MediciNova completes double-blind phase of COMBAT-ALS ibudilast trial
MediciNova has reached a key procedural milestone in its COMBAT-ALS programme, confirming that the last patient completed their final double-blind visit in the Phase 2b/3 trial of MN-166 (ibudilast) for amyotrophic lateral sclerosis. The La Jolla-based company said it expects to report topline results from the controlled portion of the study before the end of 2026.
A total of 234 participants were randomised across sites in the United States and Canada. Those still active in the programme are now receiving MN-166 in a six-month open-label extension, with the final last-patient, last-visit for the whole study projected for March 2027. The immediate next step is database lock and formal statistical analysis.
Trial design and endpoints
COMBAT-ALS is a randomised, double-blind, placebo-controlled study evaluating MN-166 over a 12-month treatment period. The primary endpoint is the Combined Assessment of Function and Survival (CAFS), a composite measure that captures both functional decline and mortality. Secondary endpoints include the ALS Functional Rating Scale-Revised (ALSFRS-R), hand-held dynamometry for muscle strength, and quality-of-life assessments. The breadth of the endpoint package reflects the complexity of measuring disease modification in ALS, where regulatory agencies expect multi-dimensional evidence before granting approval.
MN-166 is a small-molecule PDE4 inhibitor that also suppresses macrophage migration inhibitory factor (MIF) and other inflammatory cytokines. The compound carries both FDA Fast Track and Orphan Drug designations, as well as EMA orphan designation, which accelerate regulatory dialogue and provide commercial incentives if approval is ultimately obtained.
Yuichi Iwaki, President and Chief Executive Officer of MediciNova, said the milestone "keeps us on track to report topline results by the end of 2026" and described the trial as having "the potential to provide important insight into MN-166 as a treatment option for people living with ALS, a disease with substantial unmet medical need."
Market context and competitive landscape
ALS remains one of the most challenging and commercially underserved areas in neurology. Riluzole, approved in 1995, and AMX0035 (Relyvrio, developed by Amylyx Pharmaceuticals) have been the principal disease-modifying options in recent years, though Amylyx voluntarily withdrew Relyvrio from the US market in 2024 after a confirmatory trial failed to demonstrate benefit, reopening the question of what the standard of care should look like. Tofersen (Qalsody), an antisense oligonucleotide targeting SOD1-ALS, gained FDA accelerated approval for a genetically defined patient subset, illustrating the agency's willingness to use surrogate endpoints in the indication.
MediciNova's neuroinflammation mechanism differentiates MN-166 from these approaches mechanistically, but the field remains sceptical of neuroinflammation as a monotherapy target without clear biomarker stratification. The company reported a higher proportion of treatment responders in earlier Phase 1/2 and Phase 2 work, though no hazard ratios or responder definitions were provided in the current release. Investors will want to see whether COMBAT-ALS was adequately powered and whether any pre-specified subgroup analyses accompany the topline readout.
Beyond ALS, MediciNova is developing MN-166 across progressive multiple sclerosis, degenerative cervical myelopathy, glioblastoma, Long COVID, and substance use disorder, giving the compound a wide but clinically heterogeneous portfolio footprint. A positive COMBAT-ALS readout before year-end could materially re-rate the stock and open licensing conversations; a negative result would put pressure on the broader MN-166 thesis given the compound's centrality to the pipeline.