Inhaled drug developer Savara has announced that the Phase 3 IMPALA study of Molgradex inhaled formulation recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment of autoimmune pulmonary alveolar proteinosis (aPAP) failed to meet its primary endpoint, improvement in alveolar-arterial oxygen gradient (A-aDO2).
The study enrolled 138 patients who received either a 300 µg dose of Molgradex once daily continuously for 24 weeks; a 300 µg dose of Molgradex alternated with inhaled placebo in 7-day cycles over the 24 weeks; or inhaled placebo only. Improvement in A-aDO2 for the continuous treatment arm was 12.1 mmHg, a 4.6 mmHg difference from the placebo arm, which was not sufficient to meet the primary endpoint.
Of several secondary endpoints, the differences in patient reported quality of life (as measured by SGRQ) and diffusing capacity of the lungs for carbon monoxide (DLCO) for the continuous treatment compared to placebo were statistically significant. Compared to placebo, improvements in 6-minute walk and requirement for whole lung lavage were not statistically significant
Savara CEO Rob Neville commented, “Disappointingly, with the placebo effect stronger than anticipated, the study did not meet its primary endpoint. However, we remain encouraged about the results of IMPALA, most notably the significant improvement in SGRQ, the consistency of trends and improvements seen across the endpoints and the favorable safety profile. We are preparing to meet with the FDA and EMA to discuss the results from this study and to determine our options to seek approval based on the current data, and potentially conduct an additional study incorporating the learnings from IMPALA. It is with much gratitude that we acknowledge the patients participating in the study. It is on their behalf that we will continue to pursue our goal of bringing this important therapy to market.”
Lead Investigator Bruce Trapnell of the University of Cincinnati College of Medicine said, “Taken together, the trends in reduction of A-aDO2,as well as the improvement in the diffusion capacity, are very consistent with reduction of the surfactant burden that causes the clinical symptoms of aPAP. Most importantly, the impressive improvement in quality of life, as measured by the SGRQ, suggest that Molgradex not only improved objective measures of oxygenation, but also had a clinically meaningful therapeutic effect. I believe these data demonstrate that Molgradex can become an important pharmacological treatment option for patients with aPAP.”
Savara is also developing Molgradex for the treatment of nontuberculous mycobacterial (NTM) lung infection in cystic fibrosis patients and announced the initiation of a Phase 2a trial for that indication earlier this year.
Read the Savara press release.
