AskBio's AB-1005 Gene Therapy Shows Promise in Parkinson's Disease Phase Ib Trial
Key Insights
AskBio presented 18-month Phase Ib trial results for AB-1005, a gene therapy for Parkinson's disease (search), at the American Academy of Neurology 2024 Annual Meeting.
The trial met its primary objective, demonstrating that a one-time bilateral delivery of AB-1005 directly to the putamen was well tolerated in patients.
The moderate PD cohort showed significant improvements in motor function, while the mild cohort demonstrated relative clinical stability over the 18-month period.
Bayer and its subsidiary Asklepios BioPharmaceutical (AskBio) have announced positive data from their Phase Ib clinical trial of AB-1005, a gene therapy targeting Parkinson's disease (search) (PD). The multi-center, non-randomized study, involving 11 PD patients, assessed the safety and clinical impact of a one-time bilateral convection-enhanced delivery of AB-1005 to the putamen.
Safety and Tolerability
The study met its primary objective, demonstrating that AB-1005 was well-tolerated. As of November 3, 2023, 57 nonserious adverse events (AEs) and six serious adverse events (SAEs) were reported, with most AEs being transient and expected perioperative events. Importantly, the bilateral infusions of AB-1005 within the putamen were found to be well tolerated, with no SAEs linked to the gene therapy or contrast agent.
Clinical Impact on Mild and Moderate PD
Patients were divided into two cohorts based on the stage of their PD: mild (six patients) and moderate (five patients). The Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) was used to assess the severity of PD symptoms.
The mild cohort showed relative stability from baseline to 18 months in both MDS-UPDRS Part II (Activities of Daily Living) and Part III (Motor Examination) scores, in both 'ON' and 'OFF' medication states. However, patient-reported PD Motor Diaries showed a -1.3 hour reduction in “Good ON” time, a 0.2 hour rise in “ON” time with troublesome dyskinesia, and a 1.1 hour rise in “OFF” time.
In contrast, the moderate cohort exhibited significant improvements. MDS-UPDRS scores demonstrated a Part II Activities of Daily Living mean improvement of -3.8 points from baseline, and Part III Motor Examination improvements of -20.4 points 'OFF' medication and -10.6 points 'ON' medication compared to baseline. Motor Diaries for the Moderate Cohort reported a 2.2-hour improvement in “Good ON” state time, a 0.5-hour reduction in “ON” state with troublesome dyskinesia, and a 1.7-hour reduction in “OFF” state time.
Upcoming Phase II Trial
Based on these results, a REGENERATE PD Phase II trial is scheduled to begin subject enrolment in the US, EU, and UK later this year. Krystof Bankiewicz, MD, PhD, Scientific Chair, Parkinson’s and MSA, AskBio, stated, “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. 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.”
About AB-1005
AB-1005 (also known as AAV2-GDNF (search)) is an investigational gene therapy based on adeno-associated viral vector serotype 2 (AAV2) containing the human glial cell line-derived neurotrophic factor (GDNF) transgene, which allows for stable and continuous expression of GDNF in localized regions of the brain after direct neurosurgical injection with magnetic resonance imaging (MRI)-monitored convection enhanced delivery.