Taysha Discontinues Development of Gene Therapy for Giant Axonal Neuropathy

Rare Daily Staff

Taysha Gene Therapies said it is discontinuing the development of its TSHA-120 program for the treatment of giant axonal neuropathy following a meeting with the U.S. Food and Drug Administration a path to approval for the experimental AAV-based gene therapy.

Taysha also said that Astellas Gene Therapies has elected not to exercise its option to obtain an exclusive license to TSHA-120 under the Option Agreement between Astellas and Taysha.

“We believe we have made significant progress in demonstrating the therapeutic potential of TSHA-120 and identifying a potential registrational path. Following FDA feedback, we have made the decision to discontinue further development of the program due to challenges related to the feasibility of the study designs to support a potential BLA submission in this ultra-rare neurodegenerative disease,” said Sean Nolan, chairman and CEO of Taysha. “We plan to pursue external strategic options for TSHA-120 that may enable further development of TSHA-120 and help patients with this devastating disease.”

The decision to discontinue development of TSHA-120 is expected to extend Taysha’s cash runway into the fourth quarter of 2025 to support the continued clinical development of TSHA-102 in Rett syndrome, a rare neurodevelopmental disorder.

Giant axonal neuropathy (GAN) is caused by loss-of-function mutations in the gene coding for gigaxonin, which results in dysregulation of intermediate filament turnover, an important structural component of the cell. Children with GAN present before the age of five with symptoms including unsteady gait, frequent falls, and motor weakness. Currently, there are no approved treatments for GAN, which results in death for patients in their late teens or early twenties. TSHA-120 has received Orphan Drug and Rare Pediatric Disease designations from FDA and Orphan Drug designation from the European Commission.

In 2022, Taysha submitted and reviewed with the FDA in an end-of-phase 2 meeting, a subset of available evidence from a phase 1/2 clinical trial investigating TSHA-120 for the treatment of GAN, which was initiated by the NIH. FDA feedback included the need to address the heterogeneity of disease progression in GAN and the effort-dependent nature of MFM32 as a primary endpoint in an unblinded study. To further discuss a potential regulatory path forward for TSHA-120, Taysha submitted a new comprehensive analysis of the totality of data from the natural history and interventional trial comparing functional and biological measurements against a Disease Progression Model as part of a meeting request to the FDA in June 2023.

FDA feedback indicated that the agency continues to recommend a randomized, double-blind, placebo-controlled trial as the optimal path to demonstrate efficacy in TSHA-120. Among other areas of feedback, the FDA also provided a potential path for a single-arm trial with an external control group matched with to-be treated patients by multiple prognostic factors and recommended longer term follow up to account for potential bias.

Photo: Sean Nolan, chairman and CEO of Taysha