At a Glance
- PROSERA Phase 3 trial of inhaled seralutinib in 390 PAH patients narrowly missed the primary 6MWD endpoint (p=0.0320 > α=0.025).
- Strong signals emerged in high-risk subgroup with +20m 6MWD gain (p=0.0207) and three of four key secondary endpoints meeting p<0.0125.
- NT-proBNP biomarker improved significantly (-120.4 ng/L overall, p=0.0002), especially in advanced patients on triple/quadruple therapy.
- Seralutinib well-tolerated overall with manageable safety profile despite higher cough and transaminase elevations versus placebo.
Written By: Sana Khan, BPharm
Reviewed By: Pharmacally Editorial Team
Gossamer Bio, Inc., a biopharmaceutical company developing seralutinib for pulmonary arterial hypertension (PAH) and pulmonary hypertension associated with interstitial lung disease (PH-ILD), announced topline results from the PROSERA Phase 3 trial (NCT05934526).
The study evaluated seralutinib, an inhaled tyrosine kinase inhibitor targeting platelet-derived growth factor receptor (PDGFR), colony-stimulating factor 1 receptor (CSF1R), and proto-oncogene c-KIT (c-KIT) to address inflammation, proliferation, and fibrosis in PAH.
Primary Endpoint Results
The primary endpoint measured the median change in 6-minute walk distance (6MWD) a standard test where patients walk as far as possible in six minutes to assess exercise capacity and daily function. Patients on seralutinib improved by a median of +28.2 meters at Week 24 from baseline, versus +13.5 meters for placebo. The Hodges-Lehmann treatment effect a statistical method estimating the median difference between treatments showed a +13.3-meter placebo-adjusted gain (p=0.0320), but this narrowly missed the study’s strict prespecified threshold (α=0.025) for statistical significance.
Risk Stratification Tool
The REVEAL 2 Lite Risk Score is a validated tool that predicts PAH patient outcomes based on factors like symptoms, walk distance, and biomarkers; scores ≥6 indicate intermediate- or high-risk patients with worse prognosis and higher unmet need.
Strong Signals in High-Risk Subgroups
In the prespecified intermediate- and high-risk subgroup (REVEAL 2 Lite Risk Score ≥6 at screening, n=234), seralutinib showed a +20.0 meter placebo-adjusted 6MWD improvement (p=0.0207). Three of four key secondary endpoints met strict significance levels (p<0.0125), aligning with Phase 2 TORREY (NCT04456998) results and highlighting benefits in advanced, heavily treated patients (55% on triple/quadruple therapy, 61% on prostacyclin).
Key Secondary Endpoints
NT-proBNP a blood biomarker reflecting heart strain that rises with PAH severity dropped by -120.4 ng/L versus placebo at Week 24 (p=0.0002) in the overall population, with benefits visible from Week 4. Other endpoints, including time-to-clinical worsening (e.g., death, hospitalization, or therapy escalation), clinical improvement (symptom and function gains), and ≥1-point REVEAL Lite 2 risk score reduction (signifying better prognosis), all numerically favored seralutinib.
In high-risk patients, NT-proBNP fell further (-265.8 ng/L; p=0.0002), with odds ratios of 2.033 for risk score improvement (p=0.0083) and 3.318 for clinical improvement (p=0.0101).
Subgroup Highlights
Seralutinib delivered a +37.0 meter placebo-adjusted 6MWD gain in connective tissue disease-associated PAH (CTD-PAH, n=87; p=0.0104). These results underscore activity in challenging populations despite heavy prior treatments.
Safety Profile
Seralutinib was generally well-tolerated, with treatment-emergent adverse events in 86.5% (seralutinib) versus 80.5% (placebo). Serious adverse events occurred in 16.0% versus 18.9%. Cough was most common (37.0%), and transaminase elevations ≥3x upper limit affected 13% on seralutinib versus 1% on placebo.
Study Design and Next Steps
PROSERA enrolled 390 WHO Functional Class II/III PAH patients (197 seralutinib, 193 placebo) on background therapy, randomized double-blind for up to 48 weeks. Gossamer plans FDA discussions on a path forward and has paused SERANATA enrollment for evaluation. Upcoming CT functional respiratory imaging sub study results may add insights into pulmonary effects.
Reference
Gossamer Bio Announces Topline Results from the Phase 3 PROSERA Study Evaluating Seralutinib in Pulmonary Arterial Hypertension, 23 February 2026, Gossamer Bio Announces Topline Results from the Phase 3 PROSERA Study Evaluating Seralutinib in Pulmonary Arterial Hypertension | Gossamer Bio
Efficacy and Safety of Seralutinib in Adult Subjects with PAH (PROSERA), ClinicalTrials.gov ID NCT05934526, https://clinicaltrials.gov/study/NCT05934526
GB002 in Adult Subjects with Pulmonary Arterial Hypertension (PAH), ClinicalTrials.gov ID NCT04456998, https://clinicaltrials.gov/study/NCT04456998