Parkinson Gene Therapy Shows Stability, Some Improvements in ON/OFF Time Disease Measures


Based on these data, the phase 2 Regenerate PD trial of AB-1005 will begin enrolling later this year.

Krystof Bankiewicz, MD, PhD, Scientific Chair, Parkinson’s and MSA, AskBio

Krystof Bankiewicz, MD, PhD

Credit: The Stem Cellar

A phase 1b clinical trial (NCT04167540) of AAV2-GDNF gene therapy (AB-1005; Asklepios Biopharmaceutical) met its primary safety and efficacy endpoints at 18 months, showing stability in disease markers in participants with mild to moderate Parkinson disease (PD).1

Data from the trial were presented at the 2024 American Academy of Neurology (AAN) Annual Meeting, held April 13-18, in Denver, Colorado, by Amber D. Van Laar, MD, vice president, clinical development, Brain Neuropathy Bio, AskBio. AB-1005 is an investigational adeno-associated virus (AAV2) gene therapy containing the human glial cell line-derived neurotrophic factor (GDNF) transgene.

“These early findings are encouraging and show AB-1005 to be well tolerated in this study in patients with mild to moderate Parkinson’s disease,” Krystof Bankiewicz, MD, PhD, Scientific Chair, Parkinson’s and MSA, AskBio, said in a statement.2 “Further, they highlight areas of potential future exploration in our upcoming Phase II REGENERATE PD trial, which will look more closely at the potential efficacy of AB-1005 in the treatment of Parkinson’s disease.”

Van Laar presented data from 11 participants with follow-up of at least 18 months that have been enrolled in the trial as of November 3, 2023. These participants, in a mild PD cohort (n = 6) and a moderate PD cohort (n = 5), received bilateral intraputaminal infusions of AB-1005 up to 1.8 mL. The infusions 1005 resulted in putamen coverage of 63% (±2%), exceeding the 50% coverage goal. There was asymptomatic unilateral T1 hypointensity adjacent to 3 of the putaminal infusion trajectories and 5-year clinical follow-up is ongoing.1

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The procedure and therapy were well-tolerated, with no related serious adverse events (AEs).1 Treatment-emergent AEs included headache, tremor, dyskinesia, arthralgia, musculoskeletal chest pain, fatigue, COVID-19, and magnetic resonance imaging (MRI) abnormalities. There have been 6 unrelated serious AEs in 3 participants, 2 in the moderate cohort and 1 in the mild cohort.

“Multiple clinical trials with growth factors have been performed in PD with mixed results; complexity of central nervous system delivery has been a significant limitation to date​,” Van Laar said during her presentation.1

Efficacy outcomes at 18 months were measured by Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), patient-reported PD Motor Diaries, and Levodopa Equivalent Daily Dose (LEDD).

The mild cohort demonstrated relative stability from baseline to 18 on Activities of Daily Living scores and Motor Examination scores in “ON” and “OFF” medication states on MDS-UPDRS. The moderate cohort had a mean improvement of 3.8 (standard error [SE], 3.5) on Activities of Daily Living from baseline and of 20.4 points (SE, 4.5) “OFF” medication and 10.6 points (SE, 3.6) “ON” medication compared to baseline. A 3-point reduction is considered meaningful and the 20.4-point improvement considered a large clinical effect.1

With the motor diaries, the mild cohort had a 1.3-hour reduction in “Good ON” time, a 0.2-hour increase in “ON” time with troublesome dyskinesia, and a 1.1-hour increase in “OFF” time. Potential confounding factors include 1 participant declining to complete the diary after dosing and another with a genetic defect of unknown pathological significance that drove troublesome dyskinesia and increased “OFF” state time. In the moderate cohort, there was a clinically meaningful 2.2-hour improvement in “Good ON” state time (23.6% ±11.8%); a 0.5-hour reduction in “ON” state with troublesome dyskinesia; and a 1.7-hour reduction in “OFF” state time (33.1% ±17.4) at 18 months.1

Looking at LEDD, the mild cohort had a lower LEDD at baseline than the moderate cohort and was stable through 18 months. The moderate cohort had a mean 258 ± 162 mg LEDD reduction from baseline, with a progressive reduction of dopaminergic medications post-treatment, specifically with a reduced levodopa requirement.1

“We are excited to see AskBio’s investigational gene therapy for Parkinson’s disease reach significant milestones in clinical development and look forward to moving into Phase II later this year,” Christian Rommel, PhD, Head of Research and Development, Pharmaceuticals Division, Bayer, added.2 “While much remains to be done, we recognize with increasing confidence the potential of AB-1005 to provide a transformative impact for patients in the future.”

AskBio will publish full 18-month data later in 2024 and will begin enrolling in the phase 2 Regenerate PD trial of AB-1005 in the United States, European Unions, and the United Kingdom later this year.​

1. Van Laar AD, Christine CW, Merola A, et al. Phase 1b Safety and Preliminary Efficacy of Bilateral Intraputaminal Delivery of AAV2-GDNF (AB-1005) in Participants With Mild or Moderate Parkinson’s Disease​. Presented at: 2024 AAN Annual Meeting, April 13-18; Denver, Colorado.
2. AskBio presents 18-month Phase Ib trial results of AB-1005 gene therapy for patients with Parkinson’s disease. News release. AskBio. April 16, 2024.
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