Taysha Doses Second Patient With Rett Syndrome With TSHA-102, per IDMC Recommendation

The second patient has been dosed in the phase 1/2 REVEAL clinical trial (NCT05606614) evaluating Taysha Gene Therapies’ TSHA-102, an investigational adeno-associated virus (AAV) vector-based gene therapy, for the treatment of adult patients with Rett syndrome.¹ The dosing was carried out in accordance with a recommendation to proceed made by the trial’s Independent Data Monitoring Committee (IDMC) in July 2023.²

Both the patients dosed in the study received the lower of the 2 doses that Taysha is evaluating in the trial.^1,2 The company intends to treat 1 additional patient at this dose level before the end of 2023; at that point, enrollment in the low-dose cohort would be completed. Both patients received the treatment at CHU Sainte-Justine, the Université de Montréal Mother and Child University Hospital Center in Montreal, Canada.

“Dosing the second adult patient in the REVEAL phase 1/2 adult trial in Canada marks important progress in the ongoing clinical evaluation of TSHA-102 for Rett syndrome,” Sukumar Nagendran, MD, the president and head of research and development, at Taysha, said in a statement.¹ “The enthusiasm for a potential disease-modifying therapy among the Rett syndrome community is encouraging, and we remain focused on further evaluating the therapeutic potential of TSHA-102 in adults and expanding the clinical evaluation to pediatric patients with this devastating disease. We look forward to reporting initial clinical data on the second adult patient and providing an update on the first adult patient in the low-dose cohort at our quarterly earnings conference call in mid-November, following the prespecified IDMC review.”

The IDMC’s recommendation to dose the second patient was made following a review of results from the dosing of the first patient. In June 2023, Taysha had announced that the first patient had been discharged from the hospital in accordance with study protocol and had completed several follow-up visits.³ 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.²

The following month, Taysha reported initial results from the first patient’s treatment.⁴ These included findings that, 4 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.

Taysha has stated that the FDA has cleared its investigational new drug application for the gene therapy to be assessed in pediatric patients with Rett syndrome in the United States.¹ Dosing of the first pediatric patient in this trial is expected in the first quarter of 2024. Taysha also notes that it has submitted a clinical trial application (CTA) to the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA) for a trial in pediatric patients. The company expects to hear back from the MHRA about the CTA before the end of the year. TSHA-102 has received fast track designation, orphan drug designation (ODD), and rare pediatric disease designation from the FDA and ODD from the European Commission.^1,5

Earlier this month, Taysha noted that it would be further prioritizing development of TSHA-102 in light of its discontinuation of development on its lead clinical candidate, TSHA-120, an investigational AAV vector-based gene therapy that was being evaluated in an open-label phase 1/2 clinical trial (NCT02362438) for the treatment of giant axonal neuropathy.⁶ Taysha’s decision to discontinue development of TSHA-120 was made after the company obtained feedback from a Type C meeting with the FDA that was related to the roadmap to approval for the gene therapy.

“This strategic program prioritization is expected to extend our cash runway into the fourth quarter of 2025 to support the continued clinical development of TSHA-102 in Rett syndrome, a rare neurodevelopmental disorder with no approved treatments that target the genetic root cause of the disease,” Sean P. Nolan, the chairman and chief executive officer of Taysha, said in a statement at the time of the announcement.⁶ 

REFERENCES
1. Taysha Gene Therapies announces second patient dosed with TSHA-102 in the REVEAL phase 1/2 adult trial for the treatment of Rett syndrome. News release. September 26, 2023. Accessed September 29, 2023. https://ir.tayshagtx.com/news-releases/news-release-details/taysha-gene-therapies-announces-second-patient-dosed-tsha-102
2. 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 September 29, 2023. https://ir.tayshagtx.com/news-releases/news-release-details/taysha-gene-therapies-announces-positive-recommendation
3. Taysha Gene Therapies provides clinical updates for investigational programs TSHA-120 in giant axonal neuropathy (GAN) and TSHA-102 in Rett syndrome at R&D day. News release. Taysha Gene Therapies, Inc. June 28, 2023. Accessed September 29, 2023. https://ir.tayshagtx.com/news-releases/news-release-details/taysha-gene-therapies-provides-clinical-updates-investigational
4. Taysha Gene Therapies reports initial clinical data from first adult Rett syndrome patient dosed in reveal phase 1/2 trial and provides corporate update with second quarter 2023 financial results. News release. Taysha Gene Therapies, Inc. August 14, 2023. Accessed September 29, 2023. https://ir.tayshagtx.com/news-releases/news-release-details/taysha-gene-therapies-reports-initial-clinical-data-first-adult
5. 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 September 29, 2023. https://ir.tayshagtx.com/news-releases/news-release-details/taysha-gene-therapies-announces-fast-track-designation-granted
6. Taysha Gene Therapies provides update on TSHA-120 program in giant axonal neuropathy (GAN). News release. Taysha Gene Therapies, Inc. September 19, 2023. Accessed September 29, 2023. https://ir.tayshagtx.com/news-releases/news-release-details/taysha-gene-therapies-provides-update-tsha-120-program-giant-0