Site activation ahead of schedule for Phase 3 trial of seralutinib for PAH
PROSERA global study locations now expected to open by end of year
The activation of clinical sites for a global Phase 3 study to evaluate Gossamer Bio’s inhaled seralutinib (GB002), an investigational treatment for pulmonary arterial hypertension (PAH), is proceeding ahead of schedule.
Clinical locations in the study, dubbed PROSERA (NCT059345260), are expected to open by the end of the year in North America, Latin America, Europe, and the Asia Pacific region, with dosing to begin soon after.
“We are pleased with the progress our team has made with the launch of the seralutinib Phase 3 PROSERA study,” Faheem Hasnain, Gossamer Bio’s chairman, co-founder, and CEO, said in a company press release. “With sites opening up across the globe, we are hearing incredible enthusiasm and interest from investigators, patients and patient advocates, alike.”
Meanwhile, results from a CT imaging sub-study conducted during the previous Phase 2 TORREY trial showed six months of seralutinib increased the amount of blood flowing through the pulmonary arteries compared with a placebo. These blood vessels, which supply the lungs, are narrowed in people with PAH, causing restricted blood flow and high blood pressure.
Seralutinib seen to improve artery blood flow in TORREY study
Seralutinib, inhaled directly into the lungs, is designed to block the activity of selected signaling proteins involved in the abnormal cell growth that narrows the pulmonary arteries and drives PAH. In preclinical studies, the investigational therapy showed promise in two animal models of severe PAH.
The Phase 2 TORREY trial (NCT04456998) evaluated six months of seralutinib against a placebo in 86 people with PAH. Data showed that seralutinib treatment significantly lowered pulmonary vascular resistance (PVR), or the resistance against blood flow, by 14.3% compared with the placebo.
All participants who completed the study were invited to join its open-label extension (OLE) to receive treatment and assess long-term outcomes. The results from the ongoing OLE are expected to be reported by the end of the year, the company said.
Data from the TORREY imaging sub-study were recently presented at the European Respiratory Society International Congress 2023 by Roham T. Zamanian, MD, professor of pulmonary and critical care medicine at Stanford University, in California.
A total of 19 participants — seven given seralutinib and 12 the placebo — underwent CT scans of the lungs before and after the 24-week study period. With these scans, the volume of the pulmonary arteries, defined by their cross-sectional area or CSA, can be measured directly.
In PAH, the tiny pulmonary arteries farthest from the heart, with a CSA of less than 5 mm2 (BV5A), are narrowed. As a result, the broader vessels — with a CSA between 5-10 mm2 (BV5-10A) — that supply these tiny vessels become enlarged. As such, the ratio of BV5A to BV5-10A is lower in PAH than in healthy blood vessels.
After six months, the mean BV5A to BV5-10A ratio significantly increased in patients who received seralutinib, meaning more tiny vessels were wider, allowing for improved blood flow. Among the seralutinib-treated individuals, all but one (six patients) showed higher ratio values.
In the placebo group, there was no mean change in this measure and half, or six of the patients, had increased BV5A/BV5-10A ratios.
Higher BV5A/BV5-10A values also significantly correlated with improved measures of blood flow. This included stroke volume, the volume of blood pumped out of the heart, and pulmonary artery compliance, or the ability to distend and change volume in response to blood pressure changes.
These data provide encouraging clinical evidence of seralutinib’s ability to improve the pulmonary arterial blood vessel volume distribution for patients treated with seralutinib, as compared to placebo.
Zamanian presented CT images from two participants before and after the study. One seralutinib-treated patient had BV5A/BV5-10A increase by 78% and PVR drop by 39%. In comparison, a patient who received the placebo saw this ratio drop by 28.9%, and PVR increase by 65.4%.
“We were excited to have presented the results from the Phase 2 TORREY lung imaging sub-study” at the congress, Hasnain said.
“These data provide encouraging clinical evidence of seralutinib’s ability to improve the pulmonary arterial blood vessel volume distribution for patients treated with seralutinib, as compared to placebo, and are supportive of the growing body of preclinical evidence showing the effect of seralutinib on reverse remodeling,” Hasnain said.
According to the release, Gossamer is expecting the first patient in PROSERA to be dosed in the fourth quarter of this year. The trial’s primary endpoint, or goal, is a positive change in results on the six-minute walk distance ability test.