept initiation would have severe RV dilation and reduced RV systolic function, and then after initiating sotatercept, we saw improvement in RV remodeling. Some patients almost had full recoverability of their RV function.”

The cohort size remains small, however, and Patel emphasized the findings should be viewed as an early proof-of-concept rather than practice-changing evidence. Patel said they have continued to collect data since submitting the abstract and have observed similar results.

Investigators also observed modest hemoglobin increases in most patients, consistent with the known safety profile of sotatercept. Patel noted this occasionally required treatment interruption or dose reduction, particularly because many group 3 PH patients already have elevated baseline hemoglobin levels related to chronic hypoxemia.

“Even with interruptions and dose reductions, we still saw significant improvement in the hemodynamics,” Patel said.

According to Patel, the next step will require larger prospective placebo-controlled studies to determine whether the observed benefits can be replicated in broader CLD-PH populations. Still, Patel suggested the observed RV recovery may represent the most compelling signal from the early experience with sotatercept in this difficult-to-treat population.

“The big takeaway was…[the] significant RV remodeling and improvement in RV function,” Patel said. “[That’s] a huge step in treatment when it comes to pulmonary hypertension patients in the chronic lung disease cohort.”

References

Patel K, Rali P, Tovar M, et al. (Poster Board # P1303) Novel Real World Use of Sotatercept in Group 3 Chronic Lung Disease Pulmonary Hypertension Patients. Poster presented at ATS 2026 in Orlando, Florida, on May 19.