UB-312 Reduces α-Synuclein in Parkinson Disease in Phase 1 Trial

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New findings from a phase 1 trial presented at AD/PD 2024 showed that UB-312 antibodies decrease α-synuclein levels in the cerebrospinal fluid of patients with Parkinson disease.

Jean-Cosme Dodart, PhD, senior vice president of research at Vaxxinity

Jean-Cosme Dodart, PhD

Credit: Vaxxinity

In new data from a randomized, double-blind, placebo-controlled phase 1 clinical trial (NCT04075318), findings showed that antibodies derived from UB-312 (Vaxxinity), an investigational immunotherapeutic, reduced the pathological α-synuclein (α-Syn) in cerebrospinal fluid (CSF) of patients with Parkinson disease (PD).1

Among 20 patients with PD, UB-312-induced antibodies showed preferential binding to aggregated α-Syn and almost no binding to normal monomeric α-Syn, as measured by dot blot. Following a single priming regimen, patients treated with UB-312 in the 300/100/100 µg dosing group showed a 20% decrease from baseline in aggregated α-Syn in the CSF compared with a 3% increase in the placebo group (P <.05), as measured by a seed amplification assay.

Top Clinical Takeaways

  • UB-312 antibodies demonstrated efficacy in reducing aggregated α-synuclein in the cerebrospinal fluid (CSF) of patients with Parkinson disease.
  • Patients with detectable UB-312-induced antibodies in their CSF showed improvements in daily living activities.
  • The phase 1 trial suggests that UB-312 is well-tolerated and holds promise as a disease-modifying therapy for PD.

“Currently, there are no treatments that address the underlying conditions of Parkinson, and we are very excited about this target engagement data. This provides us [with the] confidence that we are going after the right target and in a way that is statistically and clinically relevant to patients. There is new hope on the horizon,” Jean-Cosme Dodart, PhD, senior vice president of research at Vaxxinity, said in a statement.1 “With Parkinson being the fastest growing neurodegenerative disease in the world, Vaxxinity remains committed to developing safe, convenient, and effective disease-modifying active immunotherapies for all.”

READ MORE: Phase 1 Data Highlights Sustained Efficacy of Cell Therapy Bemdaneprocel in Parkinson Disease

The phase 1 trial of UB-312, conducted at the Centre for Human Drug Research in the Netherlands, consisted of 2 parts. Following Part A, Part B explored the safety, tolerability, and immunogenicity by using 2 doses of UB-312 compared with placebo in 20 age-matched patients with early PD for 20 weeks, followed by observation for 24 weeks. These results, presented at the 2024 International Conference on Alzheimer’s and Parkinson’s Disease (AD/PD), held March 5-9 in Lisbon, Portugal, by Dodart, come from Part B. The study is a The Michael J. Fox Foundation funded 2-year collaborative project between Vaxxinity, the Mayo Clinic, and UTHealth Houston to assess CSF collected from patients, and conduct exploratory research to explore target engagement.

In a post hoc analysis of the trial, investigators observed that patients with detectable UB-312-induced antibodies in the CSF showed improvement in activities of daily living as measured by the Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) II clinical scale (P <.01). According to a statement, these results also suggest an association between reduction in aggregated α-Syn in the brain and change in MDS-UPDRS II (R = .52, P = .001).1 Additionally, findings suggest UB-312 demonstrated tolerability, with most adverse events reported as mild and transient, and immunogenic, with antibodies detectable in serum and CSF.

“What we see from our UB-312 program is the potential to change the whole conversation around Parkinson treatment and prevention,” Lou Reese, MBA, cofounder and executive chairman at Vaxxinity, said in a statement.1 “Our findings suggest UB-312 could transform Parkinson care, offering hope for improved outcomes with a disease-modifying treatment. The future isn’t decades away: today’s patients with PD may have hope for the near, not distant future.”

Part A of the trial investigated the safety, tolerability, and immunogenicity of the UB-312 vaccine in healthy participants.2 Among 50 healthy participants enrolled, 23 received all three intramuscular doses of UB-312 at weeks 1, 5, and 13 (doses ranging between 40 and 2000 μg). In the participants receiving the 300/300/300 μg UB-312 dose regimen, antibodies were detectable in serum and CSF (average CSF/serum ratio, 0.2%). For further evaluation, the 100- and 300-μg doses were selected for participants with PD. These results, published in Movement Disorders, suggest that the vaccine is highly immunogenic as all patients dosed with it showed detectable anti-α-Syn antibodies in both serum and CSF.

REFERENCES
1. Vaxxinity Announces Positive Target Engagement Data from Phase 1 Clinical Trial for Parkinson’s Disease at AD/PD™ 2024. News Release. Published March 7, 2024. Accessed March 14, 2024. https://ir.vaxxinity.com/news-releases/news-release-details/vaxxinity-announces-positive-target-engagement-data-phase-1
2. Vaxxinity Announces UB-312 Successfully Met Primary Objectives of Phase 1 Clinical Trial in Parkinson’s Disease. News Release. Vaxxinity. Published June 22, 2023. Accessed March 14, 2024. https://www.globenewswire.com/en/news-release/2023/06/22/2692878/0/en/Vaxxinity-Announces-UB-312-Successfully-Met-Primary-Objectives-of-Phase-1-Clinical-Trial-in-Parkinson-s-Disease.html
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