Parkinson Gene Therapy AB-1005 Continues to Show Promising Results at 18 Months


Patients experienced improvements in ON/OFF time and motor function, with favorable tolerability, paving the way for a phase 2 trial.

Krystof Bankiewicz, MD, PhD, scientific chair of Parkinson’s and MSA at AskBio

Krystof Bankiewicz, MD, PhD

Newly presented data from a phase 1b study (NCT04167540) assessing AskBio’s investigational gene therapy AB-1005 in patients with Parkinson disease (PD) showed that the therapy met its primary end point of successful putamen coverage and was safe over an 18-month period. Although the study was small scale, with only 11 patients included, both mild (n = 6) and moderate (n = 5) forms of PD experienced improvements in ON and OFF time with AB-1005.1

All told, neurosurgical delivery of AB-1005, an investigational adeno-associated viral vector serotype 2 (AAV2) gene therapy containing the human glial cell line-derived neurotrophic factor (GDNF) transgene, resulted in putamen coverage of 63% (±2%), exceeding the goal of greater than 50% coverage. Presented at the 2024 American Academy of Neurology (AAN) Annual Meeting, held April 13-18, in Denver, Colorado, bilateral infusions of the agent within the putamen (up to 1.8 mL) were well tolerated, with no serious adverse events (AEs) associated with the gene therapy or contrast agent. Of note, the company is planning to publish the 18-month results later this year.

This multi-site, parallel assignment, non-randomized trial primarily looked at safety and potential clinical effect of AB-1005, with other secondary outcomes that assessed motor and non-motor function, as well as brain dopaminergic network integrity through DaTSCAN. In the study, which follows patients for up to 5 years post administration, scheduled 6-month postoperative MRIs revealed findings of asymptomatic unilateral T1 hypointensity adjacent to 3 of the putaminal infusion trajectories.

"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 of Parkinson’s and MSA at AskBio, said in a statement.1 "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 disease."

In terms of safety, as of November 3, 2023, 57 nonserious AEs and 6 serious AEs had been reported, most of which were transient and were expected following the operation. The AEs included headache, tremor, dyskinesia, arthralgia, musculoskeletal chest pain, fatigue, COVID-19, and MRI abnormalities. Six serious AEs, reported in 3 patients (mild: n = 1; moderate: n = 2), were all assessed as unrelated to the study treatment. Between mild and moderate patients, those with milder disease had a lower Levodopa Equivalent Daily Dose (LEDD) at baseline and demonstrated further stability of LEDD over 18 months.

According to AskBio, the mild cohort of patients showed relative stability of PD symptoms, as assessed through the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS)- Part 2, over the 18-month treatment period. Similar effects were seen on Part 3 of the scale, which assesses clinician-rated motor examination scores in ON and OFF medication states.

In the mild cohort, patient-reported PD Motor Diaries showed 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. The company noted that 1 patient in this group decline to complete the diary after dosing, and that troublesome dyskinesia and increased OFF time in this cohort may have been because of a genetic defect of an unknown pathological significance. "These factors are believed to have contributed to worsening of "Good ON” state time and “OFF” state time over 18 months for the Mild Cohort," the company wrote.

For the moderate cohort, investigators observed improvements of –3.8 (SE, 3.5) points on MDS-UPDRS-II and improvements of –20.4 (SE, 4.5) points in MDS-UPDRS-III over the 18-month period. The moderate cohort also had a –10.6 (SE, 3.6) point improvement in ON medication state compared with baseline.

READ MORE: Switching to Subcutaneous Zilucoplan Raises No Safety Concerns in Myasthenia Gravis

Using motor diaries, patients in the moderate group reported a 2.2-hour enhancement in good ON time, which was considered clinically meaningful; a 0.5-hour reduction in ON state with troublesome dyskinesia; and a 1.7-hour reduction in OFF state time. This equated to a 23.6% (±11.8%) increase in good ON state time and a 33.1% (±17.4%) decrease in OFF state time. Additionally, those with moderate PD demonstrated a mean LEDD reduction of 258 (±162) mg from baseline, with motor improvements that were observed in the setting of a reduced levodopa requirement.

Christian Rommel, PhD, head of research and development at Bayer’s Pharmaceuticals Division

Christian Rommel, PhD

"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 at Bayer’s Pharmaceuticals Division, said in a statement. "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."

Building off this study, AskBio has already begun to develop a phase 2 trial, dubbed REGENERATE PD, that is expected to be enrolling patients later this year in the US, EU, and UK. The phase 1 REGENERATE-MSA study (NCT04680065), another pivotal study assessing AB-1005 in patients with multiple system atrophy (MSA)-parkinsonian type, had its first patient dosed in Novemeber 2023. REGENERATE MSA-101, a randomized, double-blind, placebo-controlled study, is expected to include 9 patients aged between 35-75 years with a clinical diagnosis of MSA-P.2

Click here for more coverage of AAN 2024.

1. AskBio presents 18-month phase 1b trial results of AB-1005 gene therapy for patients with Parkinson disease. News release. AskBio. April 16, 2024. Accessed April 17, 2024.
2. AskBio announces first patient randomized in phase 1 trial of AB-1005 (AAV2-GDNF) gene therapy for multiple system atrophy-parkinsonian type (MSA-P). News release. AskBio. November 17, 2023. Accessed April 17, 2024.
Related Videos
Ro'ee Gilron, PhD
Monica Verduzco-Gutierrez, MD
Shahid Nimjee, MD, PhD
Peter J. McAllister, MD, FAAN
Video 6 - "Utilization of Neuroimaging in Alzheimer’s Disease"
Video 5 - "Contribution of Multiple Pathways to the Development of Alzheimer’s Disease"
Michael Levy, MD, PhD
© 2024 MJH Life Sciences

All rights reserved.