Rare Daily Staff

The U.S. Food and Drug Administration has granted Breakthrough Therapy designation for Molgradex, Savara Pharmaceutical’s inhaled formulation of recombinant human granulocyte-macrophage colony-stimulating factor for the treatment of autoimmune pulmonary alveolar proteinosis.

Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare autoimmune lung disorder and the most common form of pulmonary alveolar proteinosis primarily affecting adults between the ages of 20 to 50 years. Symptoms include progressive difficulty breathing and shortness of breath, chronic cough, fatigue, weight loss, chest pain, and in rare cases coughing up of blood, and rounding and swelling the tips of the fingers.

aPAP is caused by an immune system malfunction, due to IgG antibodies that block the granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) effect. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a protein that regulates clearance of surfactant (a mix of protein and fat) by alveolar macrophages. The surfactant piles up in the air sacs of the lungs and eventually leads to an inability to breathe. The standard treatment is a procedure called lung lavage. A drug called GM-CSF might effectively treat aPAP.

Breakthrough Therapy designation is designed to expedite the development and review of drugs that are intended to treat a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint.

The Molgradex Breakthrough Therapy designation is based on data from IMPALA, a pivotal phase 3 clinical study evaluating Molgradex for the treatment of aPAP. Data from the study, originally presented in June 2019 showed the treatment failed to meet its primary endpoint of significant improvement in oxygen levels due to an unexpectedly high placebo effect. However, the company was able to show improvements in secondary endpoints that Savara said supported Molgradex, including a walking test, CT scans, and hemoglobin levels. The new data was recently presented in an oral session at the 2019 European Respiratory Society (ERS) International Congress in Madrid, Spain.

“We believe this designation reflects the significance of Molgradex as an investigational product that, based on the IMPALA study, has been demonstrated to improve patient outcomes,” said Rob Neville, CEO of Savara. “Breakthrough designation is designed to provide increased collaboration and more frequent dialogue with the FDA and is an important milestone as we work to determine the best path forward for this product.”

Photo: Rob Neville, CEO of Savara

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