Taysha Gene Therapies announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to TSHA-102, its intrathecally delivered AAV9 gene therapy aimed at treating Rett syndrome. The designation, which is designed to accelerate the development and review of treatments for serious conditions, was granted based on positive clinical evidence from Part A of the ongoing REVEAL Phase 1/2 trials in both adolescent/adult and pediatric patients.
TSHA-102 showed a well-tolerated safety profile and a 100% response rate in patients achieving at least one developmental milestone, a key endpoint with a very low chance of occurring without treatment, according to natural history data. Improvements were also observed in other measures such as motor behavior and clinician assessments. Rett syndrome affects an estimated 10,000 patients in the U.S. and is characterized by severe developmental impairments, underscoring the urgent need for new therapies.
In addition, Taysha confirmed it has finalized alignment with the FDA on the protocol and statistical analysis plan for its pivotal REVEAL trial, which will support the planned Biologics License Application (BLA) submission. The trial will include a six-month interim analysis that could enable an accelerated BLA filing, based on strong early responses seen in the Phase 1/2 data.
The pivotal trial will evaluate a single high-dose intrathecal administration of TSHA-102 in 15 female patients aged 6 to under 22 years who are in the developmental plateau phase of Rett syndrome. Each patient will serve as their own control, with the primary endpoint assessing the percentage who gain or regain one or more of 28 predefined developmental milestones across communication and motor skills. Milestone achievement will be rigorously assessed through video evidence reviewed by independent, blinded raters.
Taysha’s leadership emphasized that the Breakthrough Therapy designation and FDA alignment mark critical milestones in advancing TSHA-102 toward potential approval, with patient enrollment for the pivotal trial expected to begin in the fourth quarter of 2025.