The IMPALA Phase 2/3 trial for Savara’s Molgradex inhaled molgramostim for the treatment of autoimmune pulmonary alveolar proteinosis (PAP) will be modified in order to qualify as a pivotal study for a US regulatory submission, the company said. According to Savara, the FDA has provided guidance on increasing enrollment and changing endpoint hierarchy and analysis that, if successful, would allow the company to use the trial as a pivotal study for the US as well as in Japan and Europe.
Patients enrolled in IMPALA will receive either a once-daily dose of Molgradex, Molgradex plus inhaled placebo in 7-day intermittent cycles, or once-daily placebo over a 24-week treatment period. The primary endpoint is absolute change from baseline in arterial-alveolar oxygen concentration. The FDA is expected to focus on several secondary endpoints: six-minute walk distance, St. George’s respiratory questionnaire, and the time to need for whole lung lavage.
In accordance with FDA guidance, enrollment in the study will be increased from 51 to 90. Savara says that the study has already enrolled half that number and that completion of enrollment is expected by the first quarter of 2018. The company anticipates the availability of top line data by the fourth quarter of 2018.
Savara CEO Rob Neville commented, “In the short time since we acquired Molgradex in July 2016 we have made tremendous progress, and having the opportunity to utilize our ongoing IMPALA study as a global Phase 3 study is a major win for the company, with the potential to considerably expedite the approval of the product in the US by eliminating the need to conduct a separate Phase 3 study. This is very good news for the PAP community in the US, as we believe Molgradex can offer a game changing treatment alternative in a disease where the current standard treatment option is to periodically conduct an invasive whole lung lavage procedure requiring general anesthesia.”
Read the Savara press release.