Eyevinal (ibudilast) / Kyorin, University of Colorado, MediciNova - LARVOL DELTA

Characterization of Ibudilast Pharmacokinetics in the Rat After Intravenously Administration (FOCIS 2025) - "Ibudilast seems to be quickly absorbed in blood after IV injection with a relatively short half-life. The PK data from this study will be used to develop an optimal dose of ibudilast for efficacy studies."

PK/PD data • Preclinical • Immunology • Inflammation

PDE4B Inhibition and Psilocybin as Promising Approaches for Treating Methamphetamine Use Disorder: Preclinical Evidence from Rat Models (CPDD 2025) - "Using preclinical models, we evaluated the effects of 11H, a selective PDE4B inhibitor, and the prototypical PDE4 inhibitors rolipram and ibudilast on remifentanil and MA self-administration and reinstatement behaviors in male and female Sprague-Dawley rats. These findings suggest that PDE4 plays an essential role in mediating drug-seeking behavior and that PDE4 inhibitors, particularly selective PDE4B inhibitors like 11h, may be a promising approach for treating stimulant and opioid use disorders."

Preclinical • Addiction (Opioid and Alcohol) • CNS Disorders • Gastrointestinal Disorder • Psychiatry • Substance Abuse

Inhibition of Activated Coagulation Factor XII by the Phosphodiesterase-4 Inhibitor Roflumilast: In Vitro and In Silico Studies. (PubMed, Front Biosci (Landmark Ed)) - "Overall, roflumilast could be used as a lead compound for developing a novel multifunctional therapeutic drug used for the prevention of HAE or thrombotic disorders."

Journal • Preclinical • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Hereditary Angioedema • Inflammation • Thrombosis

Potential therapeutic effects of ibudilast and retinoic acid against cuprizone-induced behavioral and biochemical changes in mouse brain. (PubMed, Front Mol Neurosci) - "The mRNA expression pattern of various MS associated genes indicated that the treatments effectively mitigated the detrimental effects of CPZ in mouse brain. The findings of this study indicate that RA supplements could be effectively unitized as adjuvant therapy alongside with IBD for MS treatment."

Journal • Preclinical • CNS Disorders • Multiple Sclerosis • STAT3

MN-166-GBM-1201: Study to Evaluate Ibudilast and TMZ Combo Treatment in Newly Diagnosed and Recurrent Glioblastoma (clinicaltrials.gov) - P1/2 | N=64 | Completed | Sponsor: MediciNova | Active, not recruiting ➔ Completed

Trial completion • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

Ibudilast for Treating Alcohol Use Disorder (clinicaltrials.gov) - P2 | N=50 | Active, not recruiting | Sponsor: University of Pennsylvania | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2028 ➔ Dec 2027 | Trial primary completion date: Dec 2027 ➔ Dec 2026

Enrollment closed • Trial completion date • Trial primary completion date • Addiction (Opioid and Alcohol)

Integration of Bioinformatics and Machine Learning Strategies Identifies Ferroptosis and Immune Infiltration Signatures in Peri-Implantitis. (PubMed, Int J Mol Sci) - "Ibudilast and fedratinib were predicted as potential drugs for PI that target TLR4 and FLT3, respectively. Finally, the occurrence of ferroptosis and the expression of the identified key markers in gingival fibroblasts under inflammatory conditions were validated by RT-qPCR and immunofluorescence analysis. This study identified TLR4 and FLT3 as ferroptosis and immune cell infiltration signatures in PI, unraveling potential novel targets to treat PI."

Biomarker • IO biomarker • Journal • Inflammation • FLT3 • TLR4

Cognitive test performance and disease progression in primary and secondary progressive MS: An analysis of the SPRINT-MS study. (PubMed, Mult Scler) - "Observed stability of cognitive scores in individuals with progressive MS over 96-week follow-up may reflect true cognitive stability. However, the possibility that current cognitive measurement instruments are psychometrically flawed remains, warranting further research."

Journal • CNS Disorders • Cognitive Disorders • Multiple Sclerosis

A Neuroimmune Modulator for Alcohol Use Disorder: A Randomized Clinical Trial. (PubMed, JAMA Netw Open) - P2 | "Ibudilast is a neuroimmune modulator which selectively inhibits phosphodiesterases (PDE) 3, PDE4, PDE10, and PDE11, and macrophage migration inhibitory factor (MIF)...As novel treatments for AUD are developed for novel molecular targets, their effects may depend on mechanisms and moderators of efficacy. ClinicalTrials.gov Identifier: NCT03594435."

Clinical • Journal • Addiction (Opioid and Alcohol) • CNS Disorders • Inflammation • MIF

Ibudilast-Mediated Suppression of Neuronal TLR4 in the Prefrontal Cortex Mitigates Methamphetamine-Induced Neuroinflammation and Addictive Behaviours. (PubMed, Addict Biol) - "Furthermore, local injection of Ibudilast in the prefrontal cortex led to a reduction in METH intake and motivation, as well as decreased expression of TLR4 in the brain region. These findings underscore the critical role of neuronal TLR4 in METH addiction and highlight Ibudilast's therapeutic potential in addressing METH-related neuroinflammation and behavioural dysregulation."

IO biomarker • Journal • CNS Disorders • Inflammation • Psychiatry • IL6 • TLR4

First Patient Enrolled in NIH-Funded Expanded Access Program (EAP) Trial to Evaluate MN-166 in Amyotrophic Lateral Sclerosis (ALS) Patients (GlobeNewswire) - "MediciNova...announced enrollment of the first patient in the NIH-funded Expanded Access Program (EAP) trial to evaluate MN-166 (ibudilast) in patients with Amyotrophic Lateral Sclerosis (ALS). This significant milestone marks the beginning of a critical trial aimed at providing access to MN-166 for ALS patients who are not eligible for the ongoing Phase 2/3 COMBAT-ALS trial. The EAP trial, funded by the National Institutes of Health (NIH) - Neurological Disorders and Stroke (NINDS), will evaluate the safety and efficacy of MN-166 in approximately 200 ALS patients."

Trial status • Amyotrophic Lateral Sclerosis

Metabolic activation and cytotoxicity of ibudilast mediated by CYP3A4. (PubMed, Arch Toxicol) - "Pretreatment of mice hepatocytes with ketoconazole attenuated the susceptibility to the cytotoxicity of IBD (25-400 μM). The reactive epoxide intermediate might correlate the hepatotoxicity induced by IBD. This work revealed the reactive epoxide intermediate might correlate the hepatotoxicity induced by IBD, and would provide new insights into the mechanisms behind the adverse reactions taking place in clinical use of IBD, especially for the reported liver injury."

Journal • Asthma • CNS Disorders • Hepatology • Immunology • Liver Failure • Multiple Sclerosis • Pain • Pulmonary Disease • Respiratory Diseases • CYP3A4

Drug repositioning based on mutual information for the treatment of Alzheimer's disease patients. (PubMed, Med Biol Eng Comput) - "The results also highlight the diagnostic role of the 25 genes since we obtained good classification performances using a neural network model. We also suggest 12 repurposable drugs (like KU-60019, AM-630, CP55940, enflurane, ginkgolide B, linopirdine, apremilast, ibudilast, pentoxifylline, roflumilast, acitretin, and tamibarotene) interacting with 6 genes (ATM, CNR1, GLRB, KCNQ2, PDE4B, and RARA), that we linked to retrograde endocannabinoid signaling, synaptic vesicle cycle, morphine addiction, and homologous recombination."

Journal • Alzheimer's Disease • CNS Disorders • Psychiatry • ATM

RECLAIM: Recovering From COVID-19 Lingering Symptoms Adaptive Integrative Medicine (clinicaltrials.gov) - P2/3 | N=460 | Active, not recruiting | Sponsor: University Health Network, Toronto | Suspended ➔ Active, not recruiting | Trial completion date: Dec 2026 ➔ Mar 2025 | Trial primary completion date: May 2026 ➔ Mar 2025

Enrollment closed • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

Ibudilast Protects Retinal Bipolar Cells From Excitotoxic Retinal Damage and Activates the mTOR Pathway. (PubMed, Glia) - "The mTOR inhibitor rapamycin blocked accumulation of pS6 but did not reduce TUNEL positive dying cells. We have identified several paracrine signaling pathways that are known to contribute to cell survival and neuroprotection and might play essential roles in ibudilast function. These findings highlight ibudilast's potential to protect inner retinal neurons during damage and show promise for future clinical translation."

Journal • CNS Disorders • CD74 • MIF

RECLAIM: Recovering from COVID-19 Lingering Symptoms Adaptive Integrative Medicine (clinicaltrials.gov) - P2/3 | N=460 | Suspended | Sponsor: University Health Network, Toronto | N=1000 ➔ 460 | Recruiting ➔ Suspended

Enrollment change • Trial suspension • Infectious Disease • Novel Coronavirus Disease

Neurotherapeutic impact of vanillic acid and ibudilast on the cuprizone model of multiple sclerosis. (PubMed, Front Mol Neurosci) - "IBD improved behavioral abnormalities across all tests, but combined therapy showed no significant difference from single therapies. Further investigations are necessary to understand VA's mechanisms and potential as an MS treatment."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Multiple Sclerosis

The Role of Glial Cells in Autism Spectrum Disorder: Molecular Mechanisms and Therapeutic Approaches. (PubMed, CNS Neurol Disord Drug Targets) - "Minocycline and ibudilast have shown potential for modulating microglial activity and reducing neuroinflammation. This abstract underscores the importance of glial cells in ASD. It highlights the need for further research to elucidate the complex interactions between glial dysfunction and ASD pathogenesis, aiming to develop targeted therapies that can ameliorate the clinical manifestations of ASD."

Journal • Autism Spectrum Disorder • Genetic Disorders • Inflammation

SEANOBI-ALS: Scalable Expanded Access with Analysis of Neurofilament and Other Biomarkers for Ibudilast in ALS (clinicaltrials.gov) - P=N/A | N=0 | Available | Sponsor: Mayo Clinic

Biomarker • New trial

MediciNova Presents Study Update and Interim Analysis of Phase 2/3 Clinical Trial of MN-166 (ibudilast) in ALS (COMBAT-ALS Clinical Trial) at the 35th International Symposium on ALS/MND (GlobeNewswire) - P2b/3 | N=230 | COMBAT-ALS (NCT04057898) | Sponsor: MediciNova | "The highlights of the presentation...include:...Positive correlations were observed between the 6-month and 12-month data for CAFS score (0.71), modified CAFS score (0.70), and ALSFRS-R (0.69)...Positive correlations were also observed for Bulbar score (0.74), Fine motor score (0.71), and Gross motor score (0.67), but not for Respiratory score...Interim analysis results were reviewed and validated by an external independent Data Safety Monitoring Board (DSMB), which recommended that the trial continue as per the protocol...'if we continue to actively enroll in the COMBAT-ALS study, we expect to complete patient assignments by June 2025 with trial results expected in 2026...Next year, the NIH-funded, large-scale Expanded Access Program trial is set to begin, and we look forward to the opportunity to provide access to MN-166 to more ALS patients.'"

Enrollment status • New trial • P2/3 data • Amyotrophic Lateral Sclerosis • CNS Disorders

RECLAIM: Recovering From COVID-19 Lingering Symptoms Adaptive Integrative Medicine (clinicaltrials.gov) - P2/3 | N=1000 | Recruiting | Sponsor: University Health Network, Toronto | Trial completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: May 2025 ➔ May 2026

Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

COMBAT-ALS Phase 2b/3 trial of MN-166 (Ibudilast) in ALS: trial update and interim analysis results (ALS-MND 2024) - P2/3 | "The trial continues after the interim analysis now with 154 of 230 participants randomized. With projected completion of enrollment 1st quarter 2025. Trial update and interim analysis results from ongoing Phase 2b/3 trial evaluating MN-166 in patients with ALS will be reported."

P2/3 data • P2b data • MIF

WideTrial Supports NIH-Funded Expanded Access Program for Investigational ALS Drug (PRNewswire) - "WideTrial...announced its participation in an NIH-funded collaboration to provide pre-approval access to an investigational ALS drug. The program will offer access to ibudilast, an experimental drug being studied for its potential to slow the progression of ALS, to patients who are ineligible for clinical trials. The program is funded by a $22 million grant from the National Institute of Neurological Disorders and Stroke (NINDS) and will be led by Dr. Bjorn Oskarsson at Mayo Clinic's ALS Center of Excellence in Jacksonville, Florida. It aims to enroll 200 ALS patients across all three Mayo Clinic centers and other participating institutions."

Financing • Amyotrophic Lateral Sclerosis

Ibudilast and anti-PD-L1 Combination Treatment Significantly Improves Survival in a Sex-dependent Manner in a Murine Model of Glioblastoma (SNO 2024) - "Ibudilast with anti-PD-L1 is a promising combination treatment against GBM. Future research is needed to identify the mechanisms underlying this treatment regimen and its sex-dependent effect. These results may inform the development of a combination new clinical trial, as ibudilast is currently being evaluated in the newly-diagnosed and recurrent GBM setting with temozolomide."

Preclinical • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • CD74 • MIF

Morphine self-administration is inhibited by the antioxidant N-acetylcysteine and the anti-inflammatory ibudilast; an effect enhanced by their co-administration. (PubMed, PLoS One) - "Separate or joint administration of an antioxidant and anti-inflammatory agent reduced voluntary opioid intake, which could have translational value for the treatment of opioid use disorders, particularly in settings where the continued maintenance of oral opioids is a therapeutic option."

Journal • Addiction (Opioid and Alcohol) • CNS Disorders • Inflammation • Psychiatry • Substance Abuse