Trial in Progress: PROSERA, a Phase 3 Study of the Efficacy and Safety of Seralutinib in Adults with Pulmonary Arterial Hypertension (PAH)

Introduction Seralutinib is a highly potent inhibitor of PDGFRα/β, CSF1R, and c-KIT kinase pathways that activate inflammation, proliferation, and fibrosis, and drive vascular remodeling in PAH. Seralutinib is the first tyrosine kinase inhibitor specifically formulated for inhaled delivery to achieve deep lung deposition while minimizing systemic exposure. The phase 2 TORREY study of seralutinib in patients with PAH receiving standard of care (SOC) therapy met its primary endpoint, demonstrating a statistically significant reduction in pulmonary vascular resistance (PVR) compared to placebo, with favorable tolerability (NCT04456998). Significant improvements in N-terminal pro B-type natriuretic peptide (NT-proBNP) and right heart function by echocardiography were also observed.

Methods PROSERA is a global phase 3, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of inhaled seralutinib in adults with WHO Group 1 Pulmonary Hypertension, Functional Class (FC) II or III, PVR≥400 dyne·s/cm⁵, six-minute walk distance (6MWD) 150–475 m, either REVEAL Lite 2 Risk Score≥5 or NT-proBNP≥300 ng/L or PVR≥800 dyne·s/cm⁵, and on stable treatment with at least one SOC PAH background therapy, including parenteral prostacyclins (NCT05934526). A total of 350 patients will be enrolled and randomized to receive seralutinib 90 mg or placebo by dry powder inhaler twice daily for up to 48 weeks. The primary endpoint is change in 6MWD from baseline (BL) to Week 24. Key secondary endpoints (measured from BL) are time to first event of clinical worsening through Week 48, proportion of patients achieving clinical improvement (Week 24), change in NT-proBNP (Week 24), and proportion of patients with≥1 point decrease in REVEAL Lite 2 Risk Score (Week 24). Other secondary endpoints (measured from BL) include proportion of patients with each of the clinical worsening outcomes (through Week 48), proportion of patients who improve in WHO FC or maintain WHO FC II (through Week 48) and change in health-related quality of life (PAH-SYMPACT, EQ-5D-5L; Week 24). Patients who complete the study on blinded treatment may be eligible to enroll in a separate open-label extension study. A functional respiratory imaging sub-study will examine the effect of seralutinib on pulmonary vascular remodeling.

 

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Publication History

Article published online:
18 March 2025