Savara Inc. announced topline data from the pivotal phase 3 trial, IMPALA, which evaluated Molgradex (molgramostim) for the treatment of autoimmune alveolar pulmonary proteinosis (aPAP), a rare lung disease characterized by the accumulation of surfactant in the airways.
The safety and efficacy of Molgradex, an inhaled formulation of recombinant human granulocyte macrophage colony stimulating factor (GM-CSF), was evaluated in a double blind, placebo controlled trial involving 138 patients with aPAP. Patients were randomized to receive 1 of 3 treatments for 24 weeks: Molgradex 300µg once daily continuously, Molgradex 300µg once daily in 7-day intermittent cycles with placebo, or inhaled placebo once daily continuously. The primary endpoint was the absolute change from baseline to 24 weeks of alveolar – arterial oxygen gradient (A-aDO2); key secondary endpoints were change from baseline in St. George’s Respiratory Questionnaire (SGRQ) total score (a patient-related outcomes/quality-of-life measure) and 6-minute walk distance (6MWD); as well as time to whole lung lavage (WLL).
Results showed that the study did not meet its primary endpoint with an estimated A-aDO2 treatment difference of 4.6 mmHg between the Molgradex continuous dosing and placebo arms (12.1 mmHg vs 8.8 mmHg, respectively; P =.17). However, the study showed a statistically significant improvement in the SGRQ score in the continuous dosing arm compared with placebo (12.3 points vs 4.7 points, respectively; P =.01). With regard to both 6MWD and WLL, the differences observed between the continuous dosing and placebo arms were found not to be statistically significant.
“Disappointingly, with the placebo effect stronger than anticipated, the study did not meet its primary endpoint,” said Rob Neville, Chief Executive Officer of Savara. “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.”
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