Vodobatinib: PROSEEK Phase 2

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

Sun Pharma Advanced Research Company (SPARC); lead authors Harini Sarva, Rajesh Pahwa and Orest Hurko, with Jorge Hernandez-Vara, Stewart Factor and others. NCT03655236.

What happened

• Why this drug. Nilotinib barely reached spinal fluid (landmark 322). Vodobatinib is a more potent c-Abl blocker (laboratory IC50 0.9 nM against 15 to 45 nM for nilotinib). In earlier safety work, doses of 192 and 384 mg gave spinal-fluid levels above the level needed to inhibit c-Abl.
• Design. Phase 2, randomised, double-blind, placebo-controlled, 513 people aged 50 or over with early Parkinson's (Hoehn and Yahr stage 2 or less, not on dopamine drugs). They received 384 mg, 192 mg or placebo once daily; main measure was change in MDS-UPDRS part III (the motor exam) at week 40, with an optional extension. Registry: start 18 Feb 2019; terminated; primary completion 8 April 2024.
• Result. On 10 April 2024 SPARC said an interim analysis of 442 people who completed 40 weeks showed no superiority over placebo, and closed the study. SPARC also said the placebo response looked unusually good. In the published results mean change was +1.0 (384 mg), +1.5 (192 mg) and -1.0 (placebo); a higher score means worse. Both doses favoured placebo.
• Dropout rose with dose, and blood neurofilament light chain (a marker of nerve damage) rose in both drug groups. The authors judged the drug ineffective in this population.

Why it moved us toward a cure

It tested c-Abl blockade properly: the drug reached the brain at the intended level and still did not slow the motor exam. This leaves the idea resting on newer drugs (landmark 174, 219). The origin of the idea is in landmark 68.

Outcome

Dead end for vodobatinib at the doses tested.

Sources

• Sarva et al., "Evaluation of c-Abl inhibitor vodobatinib in subjects with early Parkinson's disease," npj Parkinson's Disease 2026;12, DOI 10.1038/s41531-026-01275-1 (citation via Weill Cornell listing; doses and secondary numbers via ReachMD summary)
• ClinicalTrials.gov NCT03655236 (results posted; API v2, 19 Oct 2026)
• SPARC interim result, 10 Apr 2024
• Walsh et al., Parkinsonism Relat Disord 2023;108:105281, DOI 10.1016/j.parkreldis.2023.105281 (Europe PMC)
• Not yet verified: the paper's full text (not opened); why registry-reported completers (300 at week 40) differ from SPARC's 442 interim completers; the extension results.