Taysha Gene Therapies Drops Development of Giant Axonal Neuropathy Gene Therapy TSHA-120


The company is now prioritizing its gene therapy program for Rett syndrome.

Taysha Gene Therapies has discontinued development of its lead candidate TSHA-120, an investigational adeno-associated virus (AAV) vector-based gene therapy that was being evaluated for the treatment of giant axonal neuropathy (GAN).1

Taysha noted that the decision was made after the company obtained feedback from a Type C meeting with the FDA that was related to the roadmap to approval for the gene therapy. Furthermore, Taysha also announced that Astellas Gene Therapies, with which Taysha has an Option Agreement, has made the choice not to claim an exclusive license for TSHA-120.

The gene therapy was being evaluated in an open-label phase 1/2 clinical trial (NCT02362438). In a June 2023 update, Taysha reported that participants treated with TSHA-120 had a 99% probability of positive treatment effect on slowing disease progression, with an estimated average treatment effect of 31% on the Modified Friedreich’s Ataxia Rating Scale and an estimated treatment effect of 28% on Motor Function Measure 32 (MFM32) Domain 3 (distal motor function – hands) compared to natural history data.2 Participants also had a 100% probability of positive treatment effect on slowing disease progression in visual acuity, as measured by Logarithm of the Minimum Angle of Resolution, with an estimated treatment effect of 70% in the right eye and 51% in the left eye. 

“We believe we have made significant progress in demonstrating the therapeutic potential of TSHA-120 and identifying a potential registrational path,” Sean P. Nolan, the chairman and chief executive officer of Taysha, said in a statement.1 “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 biologics license application (BLA) submission in this ultra-rare neurodegenerative disease. I want to express our gratitude to the patients and families who participated in the trial, the GAN community, and the National Institutes of Health for their partnership in establishing the foundation for a potential treatment option in GAN. 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.”

Taysha stated that in the feedback, the FDA had suggested that in order to best demonstrate efficacy of the gene therapy, a randomized, double-blind, placebo-controlled study was recommended; Taysha has now expressed concerns about the feasibility of such an approach.1 This suggestion from the FDA was a continuation of its previous stance, which had been expressed in a Type B end-of-Phase 2 meeting between the company and the FDA held in early 2023.1,3 At the time, the agency also pointed out that the trial design would need to take into account the heterogeneity of progression in GAN. In addition to the recommendations, the FDA noted at the time that the MFM32 score would be an acceptable end point for a double-blind, placebo-controlled study and stated that pending a review of a Chemistry, Manufacturing, and Controls data package, the manufacturing approach for the gene therapy product was appropriate for pivotal-stage and commercial production. Following that meeting, Taysha submitted follow-up questions regarding the design and necessary evidence for a BLA submission. In the Type C meeting feedback, the FDA noted a potential alternative route to approval could include a single-arm study that incorporates longer-term follow-up and matching of participants to an external control group.

Taysha is now prioritizing the development of its clinical stage AAV vector-based gene therapy for the treatment of Rett syndrome, TSHA-201.1 TSHA-201 recently received fast track designation from the FDA and demonstrated improvements in measurements including the Clinical Global Impressions–Improvement scale adapted to Rett syndrome in the first patient dosed in the phase 1/2 REVEAL clinical trial (NCT05606614).4,5

“This strategic program prioritization is expected to extend our cash runway into the fourth quarter of 2025 to support the continued clinical development of TSHA-102 in Rett syndrome, a rare neurodevelopmental disorder with no approved treatments that target the genetic root cause of the disease,” Nolan continued.1 “We remain focused on continuing to evaluate the therapeutic potential of TSHA-102 in our ongoing REVEAL phase 1/2 trial in adults and our planned pediatric trial.”

1. Taysha Gene Therapies provides update on TSHA-120 program in giant axonal neuropathy (GAN). News release. Taysha Gene Therapies, Inc. September 19, 2023. Accessed September 21, 2023. https://ir.tayshagtx.com/news-releases/news-release-details/taysha-gene-therapies-provides-update-tsha-120-program-giant-0
2. Taysha Gene Therapies Provides Clinical Updates for Investigational Programs TSHA-120 in Giant Axonal Neuropathy (GAN) and TSHA-102 in Rett Syndrome at R&D Day. News release. Taysha Gene Therapies. June 28, 2023. Accessed September 21, 2023. https://www.biospace.com/article/releases/taysha-gene-therapies-provides-clinical-updates-for-investigational-programs-tsha-120-in-giant-axonal-neuropathy-gan-and-tsha-102-in-rett-syndrome-at-r-and-d-day/
3. Taysha Gene Therapies provides update on TSHA-120 program in giant axonal neuropathy and a 2023 corporate outlook. News release. Taysha Gene Therapies, Inc. January 31, 2023. Accessed September 21, 2023. https://ir.tayshagtx.com/news-releases/news-release-details/taysha-gene-therapies-provides-update-tsha-120-program-giant
4. Taysha Gene Therapies Announces Fast Track Designation Granted by U.S. FDA for TSHA-102 in Rett Syndrome. News Release. Taysha Gene Therapies. Published August 24, 2023. Accessed September 21, 2023. https://ir.tayshagtx.com/news-releases/news-release-details/taysha-gene-therapies-announces-fast-track-designation-granted
5. Taysha Gene Therapies reports initial clinical data from first adult Rett syndrome patient dosed in reveal phase 1/2 trial and provides corporate update with second quarter 2023 financial results. News release. Taysha Gene Therapies, Inc. August 14, 2023. Accessed September 21, 2023. https://ir.tayshagtx.com/news-releases/news-release-details/taysha-gene-therapies-reports-initial-clinical-data-first-adult
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