Myrtelle’s Canavan Disease Gene Therapy Selected for FDA START Pilot Program


The therapy, rAAV-Olig001-ASPA, has shown positive clinical benefits in several interim updates from an ongoing, first-in-human phase 1/2 clinical trial (NCT04833907).

Nancy Barone Kribbs, PhD, the senior vice president of Global Regulatory Affairs at Myrtelle

Nancy Barone Kribbs, PhD

(Image credit: Myrtelle)

Myrtelle Inc has announced that the FDA selected its investigational gene therapy, rAAV-Olig001-ASPA (previously known as MYR-101), for inclusion in its Support for Clinical Trials Advancing Rare Disease Therapeutics (START) Pilot Program.1 The viral vector-delivered therapy is in development for the treatment of Canavan disease (CD), a rare and fatal childhood genetic brain disease that occurs as a result of mutations in the ASPA gene.

The START program is intended to facilitate efficient communication between sponsor and agency staff to aid in completion of regulatory milestones and to speed up the development of promising therapies. Myrtelle’s rAAV-Olig001-ASPA was one of a few eligible CBER-regulated products, as it has shown “clinical benefit for rare diseases with unmet medical needs” and the company has shown “ability to accelerate development to market application,” according to the release.1 The communication between the 2 entities will go beyond the standard available formal meetings—occurring on an ad hoc basis—with an aim of reducing wait times associated with the formal FDA meeting process.

Nancy Barone Kribbs, PhD, the senior vice president of Global Regulatory Affairs at Myrtelle, said in a statement1 that acceptance into the program is “an honor” because of its recognition of rAAV-Olig001-ASPA as a potential treatment. “Opening the lines of communications beyond traditional meeting pathways provides the opportunity to quickly address development issues that would otherwise delay progression to market application. We are encouraged by the opportunity to facilitate the development of a potential treatment for Canavan children who are without treatment options,” she said.

Currently, the company is conducting a first-in-human, phase 1/2 trial (NCT04833907) assessing rAAV-Olig001-ASPA in patients with Canavan disease.2 The estimated enrollment is 24 patients, in which they are intracerebroventricularly administered a single, 3.7 × 1013 vg dose of treatment, along with daily doses of 20 to 50 mg/kg of levetiracetam (Keppra; UCB Pharma) in the postoperative period plus 3 months per standard of care for seizure prevention. Additionally, patients will receive a prednisone tapered dose for a 3-month postoperative period to prevent or reduce delayed immunological responses.

Key Takeaways

  • Myrtelle's gene therapy rAAV-Olig001-ASPA has been selected for the FDA's START pilot program to advance rare disease therapeutics.
  • rAAV-Olig001-ASPA is being assessed in a first-in-human phase 1/2 trial for Canavan disease; thus far it has shown promising early data in improving brain volume and function.
  • FDA has already granted RMAT, Orphan Drug, Rare Pediatric Disease, and Fast Track designations to the therapy.

In April 2024, rAAV-Olig001-ASPA received a Regenerative Medicine Advanced Therapy (RMAT) designation from the FDA.3 Previously it has also been issued Orphan Drug, Rare Pediatric Disease, and Fast Track designations from the FDA, as well as Orphan Drug Designation and Advanced Therapy Medicinal Product classification from the European Medicines Agency, and Innovative Licensing and Access Pathway from the United Kingdom Medicines & Healthcare Products Regulatory Agency.

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The aforementioned clinical benefit of the gene therapy was on display in a pair of 2023 updates from the ongoing phase 1/2 trial; the first of which included positive data for 8 patients who had been followed through 3 months of follow-up assessment.4 According to that announcement, there were reported increases in white matter, grey matter, and total brain volumes, as well as a reduction in the volume of cerebrospinal fluid (CSF) in most patients by MRI through the 3-month time point. Additional measurements of cognitive and motor function—assessed via the Mullen Scales of Early Learning (MSEL) and Gross Motor Function Measure (GMFM) scales, respectively—suggested multidomain improvements for the study cohort. In comparison, untreated patients experience continuous clinical decline in these areas.4

The first 3 patients treated with rAAV-Olig001-ASPA in the first cohort were, at the time, a minimum of 18 months post therapy administration. Assessments of those patients at later time points also showed improvements on imaging and validated functional scale measurements, according to Myrtelle. Notably, no serious drug-related adverse events have been observed to date.

In October 2023, the company presented 12-month data at the Alliance for Regenerative Medicine, the Cell & Gene Meeting on the Mesa, shortly after announcing it had completed dosing in the eighth patient in the trial.5,6 Those data were presented by Mark Hurtt, MD, the at-the-time acting chief medical officer of Myrtelle, and showed significant improvements from baseline in mean white matter volume (P = .0071) and mean myelin volume (P = .0102).6 Additionally, they showed significant changes in the MSEL 5-domain mean (P = .0076), outpacing the natural history by a significant margin (P = .0346), as well as improving MSEL gross motor developmental age (P = .0038), MSEL receptive language developmental age (P = .0058), and expressive language developmental age (P = .0081).

“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 at the time.5

1. Myrtelle Announces that the FDA has Selected rAAV-Olig001-ASPA Gene Therapy Candidate for the Treatment of Canavan Disease for the Support for Clinical Trials Advancing Rare Disease Therapeutics (START) Pilot Program. News release. Myrtelle Inc. June 5, 2024. Accessed July 2, 2024.
2. rAAV-Olig001-ASPA Gene Therapy for Treatment of Children With Typical Canavan Disease (CAN-GT). Updated April 11, 2024. Accessed July 2, 2024.
3. Myrtelle's rAAV-Olig001-ASPA Gene Therapy Candidate for Canavan Disease Receives Regenerative Medicine Advanced Therapy (RMAT) Designation from the U.S. Food and Drug Administration. News release. Myrtelle Inc. April 2, 2024. Accessed July 2, 2024.
4. Myrtelle Announces Positive Interim Data in Phase 1/2 Clinical Trial of Its Proprietary Investigational Gene Therapy rAAV-Olig001-ASPA in Canavan Disease. News release. Myrtelle Inc. January 9, 2023. Accessed July 2, 2024.
5. 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. Myrtelle Inc. October 9. 2023. Accessed July 2, 2024.
6. Hurtt M. MYR-101 Gene Therapy for Canavan Disease Preliminary One-Year Results. Presented at: Meeting on The Mesa; October 11, 2023; Carlsbad, CA.
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