WAKEFIELD, Mass.– Myrtelle Inc. (“Myrtelle” or the “Company”), a gene therapy company focused on developing transformative treatments for neurodegenerative diseases, today announced that updated positive data in its open-label Phase 1/2 First-in-Human (FIH) clinical trial for Canavan disease (CD) using the Company’s recombinant adeno-associated virus (rAAV) vector-based investigational gene therapy will be presented at the National Tay-Sachs and Allied Diseases Annual Family Conference, taking place in Reston, Virginia June 1-4, 2023. Olga Flamini, MD, PhD, Medical Director at Myrtelle, will deliver a presentation on Friday, June 2, 2023.
Clinical measurements of motor, language, and cognitive function using validated assessment scales that demonstrate mean absolute and percent improvements across multiple domains will be presented, as well as improvements in anatomic and biomarker measurements observed in magnetic resonance imaging (MRI) and spectroscopy (MRS). In particular, patients show mean improvements across multiple subscales of the Gross Motor Function Measure-88 (GMFM-88) and Mullen Scales of Early Learning (MSEL), including first-time achievement of milestones such as sitting, standing with support, and taking steps with assistance, improvement in language ability (verbal and receptive language domains) and improvement in cognitive ability (visual reception domain). Supporting the functional gains, the patient group also shows mean improvements in MRI-based measures of myelin, white matter, grey matter and CSF volumes, along with reductions in NAA levels. Several changes represent statistically significant improvements from baseline over six months post treatment. These improvements in treated patients contrast the deterioration in untreated age-matched CD patients in Myrtelle’s natural history data set. No serious drug-related adverse events have been observed to date.
Myrtelle’s FIH trial utilizes the Company’s proprietary rAAV vector to directly target oligodendrocytes, the brain cells affected in CD that are responsible for producing myelin – the insulating material that enables proper neuronal function. In CD, normal brain development is impaired due to a mutation in the ASPA gene that encodes the enzyme aspartoacylase. The deficiency of aspartoacylase enzyme results in multiple biochemical and anatomic changes, including the inability to metabolize the neurochemical N-acetylaspartate (NAA). The lack of normal aspartoacylase expression negatively impacts brain bioenergetics and development, including myelin production. The oligodendrocyte-targeting rAAV vector-based gene therapy is intended to restore ASPA function and hence the metabolism of NAA and brain development in patients with CD. Under the clinical protocol, patients were treated with a single dose of 3.7 x 1013 vector copies, administered by intraventricular delivery to directly target oligodendrocytes of the brain, where ASPA activity needs to be restored. This direct delivery potentially mitigates certain side effects associated with IV administration such as immune responses, complement activation, increases in liver enzymes, or other off-target complications, thereby avoiding the need of high dose steroid administration. Based on the positive results to date, Myrtelle anticipates meeting with regulatory authorities in the near-term to discuss remaining requirements for product approval. Accordingly, the current study is closed to enrollment, as posted on https://clinicaltrials.gov/ under the identifier NCT04833907.
“We look forward to sharing encouraging updates with the NTSAD community from Myrtelle’s Phase 1/2 gene therapy study using its oligodendrocyte-targeting AAV vector,” said Dr. Flamini. “Connecting with patients and caregivers allows us to incorporate the patient voice into our drug development activities.”
