MediciNova Announces Results of Studies under BARDA Contract to Develop MN 166 (ibudilast) as a Medical Countermeasure Against Chlorine Gas-induced Lung Injury
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 (Cl2) 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 (mean PaO2/FiO2<200), the test subjects were divided into four different treatment groups - two different doses of MN-166 (ibudilast) (low dose and high dose), a positive control (rolipram), and a negative control (test article vehicle) - which were infused intravenously (IV) 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 (ibudilast) high dose and the positive control were more efficacious than MN-166 (ibudilast) 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 (ibudilast) was well tolerated and no safety concerns were observed in the single-dose study. A pharmacokinetic (PK) study was conducted to determine the optimal dosing frequency of MN-166 (ibudilast) 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 (ibudilast) 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 (POC) 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.
This project has been funded in whole or in part with federal funds from the Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority, under contract number 75A50121C00022.
About MN-166 (ibudilast)
MN-166 (ibudilast) is a small molecule compound that inhibits phosphodiesterase type-4 (PDE4) and inflammatory cytokines, including macrophage migration inhibitory factor (MIF). It is in late-stage clinical development for the treatment of neurodegenerative diseases such as ALS (amyotrophic lateral sclerosis), progressive MS (multiple sclerosis), and DCM (degenerative cervical myelopathy); and is also in development for glioblastoma, Long COVID, CIPN (chemotherapy-induced peripheral neuropathy), and substance use disorder. In addition, MN-166 (ibudilast) was evaluated in patients that are at risk for developing acute respiratory distress syndrome (ARDS).
Statements in this press release that are not historical in nature constitute forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, without limitation, statements regarding the future development and efficacy of MN-166, MN-001, MN-221, and MN-029. These forward-looking statements may be preceded by, followed by, or otherwise include the words "believes," "expects," "anticipates," "intends," "estimates," "projects," "can," "could," "may," "will," "would," “considering,” “planning” or similar expressions. These forward-looking statements involve a number of risks and uncertainties that may cause actual results or events to differ materially from those expressed or implied by such forward-looking statements. Factors that may cause actual results or events to differ materially from those expressed or implied by these forward-looking statements include, but are not limited to, risks of obtaining future partner or grant funding for development of MN-166, MN-001, MN-221, and MN-029 and risks of raising sufficient capital when needed to fund
Source: MediciNova, Inc.
View printer-friendly version