Savara Begins Rolling BLA for Molbreevi for Rare Lung Disease

Pharmaceutical company Savara has initiated a rolling biologics license application (BLA) with the FDA for its drug Molbreevi (molgramostim) as potential treatment of the rare lung disease autoimmune pulmonary alveolar proteinosis (aPAP), according to a recent press release.

Savara expects to complete the submission by the end of the first quarter of 2025. The company will request a priority review of the BLA when submission is completed. Molbreevi was granted fast track and breakthrough therapy designations in 2019, orphan drug designation for the treatment of aPAP.

Autoimmune pulmonary alveolar proteinosis is a rare lung disease that affects approximately 7 in 1 million people in the United States, the American Lung Association says. It is caused by a build up of proteins and fats in the alveoli, or air sacs, of the lungs, which prevents air from getting through the alveoli. Patients with aPAP experience shortness of breath, cough and secondary lung infections. In severe cases, a lung transplant may be required. The only option to clear excess fluid from the lungs is by performing a lung lavage, in which the lung is flushed out by upwards of 50L of saline and then drained by gravity.

Molbreevi is a recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) that is administered using a nebulizer. Molbreevi is believed to activate macrophages in the lung alveoli, thus potentially restoring their ability to clear the build up of proteins and fats.

The application for Molbreevi is based on data from the ongoing phase 3 IMPALA-2 global trial in which 164 patients received Molbreevi or placebo. Effectiveness was measured using the diffusing capacity for carbon monoxide (DLCO) test, which measures how well the lungs transfer gas from the air into the bloodstream.

Topline data released in June 2024 show the trial met its primary endpoint. At week 24, there was a statistically significant change from baseline in DLCO. Additionally, this was sustained at week 48, a secondary endpoint, which demonstrated durability of effect.

The frequency of adverse events was generally similar between treatment groups. Two patients (2.5%) discontinued Molbreevi treatment due to adverse events, both of which were considered unrelated to trial drug. The most commonly reported adverse events in the Molbreevi group were COVID-19, cough, and pyrexia, with COVID-19 occurring more frequently with Molbreevi than with placebo.

In September 2024, the company began an expanded access program to provide patients with early access to Molbreevi. The program enables physicians to require the drug for eligible patients.