Savara Inc (NASDAQ:SVRA) announced that it has received guidance from the FDA on the clinical program requirements for a New Drug Application submission in the U.S. for Molgradex, an inhaled formulation of recombinant human GM-CSF, for the treatment of autoimmune pulmonary alveolar proteinosis, or PAP. Based on the FDA’s guidance, Savara will modify the endpoint hierarchy and statistical analyses of its ongoing IMPALA study, currently enrolling patients in Europe and Japan, to qualify the study as a pivotal Phase 3 study in the U.S. The total number of patients to be enrolled will be increased from 51 to 90 to support the modified design. If successful, the amended study would serve as the sole pivotal study for regulatory submission for marketing authorization of Molgradex for the treatment of PAP in the U.S. in addition to Europe and Japan.

“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 U.S. by eliminating the need to conduct a separate Phase 3 study,” stated Rob Neville, Chief Executive Officer of Savara. “This is very good news for the PAP community in the U.S., 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.”

The IMPALA study is a randomized, double-blind, placebo-controlled study designed to compare the efficacy and safety of Molgradex with placebo in patients with PAP. The study, which began enrolling patients in Europe and Japan last year, will be expanded to enroll a total of 90 patients, half of which have already been enrolled. Patient enrollment is expected to be completed by the first quarter of 2018, and top line data is expected to be available by the fourth quarter of 2018.

“Molgradex is a unique product that directly addresses the disease mechanism causing PAP – an autoimmune blockade of a naturally occurring signaling protein, GM-CSF, which is required to clear excess surfactant from the lungs,” said Dr. Bruce Trapnell, M.D., Professor of Medicine and Pediatrics, Cincinnati Children’s Hospital Medical Center, and Director of the NCATS-NHLBI Rare Lung Diseases Clinical Research Consortium. “PAP is a debilitating lung disease with a high clinical need for an effective medicinal treatment to reduce or eliminate the need for whole lung lavage. Inhaled GM-CSF restores the ability of lung cells to clear surfactant. Based on an increasing body of literature and clinical experience of explorative use of inhaled GM-CSF, I and my colleagues treating PAP patients worldwide are very optimistic about the potential of Molgradex as a truly transformative treatment option in PAP.”

The primary endpoint in the IMPALA study will remain the absolute change from baseline in arterial-alveolar oxygen gradient, a measure of patient’s oxygenation status, following 24 weeks of treatment. In addition, the FDA will focus its review on three key secondary endpoints that will be assessed to show improvement in clinical symptoms and function, including six-minute walk distance, St. George’s respiratory questionnaire, and the time to need of whole lung lavage. Patients are randomized to receive treatment for up to 24 weeks in one of three treatment arms: 1) Molgradex 300 µg administered once daily, 2) Molgradex 300 µg and matching placebo administered daily in 7-day intermittent cycles of each, or 3) inhaled placebo administered once daily.

Mast Therapeutics, Inc. is a biopharmaceutical company, which engages in developing novel therapies for serious or life-threatening diseases with significant unmet needs. It leveraging Molecular Adhesion and Sealant Technology, platform, derived from over two decades of clinical, nonclinical, and manufacturing experience with purified and non-purified poloxamers to develop vepoloxamer, which also known as MST-188.