Savara Inc. (Nasdaq: SVRA) announced new data from its pivotal Phase 3 IMPALA-2 trial, revealing sustained benefits of molgramostim in patients with autoimmune Pulmonary Alveolar Proteinosis (aPAP). The data, presented at the European Respiratory Society (ERS) Congress 2024 in Vienna, Austria, highlighted significant improvements in disease severity and lung function, reinforcing molgramostim's potential as a treatment for this rare respiratory condition.
The IMPALA-2 trial, a global, randomized, double-blind, placebo-controlled study, evaluated the efficacy and safety of molgramostim 300 mcg self-administered once daily by inhalation. The trial involved 48 weeks of treatment, with a primary endpoint assessing the change from baseline in hemoglobin-adjusted percent predicted diffusing capacity of the lungs for carbon monoxide (DLCO%) at Week 24. A key secondary endpoint measured the change from baseline to Week 48 in percent predicted DLCO% to evaluate the durability of the treatment effect.
Key Findings from IMPALA-2
The IMPALA-2 trial met its primary endpoint, demonstrating a statistically significant improvement in DLCO% at Week 24. This improvement was sustained through Week 48, indicating the durability of molgramostim's effect. Additional secondary endpoints also showed significant improvements, including the St. George’s Respiratory Questionnaire (SGRQ) Total Score at Week 24.
Further analyses presented at the ERS Congress provided additional insights into the benefits of molgramostim:
- Disease Severity Score (DSS): Significant improvements were observed in DSS at Weeks 24 and 48 in patients treated with molgramostim compared to placebo.
- DLCO% Responder Analysis: A significantly higher proportion of patients achieved clinically meaningful improvements in DLCO% (≥ 5, 7, and 10 percentage points) at Weeks 24 and 48 with molgramostim.
- SGRQ Total Score Responder Analysis: Numerically (at Week 24) and significantly (at Week 48) higher proportions of patients achieved responder thresholds (≥ 4, 8, and 12-point improvements) with molgramostim.
- Ground Glass Opacification (GGO) Score: Molgramostim significantly improved GGO score, a measure of surfactant burden, at Week 24.
Expert Commentary
Bruce Trapnell, M.D., Professor of Medicine and Pediatrics at the University of Cincinnati College of Medicine and the Lead Clinical Investigator of the IMPALA-2 trial, commented on the results: “The IMPALA-2 results demonstrate molgramostim’s ability to correct the pathobiology causing aPAP lung disease and improve its cardinal manifestations. Specifically, molgramostim reduced surfactant burden, increased pulmonary gas transfer, improved health-related quality of life, increased exercise capacity, and was well-tolerated in patients with aPAP.”
Regulatory Pathway
Savara plans to complete the submission of the Biologics License Application (BLA) for molgramostim in aPAP in the first half of 2025. Molgramostim has been granted Orphan Drug, Fast Track, and Breakthrough Therapy designations from the U.S. Food and Drug Administration (FDA), Orphan Drug designation from the European Medicines Agency (EMA), and Innovative Passport and Promising Innovative Medicine designation from the UK's Medicines and Healthcare Products Regulatory Agency (MHRA) for the treatment of aPAP.
About Autoimmune Pulmonary Alveolar Proteinosis (aPAP)
Autoimmune PAP is a rare lung disease characterized by the abnormal accumulation of surfactant in the alveoli of the lungs. This build-up impairs gas exchange, leading to symptoms such as shortness of breath, cough, and fatigue. In a healthy lung, alveolar macrophages clear excess surfactant, a process stimulated by granulocyte-macrophage colony-stimulating factor (GM-CSF). In aPAP, antibodies neutralize GM-CSF, preventing macrophages from clearing surfactant effectively.
