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

Phosphodiesterase Inhibition Increases Striatal GDNF and Protects Against Preclinical Parkinsonism. (PubMed, J Neurochem) - "In a chronic MPTP mouse model of PD, Ibudilast treatment conferred significant neuroprotection, as evidenced by preservation of tyrosine hydroxylase-positive (TH+) neurons in the substantia nigra, attenuation of TH+ fiber loss in the striatum, and mitigation of striatal dopamine depletion. Given its established clinical use and favorable safety profile, these findings support further investigation of Ibudilast as a potential disease-modifying therapy in PD."

Journal • Preclinical • CNS Disorders • Movement Disorders • Parkinson's Disease

MediciNova Announces Update and Basic Characteristic Randomized Patients’ of Phase 2/3 Clinical Trial of MN-166 (Ibudilast) in ALS (COMBAT-ALS Clinical Trial) Presented at the 36th International Symposium on ALS/MND (GlobeNewswire) - "Baseline Characteristics: Total randomized patients: 234 (Female: 86 [36.8%], Male: 148 [63.2%]); Mean age at screening: 60.6 years; Racial distribution: Caucasian (90.2%), Asian (5.1%), African American (1.3%), Native Hawaiian or Other Pacific Islander (0.4%), American Indian or Alaskan Native (0.4%), Other (2.6%); ALS onset type: Upper limb (46.2%), Lower limb (32.5%), Bulbar (20.9%), Unknown (0.4%); Mean ALSFRS-R score at screening: 40.6; Mean disease duration from first symptom: 12.5 months...'We anticipate top-line data by the end of 2026...'"

P2/3 data • Trial status • Amyotrophic Lateral Sclerosis

Effect of Ibudilast vs Placebo on GFAP and Contactin levels in a phase 2 clinical trial in progressive multiple sclerosis. (PubMed, Neurol Open Access) - P2 | "We found that although ibudilast treatment previously was associated with positive effects on MRI measures of MS disease, it didn't affect GFAP or contactin. The generalizability of these findings regarding the utility of GFAP or contactin as a treatment response biomarker in progressive MS requires further study.Registered on ClinicalTrials.gov: NCT01982942."

Journal • P2 data • CNS Disorders • Multiple Sclerosis • CNTN • GFAP

Associations Between Baseline C-Reactive Protein Levels and Drinking and Craving Outcomes in a Clinical Trial of a Neuroimmune Modulator for Alcohol Use Disorder [WITHDRAWN] (Neuroscience 2025) - "This study is a secondary analysis of a recently completed 12-week randomized controlled trial testing ibudilast (IBUD), a phosphodiesterase inhibitor with anti-inflammatory properties, as a treatment for AUD...Among high-CRP individuals, IBUD was associated with greater reductions in craving over the trial compared to placebo, while craving outcomes were similar across medication conditions among low-CRP individuals. These findings suggest that IBUD, a neuroimmune modulator, may be more effective for individuals with high baseline levels of inflammation, particularly in reducing craving, while the effects on drinking varied across phases of the trial."

Clinical • Addiction (Opioid and Alcohol) • CNS Disorders • CRP

COMBAT-ALS phase 2b/3 trial of MN-166 (ibudilast) in ALS: trial update and baseline characteristics (ALS-MND 2025) - P2, P2/3 | "Participants are allowed to be on riluzole and edaravone and other approved ALS treatments. This update summarizes the current status and baseline characteristics of currently enrolled participants in the COMBAT-ALS trial. The demographic and clinical profile of the enrolled population is consistent with those reported in other Phase 2 and Phase 3 ALS trials, supporting the generalizability of the study findings."

P2/3 data • P2b data • MIF

MediciNova Wins Contract Research and Development Innovation Award at 2025 BioTech Breakthrough Awards (GlobeNewswire) - "MediciNova earned this recognition for its innovative work advancing MN-166 (ibudilast), the company’s lead small molecule drug candidate, currently in development for several neurological diseases, including amyotrophic lateral sclerosis (ALS), one of the fatal neurodegenerative diseases."

Commercial • Amyotrophic Lateral Sclerosis

Repurposing immunomodulatory drugs targeting microglia for amyotrophic lateral sclerosis. (PubMed, Brain Res) - "Compounds such as ibudilast, fingolimod, and modafinil have shown encouraging initial clinical results, whereas others were well-tolerated but underpowered or failed to demonstrate efficacy. New candidates, such as azithromycin, naltrexone, montelukast, doxycycline, tofacitinib, quercetin, belinostat, and several kinase inhibitors, have demonstrated positive preclinical results, supporting their advancement toward clinical evaluation...To realize this potential, future studies must include larger cohorts, assess effects across disease stages and patient subgroups, and examine sex differences. This is essential to address patient heterogeneity and improve personalized treatment in ALS."

Journal • Review • Amyotrophic Lateral Sclerosis • CNS Disorders • Inflammation

Exploring Ferroptosis-Related Genes in Depression: Insights Into Molecular Mechanisms and Potential Therapies. (PubMed, Int J Gen Med) - "We identified five potential small-molecule compounds (VX-702, gossypol, atomoxetine, TWS-119, and ibudilast) that may target these ferroptosis-related pathways...This study provides evidence supporting the involvement of ferroptosis-related mechanisms in depression and proposes a integrative treatment strategy combining targeted molecular interventions with TCM approaches. The findings offer new perspectives for developing therapeutic interventions, particularly for treatment-resistant depression."

Journal • CNS Disorders • Depression • Inflammation • Mood Disorders • Psychiatry

Bioinformatics-based screening and validation of ferroptosis-related genes in sepsis and type 2 diabetes mellitus. (PubMed, Exp Biol Med (Maywood)) - "Echinacea and Ibudilast were predicted to possess the greatest preclinical potential among them. This study provides a deeper insight into the shared pathogenesis of sepsis and T2DM, highlighting the pivotal role of ferroptosis in the development and progression of this comorbidity. Our findings offer preliminary insights into the sepsis-T2DM comorbidity, highlighting ferroptosis as a potential key pathological mechanism and identifying candidate targets for future therapeutic exploration."

Journal • Diabetes • Infectious Disease • Metabolic Disorders • Septic Shock • Type 2 Diabetes Mellitus • CDC25B • CNPY2 • FBXO31 • GNRP • NCOA4

Ibudilast perpetuates stress-induced anxiety-like behavior and fear memory expression in adult Sprague-Dawley rats. (PubMed, J Pharmacol Exp Ther) - "SIGNIFICANCE STATEMENT: Ibudilast, a glial cell inhibitor and promising treatment candidate for various psychiatric disorders, was found to prolong fear expression and anxiety-like behavior in stress-exposed rats. Results suggest added characterization and consideration of its interactions with traumatic stress is needed."

Journal • Preclinical • CNS Disorders • Inflammation • Mental Retardation • Mood Disorders • Psychiatry

A comprehensive systematic review of Ibudilast as a neuroprotective therapy for progressive multiple sclerosis. (PubMed, Mult Scler Relat Disord) - "Ibudilast demonstrates robust neuroprotection in progressive MS, particularly PPMS, with benefits on brain and retinal atrophy and chronic lesion activity."

Journal • Review • CNS Disorders • Inflammation • Multiple Sclerosis • NEFL

Ibudilast Attenuates the Association Between Pain Intensity and Heavy Drinking in Alcohol Use Disorder: A Secondary Analysis of a Randomized Clinical Trial. (PubMed, Alcohol) - "Ibudilast attenuated the positive association between baseline pain intensity and heavy drinking, suggesting that pain intensity may identify an AUD subgroup more likely to benefit from neuroimmune-targeted pharmacotherapy. These findings support incorporating pain phenotyping into AUD treatment research and point toward a precision medicine approach to enhance treatment efficacy."

Clinical • Journal • Addiction (Opioid and Alcohol) • Immunology • Pain

Immune modulatory and vascular protective effects of Ibudilast in post-stroke inflammation. (PubMed, Biomed Pharmacother) - "These microvascular improvements were accompanied by a significant reduction in infarct volume (>50 %) at 24hPR compared to vehicle-treated controls. Together, these findings highlight Ibudilast's therapeutic potential for preserving microvascular integrity and guiding adjunctive interventions to mitigate futile recanalization in acute ischemic stroke."

Journal • Cardiovascular • Inflammation • Ischemic stroke

Impact oft the microenvironment of brain metastases for therapy efficacy (EANO 2025) - "In microglia/macrophages, we identified a CD74⁺ subpopulation reprogrammed by tumour-derived MIF to drive disease through a non-canonical NF-κB pathway, targetable with the brain-penetrant drug ibudilast. Finally, we translated these findings into patient-derived organotypic cultures, enabling preclinical testing of microenvironment-targeted therapies. Our work exposes novel therapeutic vulnerabilities and provides a framework for developing microenvironment-focused clinical strategies in brain metastases."

Clinical • Oncology • Solid Tumor • CD74 • STAT3 • TIMP1

Variations in alcohol craving and negative mood during a clinical trial of ibudilast for alcohol use disorder. (PubMed, Alcohol Clin Exp Res (Hoboken)) - "Consistent with prior research, ibudilast reduced neurobiological and self-report markers of craving, with female participants showing a stronger treatment response by trial endpoint. Despite shared neuroimmune correlates between negative mood and addiction, ibudilast did not alleviate negative mood symptoms beyond placebo effects."

Clinical • Journal • Addiction (Opioid and Alcohol) • CNS Disorders • Depression • Mood Disorders • Psychiatry

MediciNova Announces Completion of Patient Enrollment in COMBAT-ALS Phase 2b/3 Clinical Trial of MN-166 (ibudilast) (GlobeNewswire) - "A total of 234 patients have been randomized across two treatment arms at multiple clinical sites in the United States and Canada....Top-line data are expected by the end of 2026."

Enrollment closed • P2/3 data • Amyotrophic Lateral Sclerosis

Transcanal Endoscopic Tympanoplasty for the Treatment of Localized Eosinophilic Otitis Media in the Tympanic Cavity: A Report of Two Cases. (PubMed, Cureus) - "This report demonstrates the potential applicability of tympanoplasty in selected patients with EOM, despite traditional contraindications. Furthermore, it highlights the effectiveness of combining three antiallergic agents (ibudilast, montelukast, and cetirizine) in controlling postoperative eosinophilic inflammation."

Journal • Infectious Disease • Inflammation • Otorhinolaryngology • Respiratory Diseases • Sinusitis

Angiogenesis and Hypoxia Biomarkers Are Dysregulated in Progressive Multiple Sclerosis. (PubMed, Neurol Neuroimmunol Neuroinflamm) - "Hypoxia-angiogenesis signals are dysregulated in PMS. Increased hypoxia and an insufficient angiogenic adaptive response may play a role in PMS pathophysiology and be a relevant pathway, both in understanding disease mechanisms and as a possible therapeutic target."

Biomarker • Journal • CNS Disorders • Multiple Sclerosis • HBEGF • HGF • HIF1A • HMOX1 • LEP

COMBAT-ALS: Evaluation of MN-166 (Ibudilast) for 12 Months Followed by an Open-label Extension for 6 Months in Patients With ALS (clinicaltrials.gov) - P2/3 | N=234 | Active, not recruiting | Sponsor: MediciNova | Recruiting ➔ Active, not recruiting

Enrollment closed • Amyotrophic Lateral Sclerosis • CNS Disorders

MediciNova…announced that an abstract regarding the Phase 2b/3 COMBAT clinical trial of MN-166 (ibudilast) in…ALS patients has been selected for a poster presentation at 36th International Symposium on ALS/MND (GlobeNewswire)

P2/3 data • Amyotrophic Lateral Sclerosis

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

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

Pilot Study of the Effect of Ibudilast on Neuroinflammation in Methamphetamine Users (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: VA Office of Research and Development | Trial completion date: Dec 2025 ➔ Jun 2026 | Trial primary completion date: Jun 2025 ➔ Dec 2025

Trial completion date • Trial primary completion date • Inflammation

Diffusion tensor imaging in the SPRINT-MS clinical trial: Advancing trial methodology. (PubMed, Mult Scler J Exp Transl Clin) - "SPRINT-MS was a placebo-controlled phase 2 trial of ibudilast in secondary and primary progressive multiple sclerosis...Radial diffusivity was unchanged (declined) in the treatment (placebo) groups, consistent with preservation (deterioration) of tissue integrity. Our results suggest that the diffusion tensor imaging of the cingulum and cerebellar peduncles may be useful target outcome metrics in neuroprotective trials in progressive multiple sclerosis."

Journal • CNS Disorders • Multiple Sclerosis

MediciNova Provides Enrollment Update for Ongoing ALS and Hypertriglyceridemia Clinical Trials (GlobeNewswire) - "MediciNova, Inc...and the Standard Market of the Tokyo Stock Exchange...provides an update on the enrollment of two key ongoing clinical trials for the Company’s developmental compounds MN-166 (ibudilast) and MN-001 (tipelukast), each of which is poised to complete randomization...Specifically, the Company is now down to single digit required randomization in its ongoing Phase 2/3 COMBAT-ALS trial. Concurrently, the Company is seeking the final two randomized subjects for its Phase 2 trial in patients with dyslipidemia and fatty liver disease due to type 2 diabetes....We are actively preparing for regulatory discussions with the FDA, with top-line data anticipated by the end of next year."

P2/3 data • Trial status • Amyotrophic Lateral Sclerosis • Dyslipidemia • Hypertriglyceridemia • Metabolic Dysfunction-Associated Steatohepatitis • Type 2 Diabetes Mellitus

Six promising drug repurposing candidates for Alzheimer's disease and their sex-specific mechanisms and efficacy. (PubMed, Neural Regen Res) - "These included ibudilast, timapiprant, RG2833, diazoxide/ dibenzoylmethane (combined), and BT-11, which targeted key Alzheimer's disease-related molecular pathways such as amyloid-beta plaques, Tau tangles, and neuroinflammation. These drugs, at various stages of development, offer hope for not only managing symptoms but also addressing the underlying mechanisms of Alzheimer's disease. This review underscores the need for a multifaceted approach to Alzheimer's disease treatment, combining symptom relief with disease modification."

Journal • Alzheimer's Disease • CNS Disorders • Inflammation