Gene Therapy Trial Makes Headway in Canavan Disease


Data from the first 3 of the 8 patients dosed indicates that the patients improved on the GMFM and the MSEL.

A phase 1/2 clinical trial (NCT04833907) of Myrtelle’s rAAV-Olig001-ASPA (MYR-101), an investigational recombinant adeno-associated virus (rAAV) vector-based gene therapy intended to treat Canavan disease (CD), has completed dosing of the first 8 patients.1

rAAV-Olig001-ASPA is directed at oligodendrocytes and intended to restore function of ASPA, the disease targeted enzyme. Six-month data from the first 3 of the 8 patients dosed indicates that the patients improved on the Gross Motor Function Measure (GMFM) and the Mullen Scales of Early Learning (MSEL) and showed brain white matter and myelin content increases. Safety data were favorable, and no treatment-related adverse events (AEs) were reported.

“Encouraged by the efficacy and safety results to date, we plan to meet with regulatory authorities to discuss advancing this therapy into the final phase of clinical development with the ultimate goal of seeking approval,” Armen Asatryan, MD, MPH, chief medical officer, Myrtelle, said in a statement.1 “Given the progressive nature of Canavan disease and the data from the ongoing trial, we are driven to continue our work to bring this potentially important therapy to the patients who currently do not have treatment options.”

The open-label clinical trial will enroll approximately 24 patients between the ages of 3 months and 60 months (inclusive) who have been diagnosed with typical CD. Patients who have a life expectancy less than 12 months for any reason, a GMFM-88 total raw score greater than 35%, clinically significant out-of-range lab values, a history of severe allergic reaction or anaphylaxis, or absolute contraindications to immunosuppression or MRI will be excluded from participation in the study. Additional exclusion criteria relate to patient health status and treatment history.

The participants will be divided into 3 cohorts based on age, with cohort 1 including patients older than 36 months, cohort 2 including patients aged 15 months to 36 months, and cohort 3 including patients younger than 15 months. Patients will receive 3.7x1013 vg of rAAV-Olig001-ASPA as a single intracerebroventricular administration delivered via neurosurgery. The participants will also receive post-operative regimens of levetiracetam and prednisone for the purposes of preventing seizure activity and immunological responses, respectively. The primary end point is the number, severity, and causal relationship of AEs. Secondary end points include the change from baseline in myelination, N-Acetyl-Aspartate (NAA) concentrations in the brain and cerebrospinal fluid, a seizure assessment, and scores on the GMFM-88, MSEL, and the Canavan Neurological Evaluation. The study is taking place at Dayton Children’s Hospital in Ohio and has an estimated completion date of March 31, 2024.

rAAV-Olig001-ASPA was granted Advanced Therapy Medicinal Product (ATMP) classification by the European Medicines Agency (EMA) in September 2022, and was also previously granted orphan drug, rare pediatric disease, and fast track designations by the FDA.2 Additional safety and efficacy data will be presented by Asatryan at the October 2022 Meeting on the Mesa conference held by the Association for Regenerative Medicine in Carlsbad, CA.

1. Myrtelle completes dosing of 8 patients with canavan disease in its phase 1/2 clinical trial of the investigational gene therapy rAAV-Olig001-ASPA. News release. Myrtelle Inc. September 20, 2022. 
2. Myrtelle’s rAAV-Olig001-ASPA gene therapy candidate for canavan disease receives advanced therapy medicinal product classification from the european medicines agency. News release. Myrtelle Inc. September 7, 2022. 
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