Canavan Gene Therapy Improves Developmental Measures Compared to Natural History


MSEL 5-mean domain, receptive language, and expressive language scores were significantly improved from baseline in treated participants.

Myrtelle Therapeutics has announced positive 1-year data from a phase 1/2 trial (NCT04833907) of MYR-101 adeno-associated virus (AAV) vector gene therapy including improvements in neurological biomarkers and developmental outcomes in patients with Canavan disease (CD).1

The updated, 12-month data were presented at the Cell & Gene Meeting on the Mesa 2023, held October 10-12 in Carlsbad, California, by Myrtelle’s acting chief medical officer, Mark Hurtt, MD.

“CD is a lethal brain disorder. It’s an autosomal dominant defect in ASPA...there’s about 1,000 patients in the US and 5,000 patients worldwide who are affected. These children do not develop cognitive or motor treatment is available, and they have early deaths,” Hurtt said during his presentation.1 “Our strategy is simple... We want to correct the underlying gene defect, restore function in oligodendrocytes... and improve the kids’ function.”

The study has enrolled 8 patients with CD aged 11 to 59 months at the time of treatment. The participants had increases in mean white matter volume from baseline at months 6 (P = .0060) and 12 (P = .0002) as well as in myelin volume at months 6 (P = .0992) and 12 (P = .0190).1

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\Developmentally, participants had increases on Mullen Scales of Early Learning (MSEL) 5-domain mean at months 6 (P = .0276) and 12 (P = .0004) and specifically on gross motor domain at months 6 (P = .1484) and 12 (P = .0516), receptive language at months 6 (P = .0083) and 12 (P = .0650), and expressive language at months 6 (P = .0127) and 12 (P = .0514). At month 12, MSEL 5-domain mean scores were significantly improved from natural history (P = .0260). MSEL gross motor scores showed a similar trend compared with natural history (P = .1501).1

MYR-101 has been well-tolerated so far, with no serious adverse events (AEs) deemed possibly or probably related to the therapy. Two non-serious AEs related to the therapy were a moderate fever lasting 2 days and a mild rash that resolved the same day. Seven patients (87.5%) experienced at least 1 AE, the most common of which were seizures (n = 5; 62.5%) and infections (n = 4, 50%).

Clinical Takeaways

  • Positive 1-year data from a phase 1/2 trial of MYR-101 gene therapy in Canavan disease patients were presented at the Cell & Gene Meeting on the Mesa 2023.
  • Patients in the study experienced notable increases in white matter and myelin volume, along with significant developmental improvements in gross motor skills and language development, demonstrating the therapy's potential efficacy.
  • The MYR-101 gene therapy has shown good tolerability with minimal serious adverse events.

Hurtt also shared video footage of a treated participant from the study at baseline and 3-, 6-, and 12-month timepoints posttreatment. Before treatment, the child did not have head control and was floppy. At month 3, he has excellent head control and is learning to control his trunk. At month 6, he is able to extend and stand with help from stability support at the hip. At 12 months, he is sitting unassisted, has demonstrable fine motor skills, and is able to use a walker with physical therapy.

“Results obtained to date are encouraging and continue to reinforce the hypothesis that addressing the ASPA genetic deficit specifically in oligodendrocytes in patients with Canavan disease can potentially restore oligodendrocyte health and myelination and support functional improvements,” Hurtt said in a statement.2 “We look forward to sharing details at the upcoming presentation and to discussing further development with global regulatory authorities in support of potential approvals.”

1. Hurtt M. MYR-101 gene therapy for Canavan disease: Preliminary one-year results. Presented at: Cell & Gene Meeting on the Mesa 2023, October 10-12, in Carlsbad, California.
2. Myrtelle announces presentation of positive 12-month post treatment data in its first-in-human clinical study of rAAV-Olig001-ASPA gene therapy at the 2023 Cell & Gene Meeting on the Mesa held by the Alliance for Regenerative Medicine. News release. October 10, 2023.
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