Pulmonary Fibrosis (IPF)
Idiopathic Pulmonary Fibrosis (IPF) is a progressive and generally fatal interstitial lung disease with unknown etiology characterized by a unique pattern of scarring, inflammation, proliferation of fibroblasts, and deposition of connective-tissue matrix proteins in the lungs. This scarring (fibrosis) and inflammation results in dyspnea and poor gas exchange. It is irreversible, has an unpredictable and variable clinical course and is associated with an extremely poor prognosis.
According to the Coalition for Pulmonary Fibrosis, IPF is a rare disease and affects approximately 128,000 people in the U.S., with about 48,000 new cases diagnosed annually. The prognosis for IPF is poor and about two-thirds of IPF patients die within five years of diagnosis.
FDA has granted Orphan-drug designation to MN-001 for the treatment of IPF, which will provide MediciNova with seven years of marketing exclusivity if MN-001 is approved for IPF.
Bleomycin-induced pulmonary fibrosis in the mouse is widely used as animal model of pulmonary fibrosis. MN-001, which was administered orally once daily (30, 100 and 300 mg/kg) for 2 weeks, was evaluated in a mouse model of bleomycin-induced pulmonary fibrosis (PF) as measured by CT evaluation of lung density, degree of pulmonary fibrosis using the Ashcroft score based on histopathological staining, and hydroxyproline content, which is an indicator of fibrosis or storage of collagen in tissue.
MN-001 significantly decreased (p<0.05) the Ashcroft score compared to Vehicle group after 2 weeks of treatment and MN-001 reduced lung density when compared to the Vehicle-treated group. Moreover, lung hydroxyproline content was significantly reduced compared to the Vehicle group (p<0.01). These results show that treatment with MN-001 has significant anti-fibrogenic effects in bleomycin-induced pulmonary fibrosis in mice.
Recent preclinical results provide compelling evidence that MN-001 warrants further evaluation for the treatment of IPF in humans. MediciNova previously opened an Investigational New Drug (IND) application with the Division of Pulmonary, Allergy, and Rheumatology Products (DPARP) for MN-001. Due to safety data from previous clinical studies of MN-001, FDA has approved the protocol for a Phase 2 study as the first clinical trial of MN-001 in IPF.