Savara has announced that the Phase 3 IMPALA-2 trial of molgramostim nebulized recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with autoimmune pulmonary alveolar proteinosis (aPAP) met its primary endpoint, achieving statistically significant change in percent predicted diffusing capacity of the lungs for carbon monoxide (DLCO) compared to placebo at Week 24. A secondary endpoint, statistically significant difference in percent predicted DLCO compared to placebo at Week 48 was also met. Savara announced the initiation of the IMPALA-2 trial in June 2021.
The company said that molgramostim was well tolerated, with 97% of the patients completing the trial through 48 weeks and 100% of those patients choosing to continue in a 96-week open label extension. COVID-19 occurred more often in patients taking molgramostim than in those receiving placebo, 22% vs. 10%. Other adverse events occurred at similar rates between the two groups.
In June 2019, Savara announced that the first IMPALA study of molgramostim (Molgradex) for aPAP had failed to meet its primary endpoint but that it had demonstrated statistically significant improvement on some secondary endpoints. Later that year, the FDA issued a letter discouraging a BLA submission for molgramostim for aPAP based on the data available at that time. According to the new announcement, the company now intends to complete the BLA submission for molgramostim in the first half of 2025.
The FDA has granted molgramostim orphan drug, Fast Track, and Breakthrough Therapy designations for the treatment of aPAP. Molgramostim has also received Innovative Passport and Promising Innovative Medicine designations from the UK MHRA and orphan drug designation from the EMA for that indication.
Savara Chair and CEO Matt Pauls commented, “The IMPALA-2 results not only met, but exceeded, our expectations, validating our hypothesis that molgramostim provides clear, durable improvement in gas exchange, and beyond that, clinical benefits that positively impact quality of life for aPAP patients. The strong efficacy data and favorable benefit-risk profile potentially position molgramostim to be the first and only approved therapeutic for aPAP in the US and Europe. We extend our gratitude to the patients and their families, clinicians, and site personnel for their contributions and ongoing participation in the largest clinical trial in aPAP. We look forward to analyzing the full data from IMPALA-2 and anticipate submitting it for presentation at a scientific conference later this year.”
Read the Savara press release.
