Molgramostim in aPAP
Molgramostim is an investigational inhaled formulation of recombinant human GM-CSF. It is being evaluated for the treatment of autoimmune pulmonary alveolar proteinosis, or aPAP, a rare lung disease characterized by the build-up of lung surfactant in the alveoli, or air sacs, of the lungs. The disease process underlying aPAP involves an autoimmune response against GM-CSF, a naturally occurring protein, suppressing the stimulating activity of GM-CSF on lung macrophages which function to clear excess surfactant from the alveoli.
Molgramostim has been granted Orphan Drug Designation for the treatment of aPAP in the U.S. and the European Union. Orphan Drug Designation makes molgramostim eligible for seven years of exclusivity from approval in the U.S., and ten years of exclusivity in the European Union.
Additionally, the U.S. Food & Drug Administration (FDA) granted molgramostim Breakthrough Therapy Designation for the treatment of aPAP. This process is designed to expedite the development and review of drugs that are intended to treat a serious condition and preliminary evidence indicates the drug may demonstrate a substantial improvement over available therapies.
aPAP – autoimmune pulmonary alveolar proteinosis (GM-CSF)
Autoimmune Pulmonary Alveolar Proteinosis (aPAP) is a rare lung disease, which affects approximately 7 people per million. It is characterized by the build-up of grainy material in the air sacs (alveoli) in the lungs. The grainy material consists of proteins and lipids from lung surfactant – an important substance that coats the inside of the air sacs to prevent the lungs from collapsing. The air sacs need to be inflated for the lungs to absorb the oxygen that the patient breathes and transfer it to the blood circulation. The body continuously produces new active surfactant. In healthy lungs the old, inactivated surfactant is digested by immune cells called alveolar macrophages. They are the dustmen or garbage collectors of the body and they have a very important task of keeping the alveoli clean. In aPAP lungs, however, the macrophages fail to clean the air sacs. Consequently, the old surfactant material builds up gradually in the lungs and eventually fills the alveoli causing the patient to feel breathless. Scientific research shows that the macrophages need to be stimulated by the GM-CSF protein in order to function. In a diseased lung, however, the GM-CSF protein is either inactivated or defective, rendering the macrophages or dustmen unable to perform their cleaning tasks. The patient is commonly a man in early middle age who experiences increasing breathing difficulty, first with exertion, later at rest while developing a cough. There may be episodes of fever, chest pain, or coughing blood, especially if secondary lung infection develops. The best available treatment today is periodic whole lung lavage (WLL), i.e. washing out the lungs under general anesthesia. This requires admission to intensive care, which is an invasive and inconvenient procedure that can only be conducted effectively and safely by highly experienced physicians at a few specialist sites.