Inhaled Drug Appears to Reduce Need for Whole-Lung Lavage for People with aPAP

Published September 2020 | The New England Journal of Medicine

Most people living with autoimmune pulmonary alveolar proteinosis (aPAP) have to report to a hospital about once a year to receive a whole-lung lavage procedure to flush out waste products that their lungs cannot clear away on their own.

That routine might become less necessary based on findings from a 34-center clinical trial led by Bruce Trapnell, MD. The phase 2/3 IMPALA trial demonstrated the potential value of a daily inhaled dose of the drug molgramostim, a recombinant form of the protein GM-CSF (granulating macrophage colony stimulating factor).

The clinical trial, which involved 138 people, represented a major step for what might be the first drug that can help these patients. Autoimmune PAP strikes an estimated seven to 26 people per 1 million population, or roughly 2,000 to 8,000 people in the United States.

“No drugs have been approved for treating PAP in any country, so this one could radically improve the lives of people with aPAP,” Trapnell says.

The phase 2/3 clinical trial results marked a key milestone in a long discovery path. Trapnell and colleagues found out nearly 20 years ago that aPAP was linked to disruption of cell regulation by GM-CSF. In research involving mouse models and patient tissue samples, the scientists learned that the immune systems of people with aPAP neutralize GM-CSF. The new drug restores GM-CSF signaling, which allows lung biology to return to a more normalized state.

Molgramostim, made by Savara Pharmaceuticals, has received Breakthrough Therapy Designation from the U.S. Food & Drug Administration. The first patient in the IMPALA-2 Phase 3 clinical trial received the drug in June 2021.