FDA Grants Fast Track Designation to TSHA-102 as Potential Rett Syndrome Therapy


TSHA-102, an adeno-associated virus vector-based gene therapy for Rett Syndrome, has also received Orphan Drug and Rare Pediatric Disease designations from the FDA.

Sukumar Nagendran, MD, president and head of R&D at Taysha

Sukumar Nagendran, MD

In recent news, the FDA granted Fast Track Designation to Taysha Gene Therapies’ TSHA-102, an adeno-associated virus (AAV) vector gene transfer therapy, for the treatment of Rett syndrome.1 The gene therapy utilizes a novel miRNA-Responsive Auto-Regulatory Element (miRARE) platform designed to regulate cellular MECP2 expression, otherwise known as the root genetic cause of Rett syndrome.

Currently, the agent is being investigated in the Canadian-based REVEAL phase 1/2 trial (NCT05606614) of adult patients with Rett syndrome. The company also recently announced that the FDA has cleared its investigational new drug application for the agent to be assessed in pediatric patients with the condition and expects to dose the first pediatric patient in the first quarter of 2024.

“We are pleased to receive FTD from the FDA, which underscores the significant unmet medical need in patients with Rett syndrome and the potential of TSHA-102 to serve as a meaningful treatment option,” Sukumar Nagendran, MD, president and head of R&D at Taysha said in a statement.1 “Initial data from the first adult patient in Canada with severe disease dosed with TSHA-102 is encouraging, and we expect to dose the second patient in our ongoing REVEAL phase 1/2 adult trial in the current quarter. We look forward to expanding the clinical evaluation to earlier stages of disease progression following recent FDA clearance to initiate clinical development of TSHA-102 in pediatric patients in the United States.”

The company recently announced positive data from a single patient in the REVEAL trial showing that treatment with THSA-102 in low doses was safe, with efficacy observed in several key measures 4 weeks posttreatment. Findings showed a safe and tolerable profile with no treatment-emergent serious adverse events as of the 6-week posttreatment assessment.

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Investigators observed no quantifiable seizure events through 5 weeks and no marked changes in the Revised Motor Behavior Assessment, a 24-question clinician-reported scale measuring disease behaviors of Rett syndrome. At 4 weeks, the treated patient showed efficacy in key measures of Clinical Global Impression (CGI)-Improvement scale adapted to Rett syndrome, CGI-Severity scale, and Rett Syndrome Behavior Questionnaire.

In addition to showing a positive safety and tolerability profile, treatment with the therapy resulted in improvements in multiple domains, including vocalization with increased social interest. The treated individual also improved autonomic function, as demonstrated by enhanced breathing patterns and sleep quality/duration. Furthermore, investigators observed positive benefits in gross motor skills, with the patient showing a gained ability to sit unassisted for 3 minutes, and fine motor skills, as the patient gained the ability to hold an object, unclasp her hands, and use her fingers to touch a screen.

The positive patient data comes weeks after the company announced it will continue dosing the gene therapy in a second patient based on recommendations from an Independent Data Monitoring Committee (IDCM). The recommendation from the IDCM was specifically based on the prespecified examination results from the first patient that had reached the end of a posttreatment evaluation period, which lasted 42 days. Continued dosing for the adult patients is expected to occur in the second half of 2023, with further updates on available clinical data expected quarterly.2

“Rett syndrome is a devastating neurodevelopmental disorder that can lead to motor and respiratory impairment, loss of communication, and ultimately shortened life expectancy. Currently, there are no approved disease-modifying therapies that treat the genetic root cause of the disease,” Rumana Haque-Ahmed, senior vice president of Regulatory Affairs at Taysha said in a statement.1 “Receiving FTD for important aspects of the disease is a critical milestone that furthers our ability to accelerate the development of TSHA-102 with the potential to address a serious condition and significant unmet medical need in patients living with this devastating disease. We look forward to having continued discussions with the FDA, with the goal of bringing TSHA-102 to patients as safely and expeditiously as possible.”

1. Taysha Gene Therapies Announces Fast Track Designation Granted by U.S. FDA for TSHA-102 in Rett Syndrome. News Release. Taysha Gene Therapies. Published August 24, 2023. Accessed August 24, 2023. https://ir.tayshagtx.com/news-releases/news-release-details/taysha-gene-therapies-announces-fast-track-designation-granted
2. Taysha Gene Therapies reports initial clinical data from first adult Rett syndrome patient dosed in REVEAL phase ½ trial and provides corporate update with second quarter 2023 financial results. News release. Taysha Gene Therapies. August 14, 2023. Accessed August 24, 2023. https://finance.yahoo.com/news/taysha-gene-therapies-reports-initial-110200128.html
3. Taysha Gene Therapies announces positive recommendation from independent data monitoring committee of REVEAL phase 1/2 trial in Rett syndrome. News release. Taysha Gene Therapies, Inc. July 31, 2023. Accessed August 24, 2023. https://ir.tayshagtx.com/news-releases/news-release-details/taysha-gene-therapies-announces-positive-recommendation
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