PAH treatment seralutinib shows benefits over nearly 1.5 years: Trial
New data 'underscore seralutinib’s potential,' per developer
Seralutinib, an inhaled therapy for pulmonary arterial hypertension (PAH) in the pipeline of Gossamer Bio, continues to reduce the resistance blood faces moving into the lungs when added to standard of care treatment for PAH, according to data from a long-term extension part of a Phase 2 clinical trial.
The data show the benefits of seralutinib treatment over nearly 1.5 years, according to the company. The results were presented by Gossamer at the Pulmonary Vascular Research Institute 2025 Annual Congress, which took place Jan. 29-Feb. 1 in Rio de Janeiro, per a press release from the biopharmaceutical.
“These data underscore seralutinib’s potential to transform the PAH treatment paradigm, if approved,” Faheem Hasnain, Gossamer’s cofounder, chairman, and CEO, said in an earlier press release announcing the company’s presence at the congress.
Gossamer last year entered into a collaboration and license agreement with the Chiesi Group to develop and potentially market seralutinib as a treatment for types of pulmonary hypertension.
Treatment found to improve blood flow in PAH
In PAH, the pulmonary arteries in the lungs become thick and narrow, causing high blood pressure in these blood vessels. This makes it hard for the heart to pump blood into the lungs, leading to symptoms like shortness of breath, persistent cough, and, over time, heart failure.
Seralutinib is designed to block the activity of certain signaling proteins that play roles in the abnormal cell growth that drives PAH.
In a Phase 2 study called TORREY (NCT04456998), inhaling seralutinib into the lungs twice daily in addition to standard-of-care treatment for PAH resulted in significantly lower pulmonary vascular resistance, or PVR — the resistance that must be overcome for blood to flow — compared with a placebo.
The TORREY study included 86 adults with PAH who were randomly assigned to receive either seralutinib or the placebo for 24 weeks, or about six months. After completing these six months, participants had the option to continue in an extension study (NCT04816604) in which all are being treated with seralutinib.
In addition to enrolling 73 of the 80 patients who completed TORREY, the extension study included one of the eight patients who completed an earlier Phase 1b study (NCT03926793) of seralutinib. Interim data from that study showed that treatment with seralutinib continued to be well tolerated for as long as 72 weeks, or nearly 1.5 years.
In a poster titled “Sustained Benefit with Seralutinib Treatment: A Post-Hoc Analysis of the TORREY Open-Label Extension,” the researchers provided an analysis of data from 28 patients who received seralutinib for 72 weeks — including the 24 weeks of the TORREY study. These patients had been diagnosed with PAH within a mean of 6.4 years, at an average age of 45.9.
During the extension study, PVR continued to improve in 20 of the 28 patients. A total of 17 were considered responders, meaning they achieved a reduction of more than 15% in their PVR from the start of TORREY. For responders, PVR was reduced by a median of 32%, ranging from 17% to 62%.
Over 72 weeks, mean pulmonary arterial pressure dropped by a median of 7.7% among all 28 patients, and more so, by 11.8%, among responders. Cardiac output, a measure of how much blood is pumped by the heart, increased by a median 1.8% among all patients. Among responders, it increased by a median of 19.6%.
These changes resulted in an increase in the distance covered walking for six minutes. There was an average increase of 29.8 meters (97.8 feet) among all 28 patients or 38.6 meters (126.6 feet) among responders, indicating better exercise capacity with seralutinib, which “was well tolerated, with no new safety signals.”
Trials build on results of preclinical studies of seralutinib
A separate poster, “Sustained Effect of Seralutinib on Circulating Biomarkers in the TORREY Phase 2 Open-Label Extension Study,” also detailed benefits seen with the therapy candidate. According to the researchers, there were “long-term biomarker changes [that] support a sustained effect of seralutinib on proteins and pathways relevant to PAH.”
These changes included an increase in the levels of interleukin-10, an anti-inflammatory protein that also helps to control how relaxed blood vessels are. This was seen in patients who switched from the placebo to seralutinib as they moved over into the extension study. For patients already on seralutinib, those levels were kept high.
The levels of another protein, collagen 1A1, which is elevated in fibrotic, or scar, tissue formed due to PAH, decreased in patients who switched from the placebo to seralutinib, per the data. For patients who continued on seralutinib, collagen 1A1 remained low during the extension study.
Gossamer Bio noted that these findings are supported by preclinical data. Those data showed that combining seralutinib with a molecule similar to sotatercept — the active ingredient in Winrevair, an approved PAH therapy — cuts off the production of profibrotic proteins by lab-grown cells from human lungs or hearts more so than the sotatercept analog alone.
In a rat model of PAH, the combination treatment also resulted in better blood flow into the lungs, as well as better heart function, than either treatment alone, “supporting the clinical potential” of combining seralutinib and sotatercept, the researchers wrote in a poster presenting these preclinical data.
According to Hasnain, “data from [these] preclinical models … provide evidence of a synergistic treatment effect from the combination of seralutinib and sotatercept.”
The researchers noted that both the ongoing extension study and PROSERA (NCT05934526), a global Phase 3 study that’s also underway, “allow for protocol-specified use of sotatercept and seralutinib.” PROSERA is now recruiting an estimated 350 PAH patients who will be randomly assigned to receive seralutinib or a placebo.
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