Rett Syndrome Gene Therapy TSHA-102 Demonstrates Improvements in First Patient Dosed
In terms of safety, Taysha stated that TSHA-102 was well-tolerated and that at 6 weeks after dosing no treatment-emergent serious adverse events had occurred.
Taysha Gene Therapies’ TSHA-102, an investigational adeno-associated virus (AAV) vector-based gene therapy for the treatment of Rett syndrome, has demonstrated safety and efficacy in the first patient treated in the phase 1/2 REVEAL clinical trial (NCT05606614).1
Four weeks following the administration of TSHA-102, the patient demonstrated a score of 2 (“much improved”) on a version of the Clinical Global Impressions–Improvement scale adapted to Rett syndrome, an improvement to a score of 5 (“markedly ill”) from a baseline score of 6 (“severely ill”) on the Clinical Global Impressions–Severity scale, and an improvement to a score of 29 from a baseline score of 52 on the Rett Syndrome Behavior Questionnaire. Conversely, on the Revised Motor Behavior Assessment, there were no marked changes at 4 weeks after dosing.
At 6 weeks after administration of the gene therapy, observations of improvement in autonomic function, sleep quality and duration, normalization of nighttime behavior, and social interest were reported. Gained abilities to sit unassisted for 3 minutes, to hold an object, to unclasp hands, and to use fingers to touch a screen were also noted. At 5 weeks after treatment with TSHA-102, there had been no quantifiable seizure events recorded.
“The efficacy response observed following treatment with TSHA-102 in the first adult with an advanced stage of Rett syndrome is promising,” Elsa Rossignol, MD, FRCP, FAAP, associate professor neuroscience and pediatrics at CHU Sainte-Justine, affiliated to the Université de Montréal, and the principal investigator of REVEAL, said in a statement.1 “Prior to treatment, the patient was in a constant state of hypertonia, had limited body movement, required constant back support, and had lost fine and gross motor function early in childhood. Following treatment, we have observed improvements in breathing patterns, vocalization, and motor skills. The patient was able to sit unassisted for the first time in over a decade, and she demonstrated the ability to unclasp her hands and hold an object steadily for the first time since infancy.”
“I believe that the patient achieving these milestones so early in treatment, coupled with the improvements in breathing patterns and quality of sleep that we have observed, are highly encouraging and support the potential of TSHA-102. I am honored to work with the Rett syndrome community and help patients and families suffering from this devastating disease,” Rossignol said.
In terms of safety, Taysha stated that TSHA-102 was well-tolerated and that at 6 weeks after dosing no treatment-emergent serious adverse events had occurred.1 In July 2023, the trial’s Independent Data Monitoring Committee (IDMC) recommended that Taysha proceed with dosing a second patient in REVEAL.2 The IDMC’s recommendation was based on a prespecified examination of clinical results carried out after the first patient had reached the end of a posttreatment evaluation period lasting 42 days.
Taysha anticipates that the second patient will receive treatment with TSHA-102 within the third quarter of 2023. The REVEAL trial, which is being conducted under a clinical trial application (CTA) cleared by Health Canada in March of last year, is currently taking place at a single site in Canada and is recruiting women aged 18 years or older. Taysha recently received clearance from the FDA for an investigational new drug application to evaluate TSHA-102 in children with Rett syndrome in the United States and has submitted a CTA to the United Kingdom’s Medicines and Healthcare products Regulatory Agency, also aimed a trial for children.1
Alongside the announcement of the clinical results, the company also reported that it has entered a securities purchase agreement for a private placement financing (PIPE) lead by RA Capital Management.3 Taysha anticipates that the sale of common stock and prefunded warrants to purchase shares of common stock under the PIPE will results in gross proceeds approximated at $150 million prior to relevant deductions.
“We are pleased by the support from this prestigious group of new and existing investors, which we believe highlights the enthusiasm of the early clinical readout of the first patient treated in our REVEAL trial and reinforces the potential of gene therapy to transform the lives of patients suffering from devastating diseases,” Sean P. Nolan, the chairman and CEO of Taysha, said in a statement.3 “We expect that the net proceeds from the PIPE, together with our existing cash and cash equivalents, will extend our cash runway into the third quarter of 2025 to primarily support the clinical development of TSHA-102 in Rett syndrome and provide support for TSHA-120 program activities in giant axonal neuropathy, working capital, and other general corporate purposes. With this capital infusion, we believe we are well positioned to continue to execute across key program milestones.”
