MediciNova announces results of MN 166 studies under BARDA contract

The company states: “MediciNova announced the results of the nonclinical studies conducted under its contract with the Biomedical Advanced Research and Development Authority, or BARDA, part of the Administration for Strategic Preparedness and Response in the U.S. Department of Health and Human Services, to repurpose MN-166, or ibudilast, as a potential medical countermeasure against chlorine gas-induced lung damage such as acute respiratory distress syndrome and acute lung injury. Two different nonclinical models were used to investigate the potential clinical utility of MN-166 for the treatment of chlorine-induced lung damage. The primary objective of the first nonclinical efficacy study was to determine the safety and pharmacological activity of MN-166 (ibudilast) following ALI induced by chlorine gas inhalation. In this study, single-dose and multi-dose treatments were evaluated. The primary endpoint was the pulmonary function measure PaO2/FiO2, which is the ratio of arterial oxygen partial pressure to fractional inspired oxygen. After a Cl2 gas challenge to induce moderate ALI, the test subjects were divided into four different treatment groups – two different doses of MN-166 , a positive control, and a negative control – which were infused intravenously over 30 minutes. In the pilot design single-dose treatment regimen, the test subjects were treated only once after the Cl2 gas challenge was completed. MN-166 high dose and the positive control were more efficacious than MN-166 low dose and the negative control until 12 hours after Cl2 exposure but this did not yield statistically significant results for overall pulmonary function. MN-166 was well tolerated and no safety concerns were observed in the single-dose study. A pharmacokinetic study was conducted to determine the optimal dosing frequency of MN-166 in the multi-dose study. In the multi-dose study, based on the PK profile in test subjects, each treatment was given every 12 hours with a total of 4 doses after the Cl2 gas challenge. Treatment with MN-166 high dose resulted in greater improvement (p=0.0001) in the mean PaO2/FiO2 ratio than MN-166 (ibudilast) low dose, rolipram, and negative control. The mean PaO2/FiO2 ratio decreased (worsened) by 57% from 518.7 mmHg at baseline (the end of the chlorine gas exposure) to 224.8 mmHg at hour 48 in the negative control group. The mean PaO2/FiO2 ratio decreased (worsened) by 36% from 516.0 mmHg at baseline to 327.8 mmHg at hour 48 in the MN-166 (ibudilast) high dose group. At hour 48, the last time point measured in the study, the mean PaO2/FiO2 ratio was 46% higher (better) in the MN-166 (ibudilast) high dose group than in the negative control group (327.8 vs. 224.8 mmHg). Since ARDS is defined as a PaO2/FiO2 ratio less than 300 mmHg, the mean PaO2/FiO2 ratio values indicate that the negative control group was still categorized as having mild ARDS at the end of the 48-hour evaluation period but the MN-166 (ibudilast) high dose group had recovered enough to no longer be defined as having ARDS. MN-166 (ibudilast) was well tolerated and no safety concerns were observed in the multi-dose study. A preliminary proof-of-concept study was conducted to determine the feasibility of the second nonclinical model as a tool to evaluate MN-166 (ibudilast) as a MCM for chlorine gas exposure. After multiple attempts by MediciNova’s subcontractor to establish the feasibility of the second Cl2-gas induced lung injury model, it was not deemed to be a feasible model to evaluate a drug candidate and there are no evaluable efficacy results from the second nonclinical model POC study.”