Safety and Tolerability Confirmed in MeiraGTx's Gene Therapy Study for Parkinson's

MeiraGTx Holdings plc (NASDAQ:MGTX), a vertically integrated, clinical-stage genetic medicines company, today announced top-line data from its clinical bridging study of AAV-GAD for the treatment of Parkinson's disease, MGT-GAD-025.

MGT-GAD-025 is a 6-month, three-arm, randomized, double-blind, sham-controlled study using AAV-GAD drug product manufactured by MeiraGTx at its wholly-owned facilities with its commercial platform process. Participants had idiopathic Parkinson's disease, a history of levodopa responsiveness for at least 12 months, and a UPDRS Part 3 score of ≥25 points in the "off" state. Fourteen subjects were randomized to one of three groups (high dose n=5, low dose n=5, and sham n=4).

Subjects received either AAV-GAD infused bilaterally into the subthalamic nucleus or a sham procedure in a blinded fashion. The total dose per treated participant was 7.0×1010 vg (low dose group) or 21×1010 vg (high dose group). The primary objective of the study was to evaluate the safety and tolerability of AAV-GAD, with exploratory efficacy endpoints including the mean change from baseline to Week 26 in MDS-UPDRS Part 3 (motor examination) scores in the "off" state and the Parkinson's Disease Questionnaire (PDQ-39) score, a key patient-reported quality of life measure in Parkinson's disease. Subjects who completed this trial may enroll in a long-term follow-up study (NCT05894343), where they will be monitored for a total of five years post-treatment.

Top-line data summary:

• AAV-GAD was safe and well tolerated, with no serious adverse events (SAEs) related to AAV-GAD treatment.
• At Week 26, a statistically significant 18-point average improvement from baseline in UPDRS Part 3 "off" medication score was demonstrated in the high dose group (p=0.03), with no significant change in the sham or low dose groups.
• Significant improvements from baseline in the disease-specific, patient-reported quality of life PDQ-39 score were demonstrated in both the high and low dose groups with no significant change in the sham group at Week 26:
  • In the high dose AAV-GAD group, the PDQ-39 score improved by 8 points from baseline (p=0.02), the low dose group improved by 6 points from baseline (p=0.04), while the 0.2 point worsening in the sham surgery group was not statistically significant.
  • A dose response in PDQ-39 score was observed, with 100% of participants in the high dose group, 60% of participants in the low dose group, and 25% of participants in the sham surgery group reporting an improvement.
  • For the PDQ-39 score, there was a trend to significance between the high dose and sham surgery groups at 6 months (n=4 evaluable per group).

Dr. Ali Rezai, M.D., executive chair of the Rockefeller Neuroscience Institute at West Virginia University (WVU), past president of the Congress of Neurological Surgeons, and principal investigator of the AAV-GAD study, stated, "These safety and outcome results are excellent. The extent of motor score improvements in patients who received the high dose treatment combined with significant quality of life improvement measures are very encouraging for both patients and physicians."

"We are excited about these impressive clinical data in Parkinson's disease," said Alexandria Forbes, Ph.D., president and chief executive officer of MeiraGTx. "With material made using our proprietary production process at commercial scale, we have demonstrated that AAV-GAD is safe at all doses studied, including a higher dose than previously tested. We have now treated a total of 58 patients in this development program in 3 independent multicenter clinical studies and have seen no SAEs related to AAV-GAD treatment."

Dr. Forbes continued, "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 Parkinson's disease. 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 Parkinson's 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 Parkinson's patients as the disease progresses. AAV-GAD treatment is designed to normalize circuit function in all forms of Parkinson's disease with its potential benefit not limited to any single type of Parkinson's. 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."