Taysha Gene Therapies Receives Breakthrough Therapy Designation and Reports Regulatory Progress on TSHA-102 in Rett Syndrome
Friday, October 03, 2025
Taysha Gene Therapies has announced that the US Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to TSHA-102, its investigational gene therapy for Rett syndrome.
TSHA-102 has received multiple regulatory designations, including Breakthrough Therapy, Regenerative Medicine Advanced Therapy, Fast Track, Orphan Drug and Rare Paediatric Disease designations from the FDA, Orphan Drug designation from the European Commission and Innovative Licensing and Access Pathway designation from the UK regulator.
Rett syndrome is a rare genetic neurodevelopmental disorder caused by mutations in the MECP2 gene. It is marked by loss of communication skills, impaired hand function, developmental regression, motor and respiratory difficulties, seizures, and intellectual disability. The condition primarily affects females and has no approved disease-modifying therapies. It is estimated to affect between 15,000 and 20,000 patients across the US, EU and UK.
The company has also confirmed final alignment with the FDA on the pivotal REVEAL trial protocol and statistical analysis plan, which are expected to support a future Biologics License Application (BLA).
The designation and regulatory progress were based on clinical results from Part A of the ongoing REVEAL Phase 1/2 adolescent/adult and paediatric trials. TSHA-102, an intrathecally delivered AAV9 gene therapy, is designed as a one-time treatment targeting the underlying genetic cause of Rett syndrome through delivery of a functional form of MECP2 to cells in the central nervous system.
Clinical data demonstrated a favourable safety profile and a 100% response rate at the May 2025 cut-off, with patients gaining or regaining at least one developmental milestone. These results were supported by dose-related improvements across additional measures, including motor behaviour and clinician-assessed global improvement.
The pivotal REVEAL trial will evaluate a single high dose of TSHA-102 in 15 females aged 6 to under 22 years with Rett syndrome in the developmental plateau stage. Each patient will act as their own control. The primary endpoint will be the proportion of patients who achieve one or more defined developmental milestones across communication, fine motor and gross motor domains. These milestones have been shown to have a very low likelihood of occurring without treatment in this population. Assessments will be standardised and reviewed independently by blinded raters using video evidence.
An interim analysis at six months is included in the trial design and may provide the basis for a BLA submission. This approach is supported by previous trial findings, where 83% of patients receiving high-dose treatment achieved milestone gains within six months.
Source: tayshagtx.com
