Savara has announced the initiation of the Phase 3 IMPALA-2 clinical trial of molgramostim inhaled recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment of autoimmune pulmonary alveolar proteinosis (aPAP). In December 2020, the company stopped development of the AeroVanc vancomycin DPI and Apulmiq (Linhaliq) inhaled liposomal ciprofloxacin and said that it would focus on molgramostim for aPAP. Development of molgramostim for the treatment of nontuberculous mycobacterial (NTM) lung infection had already been halted.
The original Phase 3 IMPALA study of Molgradex for aPAP failed to meet its primary endpoint but demonstrated statistically significant improvement on several secondary endpoints. In October 2019, the FDA issued a letter discouraging a BLA submission for molgramostim for aPAP due to insufficient data supporting its efficacy and safety; two months later, the FDA granted molgramostim Breakthrough Therapy designation for that indication.
IMPALA-2 is expected to enroll approximately 160 aPAP patients who will get either 300 µg of nebulized molgramostim or placebo once daily over 48 weeks. After the first 48-week double-blind study period, patients will enter an open label study period and will get 300 µg of nebulized molgramostim for an additional 48 weeks.
Savara Chief Medical Officer Badrul Chowdhury commented, “With the first patient dosed in IMPALA-2, we hit a critical milestone in-line with our guidance for the trial. Our highest priority is to continue activating sites and working with the global aPAP community to enroll patients. Data from the IMPALA trial gave us confidence that molgramostim has the potential to address a significant unmet need in aPAP and we look forward to building on those supportive data to advance the development of molgramostim as the first potential pharmacological treatment for this debilitating disease.”
Read the Savara press release.
