Savara's Molgramostim Nebulizer Solution Meets Primary and Secondary Endpoints in Phase 3 IMPALA-2 Trial

Savara Inc., a clinical-stage biopharmaceutical company focused on rare respiratory diseases, has announced positive results from its pivotal Phase 3 IMPALA-2 clinical trial. The trial evaluated the efficacy and safety of molgramostim, an inhaled form of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF), in adult patients with autoimmune pulmonary alveolar proteinosis (aPAP).

The 48-week randomized, double-blind, placebo-controlled trial included 164 participants (NCT04544293). Molgramostim was administered once daily by inhalation at a dose of 300 mcg, while a matching placebo was used for comparison. The primary endpoint of the trial was the percent predicted diffusing capacity of the lungs for carbon monoxide (DLCO), adjusted for hemoglobin levels. Secondary endpoints included the St. George’s Respiratory Questionnaire (SGRQ) Total Score, SGRQ Activity Score, and exercise capacity measured by a treadmill test.

Key findings from the trial revealed that molgramostim led to statistically significant improvements in the primary endpoint of DLCO at both Week 24 and Week 48. Specifically, at Week 24, the mean change from baseline was 6.00 with a p-value of 0.0007, and at Week 48, the mean change was 6.90 with a p-value of 0.0008. These results indicate a durable effect of the treatment.

In terms of secondary outcomes, the SGRQ Total Score showed a statistically significant improvement at Week 24, with a mean change of -6.59 points and a p-value of 0.0072. Although the SGRQ Total Score at Week 48 did not reach statistical significance, it still demonstrated positive trends. The SGRQ Activity Score at Week 24 also achieved nominal significance, whereas the treadmill test for exercise capacity showed a significant improvement at Week 48 with a p-value of 0.0234.

The safety profile of molgramostim was favorable, with 97% of patients completing the double-blind treatment through Week 48 and no trial drug-related adverse events leading to discontinuation. The most common adverse events reported in the molgramostim group were COVID-19, cough, and pyrexia. Importantly, 100% of the patients who completed the 48-week double-blind period chose to continue into the 96-week open-label period.

Bruce Trapnell, M.D., the Lead Clinical Investigator of the IMPALA-2 trial, emphasized the substantial unmet need for effective pharmacotherapy in aPAP. He highlighted the potential of molgramostim as a safe and efficacious treatment option, supported by compelling data from two large clinical trials. Matt Pauls, Chair and CEO of Savara, echoed this sentiment, noting the strong efficacy data and favorable benefit-risk profile of molgramostim. He expressed optimism that molgramostim may become the first approved therapeutic for aPAP in the U.S. and Europe.

The positive results from the IMPALA-2 trial have significant implications for the treatment of aPAP, a rare lung disease characterized by the abnormal accumulation of surfactant in the alveoli. This buildup inhibits gas exchange and can lead to symptoms such as shortness of breath, cough, and fatigue. Over time, the disease can cause serious complications, including lung fibrosis and the need for lung transplantation.

Savara plans to complete the submission of a Biologics License Application (BLA) for molgramostim in the first half of 2025. The company will also host a webcast conference call to discuss the IMPALA-2 results and future plans. With Orphan Drug, Fast Track, and Breakthrough Therapy designations from the U.S. Food and Drug Administration and similar recognitions from European and UK regulatory bodies, molgramostim is positioned as a promising candidate for addressing the unmet needs of aPAP patients.

In summary, the IMPALA-2 trial has demonstrated that molgramostim provides significant and durable improvements in lung function for patients with aPAP, with a manageable safety profile, paving the way for its potential approval and use as a targeted therapy in this rare respiratory disease.