Gossamer Bio saw its shares collapse by roughly 80% on Monday after its lead candidate seralutinib failed to achieve the primary efficacy goal in the Phase 3 PROSERA trial for pulmonary arterial hypertension (PAH).
In PROSERA, seralutinib produced a placebo-adjusted improvement in Six-Minute Walk Distance (6MWD) of 13.3 meters at Week 24, with a reported p-value of 0.0320. That outcome did not meet the trial's prespecified alpha threshold of 0.025, leaving the primary endpoint formally unmet despite a measurable difference versus placebo. Median changes from baseline were 28.2 meters for patients receiving seralutinib and 13.5 meters for those on placebo.
Not all analyses were uniformly negative. In a prespecified intermediate and high-risk subgroup comprising 234 patients, seralutinib achieved a larger placebo-adjusted 6MWD improvement of 20.0 meters with a p-value of 0.0207. The treatment effect was most marked in the North American cohort, where the placebo-adjusted improvement reached 25.9 meters; however, that regional difference did not attain statistical significance within the overall trial framework.
A predefined secondary endpoint also favored seralutinib. At Week 24 the drug reduced NT-proBNP, a circulating biomarker associated with cardiac stress, by 120.4 ng/L relative to placebo. In the subgroup of patients whose PAH was associated with connective tissue disease, the treatment produced a placebo-adjusted gain of 37.0 meters in 6MWD.
On safety, seralutinib was generally tolerated but was associated with treatment-emergent adverse events in 86.5% of treated patients versus 80.5% in the placebo arm. The most commonly reported adverse event was cough, occurring in 37.0% of patients who received seralutinib.
In response to the PROSERA readout, Gossamer Bio said it will meet with the U.S. Food and Drug Administration to discuss next steps for seralutinib. The company has paused enrollment in its SERANATA study while it evaluates the PROSERA results, with particular focus on regional differences in placebo response that emerged in the data.
The PROSERA trial population included a high level of background therapy: 55% of participants were on triple or quadruple background PAH therapy, and 61% were receiving background prostacyclin therapy. Those characteristics are part of the dataset Gossamer intends to review with regulators as it charts a path forward.
Investors responded sharply to the missed primary endpoint, reflecting the market's sensitivity to late-stage clinical outcomes for a company whose valuation depends heavily on the success of a single development program. Gossamer's regulatory engagement and the pause to further enrollment underscore the uncertainty the company and its stakeholders now face as they interpret subgroup signals, secondary biomarker effects, and regional variability within the trial.