Investigational Gene Therapy for Parkinson Disease Gets Fast Track Status

The Food and Drug Administration (FDA) has granted Fast Track designation to AB-1005 for the treatment of moderate Parkinson disease. 

AB-1005 is an investigational gene therapy based on adeno-associated viral vector serotype 2 containing the human glial cell line-derived neurotrophic factor (GDNF) transgene.

Following direct neurosurgical injection with magnetic resonance imaging (MRI)-monitored convection enhanced delivery, AB-1005 is designed to allow for stable and continuous expression of GDNF in localized regions of the brain. 

The designation is supported by data from an 18-month phase 1b trial (ClinicalTrials.gov Identifier: NCT04167540) that evaluated the safety and potential clinical effect of a one-time bilateral delivery of AB-1005 directly to the putamen in 11 patients with Parkinson disease. The study included 2 cohorts: mild stage (n=6) and moderate stage (n=5).

As of November 3, 2023, findings showed most adverse events (AEs) reported were transient and were perioperative events (less than 1 month from treatment); the AEs included headache, tremor, dyskinesia, arthralgia, musculoskeletal chest pain, fatigue, COVID-19, and magnetic resonance imaging MRI abnormalities. There were 57 nonserious AEs and 6 serious AEs reported. 

In the mild cohort, there was relative stability from baseline to 18 months based on assessments using both the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part II patient-reported activities of daily living scores and Part III clinician-rated motor examination scores in “on” and “off” medication states. Results 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 using patient-reported PD motor diaries. One patient declined to complete the diary and 1 patient had a genetic defect with unknown pathological significance. According to the AskBio, these factors likely contributed to worsening outcomes in the group.

In the moderate cohort, improvements in MDS-UPDRS scores for Part II activities of daily living (-3.8 points from baseline), and Part III motor examination (-20.4 points “off” medication and -10.6 points “on” medication compared with baseline) were observed at 18 months. Using motor diaries, patients reported a 2.2 hour improvement in “Good on” time, a 0.5 hour reduction in “on” time with troublesome dyskinesia; and a 1.7 hour reduction in “off” time. Additionally, a reduction in dopaminergic medication use post treatment was noted.

The Company is currently enrolling patients in the randomized, double-blind, surgery-controlled phase 2 REGENERATE-PD trial (ClinicalTrials.gov Identifier: NCT06285643). The trial will evaluate the efficacy and safety of AB-1005 in adults 45 to 75 years of age with moderate stage Parkinson disease. 

“These designations clearly underscore the importance of developing innovative therapies for those living with Parkinson’s disease, where a significant unmet need still exists,” said Krystof Bankiewicz, MD, PhD, Scientific Chair, Parkinson’s and MSA, AskBio. “They further highlight the willingness of key regulatory bodies to support the accelerated development of AB-1005 with a focus on the potential benefit to patients.”

This article originally appeared on MPR