Asklepios BioPharmaceutical (AskBio)’s AB-1005 (AAV2-GDNF), an investigational adeno-associated viral vector serotype 2 (AAV2) gene therapy, has met its primary end point in 18-month follow-up data from a phase 1b clinical trial (NCT04167540) in patients with Parkinson disease (PD).1
Among 11 patients with PD who were treated in the study, there were no serious adverse events (AEs) attributed to AB-1005 reported at 18 months posttreatment. Furthermore, the neurosurgical delivery procedure for the gene therapy, which involved a 1-time bilateral administration directly to the putamen, was deemed well-tolerated. AskBio noted that the study’s goal of achieving greater than 50% target putamen coverage with the gene therapy was surpassed, with a coverage of 63% (±2%) having been achieved. Follow-up on the occurrence of treatment-related serious AEs for the primary end point will continue for up to 5 years posttreatment as per the clinical trial design. The 11 patients included 6 patients with mild stage PD and 5 patients with moderate stage PD, as assessed by time from diagnosis and baseline severity of symptoms.
“We are encouraged by these early data, which show AB-1005 to be well-tolerated in this study in patients with mild to moderate PD,” Krystof Bankiewicz, MD, PhD, professor and vice chair of research, department of neurological surgery, Ohio State University, and professor emeritus and vice chair of research, University of California – San Francisco, and the cofounder of AskBio subsidiary Brain Neuropathy Bio, said in a statement.1 “Although there is still much to learn about this early-stage investigational gene therapy, these first findings will inform our work in this space and have the potential to contribute to the clinical advancement of AB-1005 for the treatment of Parkinson’s disease.”
Efficacy measures used in the trial include neurological assessments done at 18 months posttreatment, self-report questionnaires focused on symptom severity that were taken at regular intervals, and longitudinal assessment of potential changes in dopamine handling and abnormal metabolic patterns via brain imaging. Brain imaging was also used to longitudinally assess safety. AskBio noted that it expects results from these measurements will be announced in the second quarter of 2024 at a scientific meeting. A phase 2 clinical trial, a design for which has been aligned with feedback from regulatory bodies in the US and Europe, is also anticipated to initiate screening of participants by the middle of this year.
- Asklepios BioPharmaceutical (AskBio)’s AB-1005 (AAV2-GDNF), an investigational adeno-associated viral vector serotype 2 (AAV2) gene therapy, has met its primary end point in 18-month follow-up data from a phase 1b clinical trial (NCT04167540) in patients with Parkinson disease (PD).
- AskBio noted that it expects results from secondary end points will be announced in the second quarter of 2024 at a scientific meeting.
- A phase 2 clinical trial, a design for which has been aligned with feedback from regulatory bodies in the US and Europe, is also anticipated to initiate screening of participants by the middle of this year.
“People living with PD deserve options to address their unmet medical need,” Christian Rommel, PhD, a member of the Executive Committee of Bayer’s Pharmaceuticals Division and Head of Research and Development, added to the statement.1 “The positive outcome of the AB-1005 phase 1b clinical trial is an important step forward in our goal to deliver much-needed treatments in areas where innovation has the potential to make a tremendous impact.”
The phase 1b clinical trial, which is sponsored by Brain Neurotherapy Bio, has assigned patients into 2 cohorts based on whether their PD is mild or moderate stage. The secondary end points, which are all measured at 18 months posttreatment, constitute the changes from baseline in scores for the Movement Disorder Society's Unified Parkinson's Disease Rating Scale and the Non-Motor Symptom Scale, as well as brain dopaminergic cell integrity as assessed by DaTscan SPECT imaging. The study, which originally began in April 2020, was open to patients aged 35 years to 75 years; it is active, but no longer recruiting, with an expected study completion date of June 2027.
AB-1005 is intended to deliver a human glial cell line-derived neurotrophic factor (GDNF) transgene, with the expectation that it will promote survival and morphological differentiation of dopaminergic neurons, the degeneration of which is associated with PD. It is also expected to increase the high-affinity dopamine uptake of these neurons.
In addition to AB-1005, AskBio is also developing gene therapies for indications including limb-girdle muscular dystrophy type 2I/R9 (NCT05230459), Pompe disease (NCT03533673), multiple system atrophy (NCT04680065), and congestive heart failure (NCT04179643), all of which have entered clinical development.2 Furthermore, in August 2022, AskBio announced that its Europe-based subsidiary BrainVectis had received approval from France’s National Agency for Safety of Medicines and Health Products to begin recruiting patients for a phase 1/2 clinical trial of its AAV gene therapy for the treatment of early-stage Huntington disease, BV-101.3
1. AskBio Phase Ib trial of AB-1005 gene therapy in patients with Parkinson’s disease meets primary endpoint. News release. Bayer AG and Asklepios BioPharmaceutical, Inc. January 4, 2024. Accessed January 11, 2024. https://www.bayer.com/media/en-us/askbio-phase-ib-trial-of-ab-1005-gene-therapy-in-patients-with-parkinsons-disease-meets-primary-endpoint/
2.AskBio announces first patient dosed in phase 1 / phase 2 trial of AB-1003 gene therapy for limb-girdle muscular dystrophy type 2I/R9 (LGMD2I/R9). News release. Asklepios BioPharmaceutical, Inc. August 3, 2023. Accessed January 11, 2024. https://www.askbio.com/askbio-announces-first-patient-dosed-in-phase-1-phase-2-lgmd2i-r9/
3. BrainVectis, a subsidiary of AskBio, receives clearance to conduct phase I/II clinical trial in France for its novel gene therapy for early-stage Huntington’s disease. News release. Asklepios BioPharmaceutical, Inc. August 23, 2022. Accessed January 11, 2024. https://www.askbio.com/brainvectis-a-subsidiary-of-askbio-receives-clearance-to-conduct-phase-i-ii-clinical-trial-in-france-for-its-novel-gene-therapy-for-early-stage-huntingtons-disease/