Taysha Snags FDA Breakthrough Therapy Designation for Rett Syndrome Gene Therapy TSHA-102

Taysha Gene Therapies’ TSHA-102, an investigational adeno-associated virus (AAV) vector-based gene therapy intended to treat Rett syndrome, has been granted breakthrough therapy designation by the FDA.¹

The therapy is currently being evaluated in the phase 1/2 REVEAL adolescent and adult clinical trial (NCT05606614) and the separate phase 1/2 REVEAL Pediatric Study clinical trial (NCT06152237). Alongside the news of the designation, Taysha announced that based on results from part A of the REVEAL trials, the FDA has aligned with the company on the pivotal trial protocol and statistical analysis plan (SAP) that Taysha plans to use in support of a biologics license application (BLA) submission for TSHA-102. The alignment came after outstanding clinical and statistical queries were resolved.

As of a May 2025 data cut off, patients treated with TSHA-102 in Part A of REVEAL achieved a 100%response rate with regard to gain or regain of 1 or more defined developmental milestones, which constitutes the pivotal trial primary end point. Taysha noted that based on natural history data, there is a less than 6.7% likelihood of such developmental milestones being gained or regained without treatment. Taysha characterized the safety profile of the gene therapy product as “well-tolerated” in Part A.

“Breakthrough therapy designation highlights the FDA’s recognition of both the significant unmet medical need across the estimated 10,000 patients suffering from Rett syndrome in the United States and the potential of TSHA-102 to redefine the treatment paradigm for this devastating disease,” Rumana Haque-Ahmed, the chief regulatory officer of Taysha, said in a statement.¹ “This designation was granted following the FDA’s review of available clinical data from the 12 patients treated in Part A of our REVEAL trials, which support the potential of TSHA-102 to improve function and enable achievement of developmental milestones across core areas of disease that may significantly impact patient and caregiver lives. The disease burden in Rett syndrome continues to be significant, and we are encouraged by the potential of TSHA-102 to address its underlying cause. We look forward to continued collaboration with the FDA as we advance toward potential registration.”

Taysha highlighted 2 areas of alignment regarding the REVEAL pivotal study protocol and SAP that have been finalized with the FDA. The first of these is using a 6-month interim analysis, based on rigorous evaluation criteria, as the basis of a BLA submission. The second is the minimum criteria for rejecting the null hypothesis: The null hypothesis, that 1 in 15 patients (6.7%) aged 6 years or older may, without treatment, gain or regain 1 of 28 developmental milestones defined by natural history may be rejected if a response rate of at least 5 out of 15 patients (33%) is observed.

“We are pleased to have finalized alignment with the FDA on our pivotal trial protocol and SAP, including the 6-month interim analysis that has potential to expedite our BLA submission for TSHA-102 by at least 2 full quarters,” Sukumar Nagendran, MD, the president and head of R&D of Taysha, added to the statement.¹ “Importantly, the inclusion of an interim analysis was enabled by the rigorous criteria we developed in Part A to evaluate the therapeutic impact of TSHA-102 and the unprecedented early responses observed across patients that continue to deepen over time. This regulatory progress reinforces our BLA readiness and allows us to focus on execution. Weremain on track to initiate patient enrollment for our REVEAL pivotal trial in the fourth quarter of 2025.”

CGTLive® previously spoke to Nagendran in late 2023 about unmet needs in Rett syndrome and the design of TSHA-102. He gave an in-depth description of how TSHA-102 functions and an overview of the design of the REVEAL clinical trial.

“TSHA-102 is a gene therapy given intrathecally into the lumbar area between L4 and L5,” Nagendran told CGTLive. “It's a simple procedure done by lumbar puncture. That allows it to be done in multiple sites in many parts of the country, even in an outpatient setting, inpatient setting, or in a hospital, etc. Ease of use is paramount here...”

REFERENCE
1. Taysha Gene Therapies announces FDA breakthrough therapy designation and provides positive regulatory update on TSHA-102 in Rett Syndrome. News release. Taysha Gene Therapies, Inc. October 2, 2025. Accessed October 3, 2025. https://ir.tayshagtx.com/news-releases/news-release-details/taysha-gene-therapies-announces-fda-breakthrough-therapy