TSHA-102 Gets FDA Fast Track Designation in Rett Syndrome


TSHA-102 has previously received orphan drug and rare pediatric disease designations from the agency and is being investigated in the REVEAL phase 1/2 trial (NCT05606614).

A version of this article originally appeared on our sister site, NeurologyLive.

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

Sukumar Nagendran, MD

The FDA has given a fast track designation to Taysha Gene Therapies’ adeno-associated virus (AAV) vector gene transfer therapy, TSHA-102, for the treatment of Rett syndrome.1 The agent is currently being assesed in the Canadian-based phase 1/2 REVEAL trial (NCT05606614) in adult patients with Rett syndrome.

“We are pleased to receive [fast track designation] 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 Nagendran continued by noting that the data from the first adult patient in REVEAL was "encouraging" and that the company anticipates dosing the second patient in the third quarter of 2023. "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," he said.

The company recently announced those positive data from that 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.

The gene therapy uses 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. Taysha Gene Therapies 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.

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In those data, the investigators observed no quantifiable seizure events after 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 the 4-week mark, 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.

Treatment with the therapy also 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 were announced weeks after another announcement that Taysha would 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

Rumana Haque-Ahmed, senior vice president of Regulatory Affairs at Taysha said in a statement,1 “Receiving [fast track designation] 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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