Gossamer Bio (NASDAQ:GOSS) reported top-line results from PROSERA, its global phase III registrational study evaluating inhaled seralutinib in patients with pulmonary arterial hypertension (PAH). Company executives said the trial showed numerical improvement versus placebo on the primary endpoint but did not meet the study’s pre-specified statistical threshold, which management attributed largely to an unexpectedly strong placebo response and regional heterogeneity.
Primary endpoint missed despite numerical benefit
PROSERA was a randomized, double-blind, placebo-controlled phase III study in WHO Functional Class II and III PAH patients on background therapy. The trial randomized 390 patients 1:1 to seralutinib (n=197) or placebo (n=193) and treated patients for up to 48 weeks.
Management emphasized that while p=0.032 is below the commonly cited 0.05 benchmark, it did not meet PROSERA’s pre-specified two-sided alpha of 0.025; as a result, the trial is considered not statistically significant on the primary endpoint.
Placebo response and regional variability cited as key factors
Executives described the placebo response as “outsized” and said it was higher than what is typically seen in PAH trials, which compressed the placebo-adjusted treatment effect. The company also pointed to meaningful regional heterogeneity.
According to management, placebo performance in North America was more consistent with “typical modern PH trials,” and the treatment effect was most pronounced there, with a 25.9-meter placebo-adjusted improvement in 6MWD. In contrast, the company said Latin America showed particularly large placebo improvements, which materially reduced the pooled treatment difference.
Gossamer added that it observed “super responders” on placebo in Latin America, including patients with more than 100-meter improvements in walk distance, and said it plans to further investigate the drivers of the regional placebo effect with investigators and its clinical research partners.
Pre-specified higher-risk subgroup showed larger separation
Management highlighted results in a pre-specified intermediate- and high-risk subgroup defined by a REVEAL Lite 2 risk score of at least 6 (234 patients, roughly two-thirds of the PROSERA population). In that subgroup, seralutinib demonstrated a 20-meter placebo-adjusted improvement in 6MWD at week 24, with a p-value of 0.0207.
Company representatives stressed that this was not a post-hoc analysis, noting that the subgroup was pre-specified and clinically relevant. They also explained on the call that REVEAL Lite 2 ≥5 was used as an enrollment criterion agreed with the FDA, while the ≥6 cut reflected the median risk score in the enrolled population and was used in the prespecified subgroup analysis.
Across key secondary endpoints, management said results “consistently favored” seralutinib, including time to clinical worsening, NT-proBNP, clinical improvement, and REVEAL Lite 2 risk score reduction, while noting that p-values discussed for endpoints other than the primary endpoint were nominal. In the overall population, NT-proBNP at week 24 showed an estimated location shift of negative 124 ng/L versus placebo with a nominal p-value of 0.002, with separation observed as early as week 4. In the intermediate/high-risk subgroup, the company reported a larger NT-proBNP reduction of approximately 266 ng/L and said patients treated with seralutinib were over three times more likely to improve compared to placebo.
On time to clinical worsening, management said the endpoint was important, but the number of events was low (39 events by week 24), limiting statistical power.
Additional observations: CTD subgroup, sotatercept background, and 48-week data
Executives also referenced “compelling results” in certain subgroups. They said patients with PAH associated with connective tissue disease (CTD) were the top performer in PROSERA, with a 37-meter placebo-adjusted improvement in 6MWD, and linked the outcome to seralutinib’s anti-inflammatory and anti-fibrotic mechanism of action.
In addition, management discussed results in the small number of patients on background sotatercept in the trial, stating there were six such patients (five on seralutinib and one on placebo). Those on seralutinib had a mean improvement of over 70 meters, which the company said was consistent with preclinical expectations of synergy, while cautioning that the dataset was limited.
On longer-term outcomes, the company said patients who remained in PROSERA through week 48 continued to improve and that curves appeared to separate further over time, while acknowledging the limited sample size at week 48 due to rollover into an open-label extension and withdrawals. In response to a question, management characterized the week 48 analysis as showing roughly a 30-meter improvement and cited a p-value of 0.02 using an ANCOVA approach without imputations.
Safety profile and next steps
Gossamer said seralutinib was generally well tolerated and that the safety profile was consistent with prior experience. Treatment-emergent adverse events were reported in 86.5% of seralutinib patients and 80.5% of placebo patients, with similar rates of severe adverse events. Serious adverse events occurred in 16.0% of seralutinib patients and 18.9% of placebo patients, and deaths were similar between groups.
The most frequent adverse event on seralutinib was cough (37% vs. 13.7% placebo). ALT and AST increases were higher on seralutinib (14.5% and 14.0%, respectively) versus 0.5% for each on placebo. The company reported liver transaminase elevations of at least three times the upper limit of normal in 13% of seralutinib patients and 1% of placebo patients, typically occurring in the first three months and resolving after drug interruption or discontinuation.
Following the PROSERA outcome, management outlined three priorities: fully understanding the dataset, engaging with the FDA, and evaluating strategic options and resource allocation. The company also said it will pause enrollment in the SERANATA phase III study to prioritize resources toward the Group 1 PAH opportunity and to incorporate learnings from PROSERA, while stating the pause does not reflect reduced belief in seralutinib’s potential in fibrotic disease.
On timing, executives said they anticipate results from the FRI lung imaging study—assessing blood volume distribution in the lungs—early in the second quarter and described it as potentially important context for interpreting PROSERA and supporting regulatory discussions.
On financials, management said it expects to end the first quarter with roughly $105 million in cash, and said it is evaluating runway and timing for regulatory interactions. The company also addressed future debt obligations and said it plans to engage with stakeholders on options, while noting that partner Chiesi remains supportive of the program.
About Gossamer Bio (NASDAQ:GOSS)
Gossamer Bio, Inc is a clinical-stage biopharmaceutical company headquartered in San Diego, California. Founded in 2012, the company is focused on discovering and developing oral, once-daily therapies for immune-mediated and inflammatory diseases, as well as oncology indications. Gossamer Bio leverages a deep pipeline of small-molecule candidates aimed at improving patient outcomes in areas of high unmet need.
The company’s lead programs include GB004, an S1P1 receptor modulator in late-stage development for ulcerative colitis, and GB1275, a CD11b modulator being investigated in solid tumors and hematologic malignancies.
