PROSERA Phase 3 Topline Results and Regulatory Next Steps for Seralutinib

Gossamer Bio reports topline Phase 3 results for inhaled seralutinib in pulmonary arterial hypertension (PAH) from the PROSERA study. The company states the trial did not meet the primary endpoint’s threshold for declaring success and describes subsequent efficacy readouts as nominal rather than formally confirmatory.

In the company’s description, PROSERA enrolled 390 patients with WHO Functional Class II or III PAH and randomized 197 patients to seralutinib and 193 to placebo. Background therapy was common: 55% of enrolled patients received triple or quadruple PAH therapy and 61% received background prostacyclin therapy, with treatment arms described as generally well balanced at baseline.

The prespecified primary endpoint was change from baseline in 6-minute walk distance (6MWD) at Week 24. The release reports an estimated placebo-adjusted Hodges‑Lehmann treatment effect of +13.3 meters with a p value of 0.0320 and states this did not meet the prespecified α=0.025 threshold for the primary endpoint. On that basis, the company states that p values for key secondary endpoints cannot be evaluated for statistical significance and that all p values reported are nominal. As presented, the primary endpoint result is reported as numerically favoring seralutinib without crossing the prespecified statistical boundary.

The release highlights a prespecified intermediate- and high-risk subgroup defined as REVEAL 2 Lite Risk Score ≥6 at screening (n=234), reporting a placebo-adjusted 6MWD improvement of +20.0 meters with p=0.0207. It also states that three of four key secondary endpoints had p values below 0.0125 in this subgroup and provides selected subgroup effect estimates for some endpoints. For the biomarker endpoint NT‑proBNP at Week 24, the company reports an estimated location shift of −120.4 ng/L versus placebo in the overall population (p=0.0002) and −265.8 ng/L in the higher-risk subgroup (p=0.0002). The company also reports a connective tissue disease–associated PAH subgroup analysis (n=87) with a placebo-adjusted 6MWD gain of +37.0 meters at Week 24 (p=0.0104), characterizing these as subgroup and secondary signals observed within the nominal framework.

On safety and tolerability, treatment-emergent adverse events occured in 86.5% of seralutinib-treated patients versus 80.5% with placebo and serious adverse events in 16.0% versus 18.9%, respectively. It also reports transaminase elevations ≥3× the upper limit of normal in 13% versus 1% and identifies cough as the most frequently reported adverse event with seralutinib (37.0%).

Operationally, the company states it expects to meet with the U.S. Food and Drug Administration to discuss next steps and that it is pausing enrollment in the ongoing SERANATA study while evaluating PROSERA results, citing regional discrepancies in placebo response. The release adds that CT functional respiratory imaging substudy results are expected in the coming weeks and are expected by the company to provide additional insight, including pulmonary blood volume distribution, positioning these pending analyses alongside the safety and operational updates as the near-term readout context.

Key Takeaways:

• PROSERA did not meet the prespecified primary endpoint threshold for 6MWD and treats reported p values as nominal under the analysis plan.
• Prespecified higher-risk and other subgroup analyses, along with NT‑proBNP changes, were reported as signals separating seralutinib from placebo.
• The press release describes safety findings (including liver-enzyme elevations and cough) and operational/regulatory steps (FDA discussion plans, SERANATA enrollment pause, and pending FRI substudy results).