Seralutinib narrowly misses goal in PAH trial, but benefits seen for patients
Developer to seek talks with FDA on next steps for inhaled therapy
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People with pulmonary arterial hypertension (PAH) who were treated with the inhaled therapy seralutinib in a clinical trial tended to have better improvements in exercise capacity than those given a placebo, data show. However, the difference between the groups failed to meet a prespecified threshold for statistical significance.
That meant the Phase 3 trial narrowly missed its main goal, despite the benefits seen among treated patients — particularly those considered high risk.
According to Gossamer Bio, which is developing seralutinib in collaboration with the Chiesi Group, “all four key secondary endpoints [goals] favored seralutinib versus [the] placebo in the overall [patient] population.”
Gossamer announced the top-line results from the trial, dubbed PROSERA (NCT05934526), in a company press release that outlined the findings. The company said it now plans to meet with the U.S. Food and Drug Administration (FDA) to go over these data and discuss the further development of seralutinib for PAH.
“Given the significant unmet need in PAH, and seralutinib’s differentiated, nonvasodilatory mechanism, we believe these results warrant further discussions with the FDA regarding a potential path forward,” said Faheem Hasnain, Gossamer’s cofounder, CEO, and chairman. “We are deeply grateful to the patients, investigators, and clinical teams whose participation made this study possible.”
The PROSERA study enrolled 390 people with PAH. Participants were randomly assigned to receive either seralutinib or the placebo twice daily via inhalation for about a year.
Trial tested therapy’s impact via six-minute walk test results
The trial’s main goal was to assess the impact of treatment on the six-minute walk test (6MWT) after about six months. The 6MWT simply measures how far someone can walk in six minutes; it is commonly used to assess exercise capacity in people who can walk.
The results showed that patients given seralutinib had better 6MWT scores than those given the placebo, by about 13 meters (slightly longer than 40 feet) on average. But for the trial to meet its goal, this difference needed to be statistically significant — essentially meaning it’s highly unlikely the difference is due only to random chance.
Statistical significance is commonly measured using a so-called p-value. In most studies, a result is considered statistically significant if the p-value is less than 0.05, meaning there’s less than 5% chance the results are due to random chance. But the PROSERA study was designed so that a difference would only be considered significant with a p-value lower than 0.025 (2.5% chance of random results).
According to Gossamer, the difference between seralutinib and the placebo showed a p-value of 0.032, which does not reach that prespecified criteria for statistical significance. As such, the study did not reach its main goal.
“While we are disappointed to have narrowly missed the stringent prespecified statistical threshold for our primary endpoint, the result still clears the traditional 0.05 p-value, and we believe these data clearly demonstrate seralutinib is an active drug in patients with PAH,” Hasnain said.
From a clinical development perspective, this is not a narrow or exploratory finding. … Seralutinib has once again demonstrated a statistically robust and clinically meaningful signal in higher‑risk patients.
In a subset of 234 patients with intermediate- or high-risk disease at the start of the trial, 6MWD scores favored seralutinib over the placebo by 20 meters (66 feet). That difference was statistically significant with a p-value of 0.0207. Most secondary endpoints also showed a statistically significant effect favoring seralutinib in patients who were higher risk, according to Gossamer.
“From a clinical development perspective, this is not a narrow or exploratory finding,” Hasnain said, noting that people with intermediate- or high-risk PAH “are at an increased risk of significant morbidity and mortality events and represent a population with a high unmet need.”
According to Hasnain, the improvements seen among high-risk patients in PROSERA are comparable to the positive results seen in an earlier Phase 2 study called TORREY (NCT04456998).
“Seralutinib has once again demonstrated a statistically robust and clinically meaningful signal in higher‑risk patients, consistent with the TORREY Study, which is a clearly defined and readily identifiable population. This finding is compelling on its own,” Hasnain said. “Altogether, these data support the conclusion that seralutinib demonstrated greater activity in patients with more advanced disease. This is even more impressive given how heavily treated the PROSERA population was, including 55% of patients on triple or quadruple background PAH therapy and 61% on background prostacyclin therapy.”
Prostacyclin is a vasodilator, a medication that works to widen blood vessels.
PROSERA data show seralutinib was generally well tolerated
Safety data from PROSERA indicated seralutinib was generally well tolerated.
The overall rates of serious safety issues were comparable in participants given the therapy or the placebo, though patients given seralutinib more often showed elevations in liver damage markers. Gossamer also said that biomarker data indicated seralutinib reduced levels of NT‑proBNP, a marker of heart damage, relative to the placebo group.
Results from a functional respiratory imaging substudy are expected in the coming weeks. According to the company, they are expected “to provide additional insight into seralutinib’s treatment effect, including pulmonary blood volume distribution.”
Gossamer is also running a Phase 3 study called SERANATA (NCT07181382) that’s testing seralutinib in people with pulmonary hypertension associated with interstitial lung disease (PH-ILD). The company said enrollment in that study is being paused pending further analysis of data from PROSERA.
Specifically, the company noted concerns that patients at certain study sites, particularly in Latin America, as well as Asia/Middle East, often showed marked improvements despite being given the placebo, and this type of response wasn’t as pronounced at other sites.
