FDA awards RMAT status to Taysha’s Rett syndrome gene therapy

Rett syndrome is a genetic disorder predominantly affecting girls, leading to severe cognitive and physical disabilities. Characterized by a loss of communication skills, developmental delays or regression, and motor and respiratory challenges, Rett syndrome is caused by mutations in the MECP2 gene, which plays a crucial role in brain development.

Taysha Gene Therapies has made significant strides in addressing this condition. The company recently secured a regenerative medicine advanced therapy (RMAT) designation from the US Food and Drug Administration (FDA) for its innovative gene therapy candidate, TSHA-102. This designation aims to fast-track the development and review process for regenerative treatments that can address, modify, or potentially cure serious health conditions.

TSHA-102 employs an AAV9 virus vector to deliver the MECP2 gene directly into the central nervous system. This approach targets the root cause of Rett syndrome, offering hope for a treatment that could address the genetic basis of the disorder. The RMAT designation was granted based on promising initial results from ongoing Phase I/II REVEAL clinical trials, which include both adult and pediatric patients. Early safety and efficacy data from the first three patients treated with a low dose of TSHA-102 were instrumental in this decision. The high-dose patient cohort results are anticipated in the second half of 2024.

In a strategic move in October 2022, pharmaceutical giant Astellas announced plans to invest in Taysha’s development programs for Rett syndrome and giant axonal neuropathy (GAN). This investment included an exclusive option to license two of Taysha’s clinical-stage programs: TSHA-102 for Rett syndrome and TSHA-120 for GAN. However, around a year later, Taysha decided to discontinue the TSHA-120 program following a Type C meeting with the FDA. The agency recommended a placebo-controlled study and long-term follow-up trial, prompting Astellas to forgo its licensing option for TSHA-120. Consequently, Taysha shifted its focus entirely to the TSHA-102 program.

According to forecasts from GlobalData’s Pharma Intelligence Center, TSHA-102 is expected to generate $650 million in sales by 2030. This potential underscores the significant market opportunity and the high unmet medical need for effective treatments for Rett syndrome. Taysha’s president and head of R&D, Sukumar Nagendran, emphasized the importance of the RMAT designation, stating that it highlights the therapeutic potential of TSHA-102 to transform the treatment landscape for Rett syndrome.

In a related development, Acadia Pharmaceuticals launched the first US FDA-approved drug for Rett syndrome, Daybue (trofinetide), in April 2023. This medication works by deactivating certain brain cells to prevent further neurodegeneration and injury-induced seizures. Despite this advancement, there is still no treatment available that directly addresses the genetic root of Rett syndrome, reinforcing the importance of continued research and development in this area.

Overall, the RMAT designation for TSHA-102 represents a significant milestone for Taysha Gene Therapies and offers renewed hope for patients and families affected by Rett syndrome. As the company progresses with its clinical trials, the medical community eagerly anticipates further developments that could bring a much-needed therapeutic option to those living with this challenging genetic disorder.