Eladocagene exuparvovec 280 giga vector genomes/0.5ml solution for infusion vials

IntroductionAromatic L-amino acid decarboxylase (AADC) deficiency is a rare disease with symptoms including movement disorders, developmental delays, and autonomic symptoms starting from birth; further, patients with AADC deficiency are at a high risk of death in the first decade of life. Limited information on the impact of treatment with gene therapy on patients' disease trajectories and survival, quality-of-life, and resource usage benefits are available.MethodA cohort-based model with a lifetime horizon has been developed, based on motor milestones, to estimate the long-term benefits for patients after treatment with eladocagene exuparvovec compared to best supportive care (BSC). The model takes a National Health Service (NHS) perspective using a UK setting. The model comprises two parts: the developmental phase, in which patients with initially no motor function can progress to other motor milestone states, and a long-term projection phase. Efficacy for eladocagene exuparvovec is derived from clinical trial data with a duration up to 120 months. As the incidence of AADC deficiency is low, data for key model inputs is lacking; therefore estimates of survival by motor milestone were based on proxy diseases. A disease-specific utility study provided quality of life inputs and a burden of illness study informed inputs for disease management.ResultsThe model indicates survival (25.25 undiscounted life years gained) and quality-of-life benefits (20.21 undiscounted quality-adjusted life years [QALYs] gained) for patients treated with eladocagene exuparvovec compared to BSC. Resource usage costs are greater for patients treated with eladocagene exuparvovec, mainly due to the increased life expectancy during which patients accrue additional healthcare resource usage. Scenario analyses indicate robust results.ConclusionThis study assessed long-term outcomes for patients with AADC deficiency. Patients treated with eladocagene exuparvovec were found to have improved survival and quality of life benefits compared to patients treated with BSC.

Abstract licence: CC BY-NC 4.0

Abstract Purpose We present two clinical cases of frameless, neuronavigated gene therapy with eladocagene exuparvovec for aromatic L-amino acid decarboxylase (AADC) deficiency in pediatric patients, detailing the targeted bilateral microdose delivery of viral vectors into the putamen and highlighting the feasibility and challenges of this approach in managing a rare neurometabolic disorder. Methods Two patients with a confirmed diagnosis of AADCD underwent frameless stereotactic gene therapy. High-resolution 3 T MRI-guided trajectories were planned for the targeted bilateral putaminal infusion of 0.32 ml of eladocagene exuparvovec (AAV2-hAADC). The agent was delivered via a SmartFlow Neuro Ventricular Cannula in a “Z-pattern,” retracting the cannula 2 mm every 9 min to achieve controlled microdosing. Results Accurate frameless drug delivery was achieved in a shorter time than frame-based approaches, with no intraoperative or postoperative complications. One patient showed a small post-ischemic cyst on the 1-month follow-up MRI, without any neurological deficits. Over 2 months, both patients demonstrated reduced oculogyric crises, diminished hyperkinesis, and improved head control, with no significant adverse events. Conclusion Frameless, neuronavigated gene therapy for AADC deficiency proved both feasible and safe, with early clinical improvements observed in motor function and symptom control. This technique offers a promising alternative to frame-based methods and expands treatment options for this rare neurometabolic disorder.

Abstract licence: CC BY 4.0