MeiraGTx’s Parkinson Disease Gene Therapy AAV-GAD Improves Motor Scores and Patient-Reported Quality of Life in Sham-Controlled Study
For the patients treated at the high dose, an average improvement of 18 points from baseline was observed in UPDRS Part 3 “off” medication score at 26 weeks posttreatment.
MeiraGTx’s AAV-GAD, an investigational adeno-associated virus (AAV) vector-based gene therapy, has improved MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part 3 and Parkinson’s Disease Questionnaire (PDQ-39) scores compared to baseline in some patients with idiopathic Parkinson disease (PD) treated in the phase 1/2 MGT-GAD-025 clinical trial (NCT05603312).1
MGT-GAD-025 treated 5 patients with a low dose of AAV-GAD (7.0×1010 vg), 5 patients with a high dose of AAV-GAD (21×1010 vg), and 4 patients with a sham procedure. For the patients treated at the high dose, an average improvement of 18 points from baseline was observed in UPDRS Part 3 “off” medication score at 26 weeks posttreatment (P = .03). On the other hand, there was no significant change in this score recorded in the same timeframe for the patients treated with the low dose and the patients treated with the sham procedure.
Furthermore, at 26 weeks posttreatment, an 8 point improvement from baseline on PDQ-39 score was recorded for patients treated at the high dose (P = .02), a 6 point improvement from baseline was recorded for patients treated at the low dose (P = .04), and a statistically insignificant worsening of 0.2 points was recorded for the patients treated with the sham procedure. MeiraGTx noted that the dose response for PDQ-39 was 100% for the high dose group, 60% for the low dose group, and 25% in the sham group. In terms of safety, AAV-GAD was characterized as “well-tolerated”. No serious adverse events related to the gene therapy were reported.
“With the completion of this randomized, double-blinded bridging study, we have also demonstrated with even very small numbers of subjects that AAV-GAD treatment results in significant and clinically meaningful changes in key efficacy endpoints in PD,” Alexandria Forbes, PhD, the president and chief executive officer of MeiraGTx, said in a statement.1 “For the UPDRS Part 3 in the ‘off’ state, a change of 5 to 10 points is considered clinically meaningful. The 18-point change observed in the high dose arm in this study underscores the very substantial impact of AAV-GAD treatment in these PD patients. Similarly, for the PDQ-39, where a 2 to 4-point change is considered clinically meaningful, the 8-point and 6-point changes observed in the high and low dose groups, respectively, again indicate a substantial and clinically meaningful impact of AAV-GAD treatment. These data demonstrate the impact of using highly targeted local delivery of gene-based therapy to correct the aberrant circuitry that results from the depletion of dopamine in the brain of idiopathic PD patients as the disease progresses. AAV-GAD treatment is designed to normalize circuit function in all forms of PD with its potential benefit not limited to any single type of PD. The significant, substantial, and clinically meaningful changes observed in this small, sham-controlled study provide us with a clear path forward in our clinical development strategy and underpin our discussions with regulators in the US, Europe, and Japan with the goal of initiating a phase 3 study to support approval of this disease-modifying treatment globally.”
PD is currently a growing area of interest for the application of gene therapy. Recently, CGTLive® spoke with Ignacio Mata, PhD, an associate professor of neurology at the Cleveland Clinic Lerner Institute, to learn more about the challenges of developing gene therapy products in PD and which approaches are most likely to effectively provide benefit to patients.
“I think the ones that are ongoing right now are actually not trying to fix a genetic problem (fix the variant or fix the protein that is damaged by the variant),” Mata told CGTLive. “I think the most successful, at least in animal models, has been treating cells with either BDNF or GDNF, which are neurotrophic factors that might help either the neurons that are already there to stay alive basically and continue the production of dopamine. But I think that's one of the ways to do it”
