Risvodetinib (c-Abl), Phase 2 "201"

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

Inhibikase Therapeutics developed the drug; the registry sponsor is now ABLi Therapeutics (launched May 2025), which presented the final results at the Movement Disorders Society Congress on 5 October 2025. Paper: Werner et al., Nature Aging 2026;6:626-635 (online 20 Feb 2026).

What happened

c-Abl is an enzyme that may switch on in stressed dopamine neurons and drive synuclein clumping and mitochondrial damage. The first c-Abl drugs, nilotinib and vodobatinib, failed (landmark 68); nilotinib barely entered the brain. Risvodetinib was designed to get in.

• Design. Phase 2a, randomised, double-blind, placebo-controlled, NCT05424276, started 15 May 2023. Untreated early Parkinson's, 12 weeks, 50, 100 or 200 mg once daily versus placebo. 137 participants (35, 34, 33 and 35 per arm) in both the paper and the registry; the company release says 126. The trial was not powered for efficacy.
• Primary result. Safety and tolerability: met. Adverse events were similar to placebo and 95% completed dosing.
• Efficacy. 14 secondary measures were tested in a fixed order. The first, MDS-UPDRS parts II + III, did not reach significance (registry: difference from placebo −0.77, +0.97 and +1.27 points at 50, 100 and 200 mg; P = 0.69, 0.61 and 0.51). Part II alone was better than placebo at 100 mg (difference −1.41, 95% CI −2.72 to −0.10, P = 0.036, nominal, uncorrected) but not at 50 or 200 mg; this came mostly from placebo worsening (+1.09) rather than drug-treated people improving. The Schwab and England daily-living scale was nominally significant at 50 mg only. Part III (motor exam) was numerically worse than placebo at 100 and 200 mg (+2.4 points, P about 0.16).
• Exploratory. Less phosphorylated synuclein in skin biopsies at all doses, and in blood and spinal fluid in a company biomarker analysis (August 2026 release; no peer-reviewed data yet).
• Related. Radotinib, another c-Abl drug (Il-Yang, South Korea), is in a 43-person Phase 2 (NCT04691661): active, not recruiting; primary completion September 2026, completion April 2027.

Why it moved us toward a cure

It is the first test of a c-Abl drug that reaches the brain. The safety is good, but 12 weeks is too short and the study too small to show slowing, and the efficacy hints are not corrected for multiple testing. ABLi describes planned longer trials (BASE, ABILITY, CAMPD) and a Michael J. Fox Foundation platform collaboration, but none has registered results.

It was designed to enter the brain better than nilotinib, which barely did (landmark 322).

Outcome

Open, not resolved. The class has not yet had a proper longer, larger slowing test.

Sources

• Werner et al., Nat Aging 2026;6:626-635, DOI 10.1038/s43587-026-01084-4, PMID 41721133 (abstract via Europe PMC)
• ClinicalTrials.gov NCT05424276 (API, 19 Oct 2026; results posted 19 Nov 2025) · radotinib NCT04691661
• ABLi release, 9 Oct 2025 (BioSpace) · ABLi biomarker release, 4 Aug 2026 · NeurologyLive, 5 Oct 2025
• Not yet verified: the paper's full text (only the abstract and registry results were read); the skin-biopsy numbers; the planned BASE, ABILITY and CAMPD trials and the Foundation agreement (company statements; not registered); whether Inhibikase paused Parkinson's work (not confirmed).