Taysha Gene Therapies Reports Positive Data from REVEAL Trials on TSHA-102 for Rett Syndrome

Taysha Gene Therapies, Inc. has released promising new data from their ongoing REVEAL Phase 1/2 trials evaluating the TSHA-102 gene therapy for Rett syndrome. Rett syndrome is a severe neurodevelopmental disorder caused by mutations in the MECP2 gene, leading to significant impairments in motor and cognitive functions, communication, and seizures, primarily affecting females. Currently, no therapies exist that address the genetic root cause of this disorder.

The trials consist of two cohorts: one for adolescents and adults, and another for pediatric patients. In the adolescent and adult cohort, significant long-term improvements were observed across various clinical domains, including motor skills, communication, autonomic function, and seizure control. Two adult patients with different severities of genetic mutations showcased durable enhancements in their conditions. One patient, treated with a low dose of TSHA-102, demonstrated the ability to sit unassisted for the first time in over ten years, normalized sleep patterns, and stabilized seizures. Meanwhile, the second patient experienced reduced hand stereotypies, improved breathing, and an 8.5-month seizure-free period while on 25% less anti-seizure medication.

The pediatric cohort also reported encouraging results. Initial data from the first two pediatric patients revealed early improvements in motor skills, communication, and developmental gains. The first pediatric patient gained the ability to stand up from a chair and walk up a stair, saw improvements in hand function and gross motor coordination, and increased visual reception and receptive language skills. The second pediatric patient demonstrated improved gait, speed, and stability, along with more seizure-free days.

Based on these promising outcomes, the Independent Data Monitoring Committee (IDMC) has approved the company’s request to advance to the second cohort (high dose) in the REVEAL pediatric trial, with dosing scheduled for the third quarter of 2024 after reviewing initial safety data from the adolescent and adult trials.

Sean P. Nolan, Chairman and CEO of Taysha, expressed optimism about the data, noting the broad clinical response and the durable improvements observed in both adult and pediatric patients. He emphasized that the results reinforce the potential of TSHA-102 to be transformative for Rett syndrome patients, offering a new hope for those affected by this debilitating disorder.

Dr. Elsa Rossignol, Principal Investigator of the REVEAL adolescent and adult trial, highlighted the well-tolerated nature of the treatment, with no serious adverse events or dose-limiting toxicities reported as of the 52-week and 36-week assessments for the first and second adult patients, respectively. She noted substantial improvements in movement, socialization, autonomic function, and seizure control, indicating the broad clinical benefits and durability of TSHA-102 in treating Rett syndrome's most advanced stages.

Pediatric patients, although facing challenges related to the immunosuppressive regimen, also showed well-tolerated responses with no serious adverse events related to TSHA-102. Dr. Colleen Buhrfiend, Assistant Professor of Pediatrics at RUSH University Medical Center, reported initial improvements in motor skills and communication in both pediatric patients, describing these changes as encouraging early signs of potential benefit.

The REVEAL Phase 1/2 trials are an open-label, dose-escalation and dose-expansion study evaluating the safety and preliminary efficacy of TSHA-102, administered via a single lumbar intrathecal injection. The trials are ongoing in the U.S. and Canada for adolescent and adult patients and in the U.S. and U.K. for pediatric patients. The trials aim to determine the maximum tolerated dose and evaluate the efficacy of TSHA-102 in improving clinical outcomes for Rett syndrome patients.

In summary, Taysha Gene Therapies' latest data on TSHA-102 showcases promising improvements across multiple clinical domains for Rett syndrome patients, highlighting the therapy’s potential to significantly alter the course of this challenging disorder.