Savara Inc. (Nasdaq: SVRA) has announced the initiation of a rolling submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for MOLBREEVI, a promising treatment for autoimmune pulmonary alveolar proteinosis (aPAP). This rare and progressive lung disease is characterized by an abnormal buildup of surfactant in the lungs, leading to debilitating respiratory symptoms. The submission marks a significant step toward addressing the unmet medical need for aPAP patients, as there are currently no approved medicines for this condition in the U.S. and Europe.
Regulatory Pathway and Designations
MOLBREEVI has been granted several key designations by the FDA, including Fast Track and Breakthrough Therapy designations in 2019, as well as Orphan Drug status from both the FDA and the European Medicines Agency (EMA). These designations are reserved for drugs that address serious medical conditions and demonstrate potential advantages over existing therapies. The rolling submission process allows Savara to submit sections of the BLA as they are completed, potentially accelerating the overall review timeline. The company plans to request a priority review of the application upon completion of the submission, which is expected by the end of the first quarter of 2025.
Clinical Evidence from IMPALA-2 Trial
The BLA submission is supported by positive results from the pivotal Phase 3 IMPALA-2 trial. This trial evaluated the efficacy and safety of MOLBREEVI in patients with aPAP. According to Matt Pauls, Chair and CEO of Savara, the company believes that MOLBREEVI demonstrates a favorable benefit-risk profile and could fundamentally change the way aPAP is treated. The IMPALA-2 trial met its primary endpoint, demonstrating a statistically significant change from baseline in DLCO (diffusing capacity for carbon monoxide) at week 24. This effect was sustained at week 48, a secondary endpoint, indicating durability of the treatment's benefits.
Autoimmune Pulmonary Alveolar Proteinosis (aPAP)
Autoimmune PAP is a rare lung disease affecting approximately 7 in 1 million people in the United States. It results from the abnormal accumulation of surfactant in the alveoli of the lungs, impairing gas exchange and causing symptoms such as shortness of breath, cough, and fatigue. In a healthy lung, alveolar macrophages clear excess surfactant, a process stimulated by granulocyte-macrophage colony-stimulating factor (GM-CSF). However, in aPAP, antibodies neutralize GM-CSF, preventing macrophages from effectively clearing surfactant. Current management of aPAP typically involves whole lung lavage, an invasive procedure requiring the flushing of the lungs with large volumes of saline.
MOLBREEVI: A Targeted Therapy
MOLBREEVI (molgramostim) is a recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) administered via a nebulizer. It is designed to stimulate alveolar macrophages, restoring their ability to clear the buildup of proteins and fats in the alveoli. If approved, MOLBREEVI would represent the first targeted therapy for aPAP, offering a significant advancement over the current standard of care.
Safety Profile
Data from the IMPALA-2 trial indicated that the frequency of adverse events was generally similar between the MOLBREEVI and placebo groups. Two patients (2.5%) discontinued MOLBREEVI treatment due to adverse events, neither of which were considered related to the trial drug. The most commonly reported adverse events in the MOLBREEVI group were COVID-19, cough, and pyrexia, with COVID-19 occurring more frequently in the MOLBREEVI group than in the placebo group.
Addressing Unmet Needs
Savara's proactive regulatory strategy underscores the significant unmet need for effective treatments for aPAP. The initiation of the BLA submission for MOLBREEVI represents a crucial step toward providing an innovative solution for patients and their families, reinforcing Savara's commitment to addressing rare diseases.
