AskBio Makes Progress in Clinical Evaluation of Parkinson Disease Gene Therapy AB-1005
The company has begun the process of randomly assigning enrolled participants in the sham-controlled phase 2 REGENERATE-PD trial.
Asklepios BioPharmaceutical(AskBio) has begun the process of randomly assigning enrolled participants in the sham-controlled phase 2 REGENERATE-PD clinical trial (NCT06285643) evaluating AB-1005 (AAV2-GDNF), an investigational adeno-associated virus vector serotype 2 (AAV2) gene therapy, for the treatment of Parkinson disease (PD).1
The randomized, double-blind study began recruitment activities in the United States in 2024. It is open to patients with moderate-stage PD aged from 45 to 75 years. The trial, which will take place in Germany, Poland, and the United Kingdom in addition to the US, is expected to enroll an estimated 87 patients in total.
“The randomization of the first participants in REGENERATE-PD is positive news for people living with PD and the physicians treating them,” principal investigator Rajesh Pahwa, MD, the director of the Parkinson’s Disease and Movement Disorder Center at University of Kansas Medical Center, said in a statement.1 “There is a significant need for neurorestorative therapies in PD and seeing the advancement of an important investigational gene therapy in a phase 2 clinical trial gives hope to patients and the medical community.”
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.2,3 It is administered via a direct neurosurgical injection with MRI-monitored convection enhanced delivery and is also expected to increase the high-affinity dopamine uptake of the neurons in question.
Patients in the experimental arm of REGENERATE-PD will receive a bilateral image-guided infusion into the putamen of a single dose of AB-1005, while patients in the sham comparator arm will undergo a control surgical procedure consisting of bilateral partial burr/twist holes without dural penetration. CGTLive® previously covered the design of the clinical trial in-depth, shortly before its initiation on June 11, 2024.
AB-1005 has previously been evaluated a phase 1b clinical trial (NCT04167540) for patients with PD. The phase 1b trial reached its primary completion date on October 17, 2023, and is no longer recruiting new participants, but long-term follow-up is ongoing. Data from the phase 1b trial was most recently presented at the International Congress of Parkinson’s Disease and Movement Disorders, held in Philadelphia, PA, from September 27 to October 1, 2024.1 AskBio highlighted that at 36 months posttreatment the data showed trends for improvement in patients in the moderate PD cohort on the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and motor diaries. At the same time point, patients in this cohort also demonstrated trends for reductions in Parkinson’s medications (levodopa-equivalent daily dose [LEDD]). Furthermore, the company stated that the majority of patients in this cohort had an “overall stable clinical status”—not much change was seen on the MDS-UPDRS, self-reported PD motor diary, or LEDD for these patients. With regard to safety, AskBio reported that the gene therapy was well-tolerated and that no serious adverse events were deemed related to AB-1005 itself.
“AskBio continues to mark significant milestones in the clinical development of the investigational gene therapy AB-1005 as we strive to bring a safe and effective gene therapy to patients with moderate stage PD,” Canwen Jiang, MD, PhD, the chief development officer and chief medical officer of AskBio, added to the statement.1 “With REGENERATE-PD participants now being randomized, we are excited by our progress with AB-1005 and look forward to sharing further updates at an appropriate scientific forum as the program advances through next year and beyond.”
CGTLive’s sister site, NeurologyLive®, previously spoke with Russell Lonser, MD, director for the Gene Therapy Institute and chair of the department of neurological surgery at The Ohio State University, about AB-1005 in May 2024.4 Lonser spoke about the most recent data available at the time and the potential implications of gene therapy advancements for the future treatment landscape of neurological disorders in general.
"I think what gene therapy provides us is a new opportunity to really target the specific problem of the disease at its core,” Lonser told NeurologyLive.
