Pivotal Trial for Taysha's Rett Syndrome Gene Therapy TSHA-102 Doses First Patient

This article was originally published on our sister site, NeurologyLive®.

Taysha Gene Therapies has dosed the first patient in the pivotal phase 3 portion (Part B) of the REVEAL clinical trial (NCT05606614), which is assessing the investigational adeno-associated virus (AAV) vector–based gene therapy TSHA-102 for the treatment of Rett syndrome.¹

The company reported that the initial dosing occurred in the fourth quarter of 2025. Enrollment in the study is ongoing, with plans to enroll a total of 15 female patients between the ages of 6 and less than 22 years. The multicenter trial is evaluating a single intrathecal administration of TSHA-102 at a dose of 1×10¹⁵ total vector genomes (vg).

In conjunction with the dosing announcement, Taysha disclosed that it has received written alignment from the FDA on elements of a potential biologics license application (BLA) strategy for TSHA-102. This alignment pertains to a separate planned clinical trial, ASPIRE (NCT identifier pending), which will evaluate the gene therapy in 3 girls aged 2 to less than 4 years. Patients in ASPIRE will receive a single dose of 1×10¹⁵ total vg, adjusted for lower brain volume in this younger population, with safety as the primary focus. Taysha has aligned with the FDA on the use of at least 3 months of data from ASPIRE to support a BLA submission for an indication that would include patients aged 2 years and older.

"Dosing the first patient in our REVEAL pivotal trial last quarter represents a significant milestone in the development of TSHA-102 for Rett syndrome, and enrollment is further advancing across multiple sites,” Sean P. Nolan, BS, the chairman and chief executive officer of Taysha, said in a statement.¹ “As we progress pivotal development, we continue to maintain consistent and productive dialogue with the FDA. Importantly, we recently reached written alignment with the FDA that our planned BLA submission will include at least 3 months of safety data from 3 patients aged 2 to under 4 years in the ASPIRE trial to support a broad label for patients aged 2 years and older with Rett syndrome. We believe this recent alignment on ASPIRE, together with the alignment on a 6-month interim analysis for our REVEAL pivotal trial, streamlines our path toward BLA submission for TSHA-102. We expect to complete dosing across our REVEAL and ASPIRE trials in the second quarter of 2026. With an estimated 15,000 to 20,000 patients affected by Rett syndrome across the United States, European Union, and United Kingdom and compelling REVEAL Part A clinical data, we see a significant opportunity to redefine the treatment paradigm for this devastating disease with high unmet need.”

Part A of the REVEAL program—which includes adolescent and adult (NCT05606614) and pediatric (NCT06152237) phase 1/2 studies of TSHA-102—remains ongoing. The pediatric study has an estimated primary completion date of November 2, 2028, and Taysha indicated that additional data from Part A are expected to be reported before the end of the first half of 2026.

Notably, previously announced data from Part A of the adolescent and adult study with a data cut off in May 2025 showed that patients treated with TSHA-102 achieved a 100% response rate with regard to gain or regain of 1 or more defined developmental milestones, which serves as the pivotal trial’s primary end point.² 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. The company characterized TSHA-102's safety profile as “well tolerated” in part A. In addition, in October 2025, Taysha announced that TSHA-102 had received breakthrough therapy designation from the FDA.

“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 an October 2025 statement.² “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.”

REFERENCES
1. Taysha Gene Therapies announces progress across TSHA-102 pivotal gene therapy program in Rett syndrome. News release. Taysha Gene Therapies, Inc. January 6, 2026. Accessed January 30, 2026. https://ir.tayshagtx.com/news-releases/news-release-details/taysha-gene-therapies-announces-progress-across-tsha-102-pivotal
2. 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 January 30, 2026. https://ir.tayshagtx.com/news-releases/news-release-details/taysha-gene-therapies-announces-fda-breakthrough-therapy