Savara reports positive phase 3 results for molgramostim in rare lung disease

Savara has reported promising late-stage results for its molgramostim nebuliser solution (molgramostim) targeting a rare lung condition. The phase 3 IMPALA-2 clinical trial assessed the effectiveness and safety of administering 300mcg of molgramostim daily through inhalation in adult patients with autoimmune pulmonary alveolar proteinosis (aPAP), compared to a placebo.

Chronic respiratory diseases were the third most common cause of global deaths in 2019, arising from various factors such as infections, smoking, exposure to radon, asbestos, or other pollutants. Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare condition affecting approximately one in 150,000 people in the United States. It is characterized by the dysfunction of myeloid cells, abnormal accumulation of pulmonary surfactant, and an innate immune deficiency.

The IMPALA-2 trial successfully met its primary endpoint. The therapy demonstrated an improvement in lung function, particularly in the hemoglobin-adjusted percent predicted DLCO, a measure of the lung's capacity to transfer carbon monoxide. This improvement achieved statistical significance compared to the placebo at 24 weeks and was maintained at 48 weeks.

Bruce Trapnell, the lead investigator of the trial, stated, “With convincing data from two large clinical trials, the evidence now clearly demonstrates molgramostim has the potential to be a safe and efficacious treatment option for [aPAP] patients.” Matt Pauls, Savara's chair and CEO, added, “The strong efficacy data and favorable benefit-risk profile potentially positions molgramostim to be the first and only approved therapeutic for aPAP in the US and Europe.”

Molgramostim, an inhaled form of recombinant human granulocyte-macrophage colony-stimulating factor, has received multiple designations from regulatory bodies. These include Orphan Drug, Fast Track, and Breakthrough Therapy designations from the US Food and Drug Administration (FDA), Orphan Drug Designation from the European Medicines Agency (EMA), and Innovative Passport and Promising Innovative Medicine designations from the UK's Medicines and Healthcare Products Regulatory Agency for the treatment of aPAP.

In related developments, the FDA has recently approved Verona Pharma’s Ohtuvayre (ensifentrine) as a maintenance treatment for adults with chronic obstructive pulmonary disease (COPD), a prevalent lung condition affecting over 390 million people worldwide. Additionally, in May, the EMA’s human medicines committee recommended Sanofi and Regeneron’s Dupixent (dupilumab) as an add-on maintenance treatment for COPD. This followed positive results from the NOTUS trial, which were presented at the 2024 American Thoracic Society International Conference.