MediciNova Inc. Announces FDA Approval of the Second Phase 2 Protocol for MN-001 in NASH Which Targets NASH Patients With Hypertriglyceridemia
Jul 27 15
MediciNova Inc. announced that FDA (U.S. Food and Drug Administration) has approved a second protocol for a clinical trial evaluating MN-001 (tipelukast) for a NASH indication. This study targets NASH patients with hypertriglyceridemia to evaluate the ability of MN-001 to improve cardiovascular risk by assessing cholesterol-efflux capacity and serum triglyceride levels as well as reduction of percentage fat in the liver, as assessed by MRI. The Phase 2 trial is a single-center, proof-of-principle, open-label study designed to evaluate the efficacy, safety, and tolerability of MN-001 in subjects with nonalcoholic steatohepatitis (NASH) and hypertriglyceridemia. Eligible subjects will consist of males and females ranging in age from 21 to 65 years old, inclusive. To be eligible, subjects must have a histologically confirmed diagnosis of NASH within 6 months prior to the baseline visit and an elevated serum triglyceride (> 150 mg/dL) during the Screening Phase. Approximately twenty (20) qualifying subjects will be given MN-001 250 mg orally administered once a day for the first 4 weeks and will be given MN-001 250 mg twice a day for an additional 8 weeks. Overall, the study timeline consists of a Screening Phase (up to 4 months) followed by a Treatment Phase (12 weeks), and a Follow-up visit (within 1 week after the last dose). The primary efficacy endpoints of the study are to evaluate the effect of MN-001 on 1) Triglyceride levels in NASH subjects with hypertriglyceridemia, and 2) Cholesterol Efflux Capacity in NASH subjects with hypertriglyceridemia. Secondary endpoints include safety and tolerability of MN-001, PK profile of MN-001/MN-002 (by-product of MN-001), effects of MN-001 on HDL-C, LDL-C, and total cholesterol level, and effects of MN-001/002 on liver enzymes and percentage fat in liver assessed using MRI at Week 12. Earlier this year, the FDA granted Fast-Track designation to MN-001 for the treatment of NASH with fibrosis. Fast Track is a process designed to facilitate the development and expedite the review of drugs that are intended to treat serious or life-threatening diseases and demonstrate the potential to address unmet medical needs for such diseases. An important feature of the FDA's Fast Track program is that it emphasizes frequent communication between the FDA and the sponsor throughout the entire drug development and review process to improve the efficiency of product development. Accordingly, Fast Track status can potentially lead to a shortened timeline to ultimate drug approval. Nonalcoholic steatohepatitis (NASH) is a condition in which there is fat in the liver along with inflammation and damage to liver cells. NASH is a common liver disease that resembles alcoholic liver disease but occurs in people who drink little or no alcohol. According to the U.S. National Digestive Diseases Information Clearinghouse (NDDIC), NASH prevalence in the U.S. is 2-5%, and an additional 10-20% of Americans have "fatty liver." The underlying cause of NASH is unclear, but it most often occurs in people who are middle-aged and overweight or obese. Many patients with NASH have elevated serum lipids, diabetes or pre-diabetes. Progression of NASH can lead to liver cirrhosis. Liver transplantation is the only treatment for advanced cirrhosis with liver failure. At this time, there is no treatment for NASH. MN-001 (tipelukast) is a novel, orally bioavailable small molecule compound thought to exert its effects through several mechanisms to produce its anti-inflammatory and anti-fibrotic activity in preclinical models, including leukotriene (LT) receptor antagonism, inhibition of phosphodiesterases (PDE) (mainly 3 and 4), and inhibition of 5-lipoxygenase (5-LO). The 5-LO/LT pathway has been postulated as a pathogenic factor in fibrosis development and MN-001's inhibitory effect on 5-LO and the 5-LO/LT pathway is considered to be a novel approach to treat fibrosis. MN-001 has been shown to down-regulate expression of genes that promote fibrosis including LOXL2, Collagen Type 1 and TIMP-1. MN-001 has also been shown to down-regulate expression of genes that promote inflammation including CCR2 and MCP-1. In addition, histopathological data shows that MN-001 reduces fibrosis in multiple animal models. Previously, MediciNova evaluated MN-001 for its potential clinical efficacy in asthma and had positive Phase 2 results. MN-001 has been exposed to more than 600 subjects and is considered generally safe and well-tolerated. Importantly, in these studies, reduction of serum triglyceride was observed for those treated with MN-001 in healthy volunteers and target populations.
MediciNova Inc., Q2 2015 Earnings Call, Jul 31, 2015
Jul 24 15
MediciNova Inc., Q2 2015 Earnings Call, Jul 31, 2015
MediciNova Announces Update on Development Plans for MN-001 in IPF
Jul 21 15
MediciNova Inc. announced that it is currently in late-stage discussions with investigators at Penn State University to conduct a Phase 2 study of MN-001 (tipelukast) for the treatment of moderate to severe IPF (idiopathic pulmonary fibrosis). The Phase 2 trial is a randomized, placebo-controlled, double blind 6-month study followed by an open-label extension phase to evaluate the efficacy, safety, and tolerability of MN-001 in subjects with moderate to severe IPF. Approximately fifteen qualifying subjects will be randomly assigned in a 2:1 ratio to MN-001 750 mg or matching placebo orally administered twice a day for 26 weeks (double-blind treatment phase). After completion of the double-blind treatment phase, subjects will participate in the open-label extension (OLE) phase for an additional 6 months. Subjects who were in the placebo group will be administered MN-001 750 mg twice a day for remainder of the OLE Phase. Subjects randomized to the MN-001 group will continue on MN-001 for additional 6 months. A follow-up visit will occur within 4 weeks after last dose. The primary efficacy endpoints of the study are to evaluate the effect of MN-001 on 1) change from baseline of forced vital capacity (FVC) and FVC% predicted up to 26 weeks, and 2) the semiannual rate of decline of disease activity based on forced vital capacity (FVC). Secondary endpoints include safety and tolerability, semiannual rate of decline on disease activity based on the 6-minute walk test (6MWT), change from baseline on disease activity based on Modified Medical Research Council Dyspnea Score (MMRC), change from baseline on quality of life (QOL) measured by A Tool to Assess Quality of Life in Idiopathic Pulmonary Fibrosis (ATAQ-IPF), frequency of worsening IPF, and time to first worsening of IPF. FDA has already approved the protocol for this clinical trial of MN-001 (tipelukast) for the treatment of moderate to severe IPF (idiopathic pulmonary fibrosis). Importantly, due to safety data from previous clinical studies of MN-001, FDA agreed that MediciNova may proceed with a Phase 2 study as the first clinical trial of MN-001 in IPF.