MDS Congress 2026: Late-Breaking Data Snapshot

The 2026 International Congress of Parkinson's Disease and Movement Disorders (MDS Congress), held October 4-8 in Seoul, South Korea, closed with a slate of late-breaking abstracts spanning Parkinson disease (PD), atypical parkinsonism, Huntington disease (HD), and Tourette syndrome. Rather than sift through all of them, this snapshot pulls 10 of the most clinically relevant, with an emphasis on phase 2 and 3 readouts and agents with novel mechanisms.

The headline story was a split verdict. Two genetically targeted disease-modification programs, LRRK2 inhibition and GCase activation, came up empty in phase 2b, while a non-dopaminergic symptomatic therapy cleared phase 3. Earlier-stage data on a LRRK2 degrader, a paraoxonase activator, and a brain-penetrant GLP-1/GIP agonist kept the pipeline interesting, and long-term extensions in HD chorea and Tourette syndrome added durability data clinicians can use now.

Solengepras Cuts OFF Time in Pivotal Phase 3 ARISE Trial

ARISE was a 12-week, randomized, double-blind, placebo-controlled phase 3 trial of solengepras (Cerevance), an oral, brain-penetrant GPR6 inhibitor that acts on the indirect pathway rather than on dopamine receptors. A total of 341 patients with PD and at least 3 hours of daily OFF time on stable background therapy were randomized 1:1:1 to solengepras 75 mg, 150 mg, or placebo once daily.¹

In topline results reported by Cerevance ahead of the presentation, solengepras 150 mg reduced daily OFF time by an additional 0.61 hours (about 37 minutes) vs placebo at week 12 (P = .035) in a population averaging 5.65 hours of OFF time per day. The 150-mg dose also improved the key secondary end point of ON time without troublesome dyskinesia. Discontinuations due to adverse events were 3.5% across groups, with no serious adverse events at 150 mg.²

LRRK2 Inhibitor BIIB122 Misses Primary End Point in Phase 2b LUMA

LUMA tested BIIB122/DNL151 (Biogen/Denali Therapeutics), an oral, CNS-penetrant LRRK2 kinase inhibitor, in 648 patients with early-stage PD (diagnosis within 2 years). Participants received 225 mg once daily or placebo for 48 to 144 weeks, with the primary end point of time to confirmed worsening of at least 6 points on modified MDS-UPDRS Parts II and III.³

BIIB122 showed no benefit on the primary end point (HR, 1.04; 95% CI, 0.85-1.28; P = .4538) or on any secondary end point. Target engagement was clear, with more than 90% reduction in whole-blood pS935 LRRK2 and a roughly 30% peak reduction in CSF pRab10. Headache was more common with BIIB122 (17.1% vs 9.2%), and adverse events led to drug withdrawal in 11.2% vs 4.6% with placebo.

GCase Activator BIA 28-6156 Fails to Slow GBA-PD in Phase 2b ACTIVATE Trial

ACTIVATE evaluated BIA 28-6156 (Bial), an oral, small-molecule allosteric activator of beta-glucocerebrosidase (GCase), in 272 patients with GBA1-associated PD and 1 to 7 years of disease duration. Patients were randomized to 10 mg/day, 60 mg/day, or placebo for 78 weeks.

Neither dose delayed time to clinically meaningful progression, defined as at least a 2-point increase on MDS-UPDRS Part II (HR, 1.0 for both doses; P = .82 for 60 mg and P = .90 for 10 mg). The key secondary end point of at least 5-point worsening on Part III was also negative, and exploratory analyses showed no dose response. The drug was well tolerated, and investigators framed the results as a lesson in the end point challenges of targeting GCase.⁴

PROTAC LRRK2 Degrader ARV-102 Shows Early Biomarker and Oculomotor Signals

ARV-102 (Arvinas) is a first-in-class PROteolysis TArgeting Chimera (PROTAC) that degrades LRRK2 through the ubiquitin-proteasome system, rather than inhibiting its kinase activity. In the multidose part of this phase 1 study, 24 patients with PD were randomized to ARV-102 20, 40, or 80 mg or placebo daily for 28 days.⁵

ARV-102 improved saccadic hypometria, an eye-movement marker of basal ganglia dysfunction, vs placebo. MDS-UPDRS Part III worsened by 4.8 points with placebo compared with 2.2, 1.6, and 0.8 points across the 20-, 40-, and 80-mg groups. CSF markers of endolysosomal dysfunction and neuroinflammation (CD68, GPNMB) fell, synaptic markers (NPTX2, CBLN4) rose, and the degree of CSF LRRK2 reduction correlated with both CD68 change (R = 0.72) and oculomotor improvement.

First-in-Class PON Activator Vutiglabridin Improves Motor Scores in Early PD

Vutiglabridin (Glaceum) is a novel paraoxonase (PON) activator with neuroprotective effects in preclinical PD models. In this multicenter, double-blind phase 2a trial, 99 patients with newly diagnosed PD were randomized to 400 mg, 800 mg, or placebo daily for 24 weeks, followed by a 4-week washout.

At week 24, MDS-UPDRS Part III scores improved by 1.37 points with 400 mg and 2.83 points with 800 mg, while placebo worsened by 0.73 points. The 3.56-point difference between 800 mg and placebo was significant (P = .03) in the per-protocol population (n = 77). The 800-mg group trended toward increased serum PON1 activity, and there were no drug-related serious adverse events.⁶

Brain-Penetrant GLP-1/GIP Agonist KP405 Moves Neuronal Biomarkers in Phase 1

KP405 (Kariya Pharmaceuticals) is a first-in-class, brain-penetrating dual GLP-1/GIP receptor agonist designed for PD, building on prior GLP-1 data with exenatide and lixisenatide. In a placebo-controlled phase 1 study, healthy older adults and patients with PD (8 per cohort, 6:2 active to placebo) received 7 days of subcutaneous treatment.

Exploratory analysis of brain-derived extracellular vesicles from plasma showed increases in insulin signaling and neuroprotection scores and decreases in neuroinflammation scores with KP405, while placebo values stayed near baseline. Effects generally returned toward baseline by follow-up, and alpha-synuclein levels fell on day 1 in the healthy older cohort. The data are small and exploratory but offer an early read on target engagement in the brain.⁷

GV1001 Shows Durable Signal in PSP Through 72 Weeks

GV1001 (GemVax & KAEL), a synthetic hTERT-derived peptide that modulates neuroinflammation, was evaluated in a 48-week open-label extension after a 24-week, double-blind phase 2a trial in progressive supranuclear palsy (PSP). All 67 participants received GV1001 1.12 mg during the extension, regardless of their original assignment (0.56 mg, 1.12 mg, or placebo).

There were no new safety signals and no drug-related serious adverse events through week 72. PSP Rating Scale trajectories continued to diverge, with patients who started on 0.56 mg faring best and former placebo patients faring worst, suggesting a benefit from early treatment. In a matching-adjusted indirect comparison, the early 0.56-mg group worsened by 3.31 points at week 72 vs 10.66 points at week 52 in external placebo controls (P < .0001), and investigators now call for a phase 3 trial focused on PSP-Richardson syndrome and low-NfL patients.⁸

Phase 3 MASCOT Trial of Amlenetug in MSA Completes Enrollment

Amlenetug (Lundbeck) is an IgG1 monoclonal antibody against aggregated alpha-synuclein, designed to block pathological seeding and spread in multiple system atrophy (MSA). Although the phase 2 AMULET trial missed its primary end point, consistent clinical and biomarker signals supported MASCOT, a 72-week, placebo-controlled phase 3 trial with intravenous dosing every 4 weeks.⁹

MASCOT randomized 401 patients, of whom 61% had MSA-C and 39% had MSA-P, with a mean age of 60.9 years and mean symptom duration of 3.2 years. Baseline UMSARS total score averaged 33.9, and most patients (54.3%) were rated moderately impaired. MASCOT is the first phase 3 trial of an anti-alpha-synuclein antibody aimed at slowing MSA progression, with results expected in Q3 2027.

Valbenazine Maintains HD Chorea Control Through 5 Years

KINECT-HD2 is a 5-year, open-label study of once-daily valbenazine (Neurocrine Biosciences; up to 80 mg) in 154 adults with HD chorea, making it the longest prospective evaluation of a VMAT2 inhibitor for any condition. Median exposure was 980 days, with some patients treated for up to 1803 days.

From a baseline Total Maximal Chorea (TMC) score of 12.0, mean improvements were 5.7 points at week 50, 5.1 points at week 104, and 3.4 points at week 208. Chorea returned to near baseline after discontinuation (change of -0.8). The most common adverse events were fall (45.5%), somnolence (26.0%), and fatigue (21.4%), consistent with HD itself and prior VMAT2 inhibitor trials.¹⁰

Ecopipam Sustains Tic Reduction in Long-Term Tourette Extension

Ecopipam (Teva), a first-in-class selective dopamine D1 receptor antagonist, is being studied in a 36-month open-label extension in children, adolescents, and adults with Tourette syndrome. This interim analysis at 27 months included 118 treated participants, 83% of whom were under age 18, with a target dose of 1.8 mg/kg/day.

Yale Global Tic Severity Scale Total Tic Score fell by 12.0 points (40.1%) at month 12 and 13.9 points (45.6%) at month 18 from a baseline of 28.1 (both P < .0001). Weight gain was reported in only 3.4% of participants, there were no drug-induced movement disorders, and 3.4% discontinued due to adverse events, a profile that contrasts with the metabolic burden of D2-blocking antipsychotics.¹¹

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REFERENCES
1. Hauser R, Sarva H, Karbowniczek A, et al. Results from ARISE: a pivotal phase 3 trial of solengepras in Parkinson's disease with motor fluctuations. Presented at: International Congress of Parkinson's Disease and Movement Disorders; October 4-8, 2026; Seoul, South Korea. Abstract LBA 21.
2. Cerevance announces positive phase 3 ARISE results: once-daily oral solengepras meets primary endpoint and demonstrates motor and non-motor benefits in Parkinson's disease. News release. Cerevance. October 7, 2026.
3. Llorens Arenas R, Siderowf A, Lang A, et al. Results from a phase 2b, placebo-controlled study to determine the efficacy and safety of BIIB122/DNL151 in participants with early-stage Parkinson's disease. Presented at: International Congress of Parkinson's Disease and Movement Disorders; October 4-8, 2026; Seoul, South Korea. Abstract LBA 19.
4. Ferreira J, Fernandez HF, Poewe WP, et al. Efficacy and safety of the GCase activator BIA 28-6156 in GBA-associated Parkinson's disease: results from the phase 2b ACTIVATE trial. Presented at: International Congress of Parkinson's Disease and Movement Disorders; October 4-8, 2026; Seoul, South Korea. Abstract LBA 18.
5. Fraser K, van de Bult L, Smits L, et al. Phase 1 study of ARV-102, a PROTAC LRRK2 degrader, in Parkinson's disease: oculomotor and biomarker data. Presented at: International Congress of Parkinson's Disease and Movement Disorders; October 4-8, 2026; Seoul, South Korea. Abstract LBA 15.
6. Oh Y, Cho JW, Baik JS, et al. A multicenter, double-blind, randomized, placebo-controlled, phase 2a clinical trial of vutiglabridin in early-stage Parkinson's disease. Presented at: International Congress of Parkinson's Disease and Movement Disorders; October 4-8, 2026; Seoul, South Korea. Abstract LBA 22.
7. Eitan E, Laquian I, Connell J, Thomsen M. Evaluating KP405, a CNS-penetrating GLP1/GIP analogue, in a randomized, placebo-controlled phase I study in healthy elderly participants and Parkinson's disease patients with exploratory analysis of biomarkers in brain-derived extracellular vesicles. Presented at: International Congress of Parkinson's Disease and Movement Disorders; October 4-8, 2026; Seoul, South Korea. Abstract LBA 23.
8. Lee JY, Kim HJ, Ahn TB, et al. 72-week safety and efficacy of GV1001 in progressive supranuclear palsy: phase 2a open-label extension results. Presented at: International Congress of Parkinson's Disease and Movement Disorders; October 4-8, 2026; Seoul, South Korea. Abstract LBA 1.
9. Kjærsgaard L, Schiavon Krabbe M, Berger AK, et al. Baseline characteristics of a phase 3 double-blind, randomized trial of amlenetug for the treatment of multiple system atrophy. Presented at: International Congress of Parkinson's Disease and Movement Disorders; October 4-8, 2026; Seoul, South Korea. Abstract LBA 2.
10. Mehanna R, Furr Stimming E, Kayson E, et al. Long-term safety and efficacy of once-daily valbenazine in Huntington's disease chorea: results from the 5-year KINECT-HD2 study. Presented at: International Congress of Parkinson's Disease and Movement Disorders; October 4-8, 2026; Seoul, South Korea. Abstract LBA 4.
11. Gilbert DL, Black KJ, Kompoliti K, et al. Long-term safety and effect of ecopipam, a selective dopamine D1 receptor antagonist, in children, adolescents, and adults with Tourette syndrome. Presented at: International Congress of Parkinson's Disease and Movement Disorders; October 4-8, 2026; Seoul, South Korea. Abstract LBA 9.