Taysha Cleared to Use Higher Dose in Adolescent and Adult Trial for Rett Syndrome Gene Therapy TSHA-102
Taysha Gene Therapies also announced additional updates on the TSHA-102 program for both adolescent adult patients and pediatric patients.
Sukumar Nagendran, MD
Taysha Gene Therapies has received approval from an Independent Data Monitoring Committee (IDMC)for a request to escalate to the higher dose cohort in its phase 1/2 REVEAL adolescent and adult clinical trial (NCT05606614) for TSHA-102, an investigational adeno-associated virus vector-based gene therapy, for the treatment of Rett syndrome.1
The approval allows Taysha to proceed to dose escalation in the trial early. The trial’s lower dose cohort previously treated 2 patients at a dose of 5.7x1014 total vg, and is now considered complete; updated clinical data from these patients is anticipated before the end of the first quarter of 2024.1,2 The company expects dosing of the first patient in the higher dose cohort, which will treat patients with 1x1015 total vg of TSHA-102, to take place in the second quarter of 2024. The higher dose cohort will include 3 patients in total, as per protocol. The company anticipates reporting initial safety and efficacy data from the higher dose cohort in the second half of 2024. Furthermore, Taysha also noted that it intends to expand the study, which began in Canada, into the United States. In line with this goal, it has submitted the adolescent and adult (age 12+ years) trial protocol to the FDA.
In addition to the aforementioned updates regarding the REVEAL adolescent and adult trial, Taysha also announced several updates regarding the separate phase 1/2 REVEAL Pediatric Study clinical trial (NCT06152237). The company reported that it has received IDMC approval to dose the second patient in the lower dose cohort (5.7x1014 total vg) of the pediatric study. This dosing is expected to take place within the first quarter of this year; the cohort is ultimately expected to treat 3 patients in total. Taysha also noted that it expects to announce initial safety and efficacy data from the lower dose cohort in mid-2024. Initial safety and efficacy data from the planned higher dose cohort, which will treat 3 patients per protocol at 1x1015 total vg, is expected in the second half of 2024.
“We have been quite encouraged by the initial safety and efficacy data demonstrated to date with TSHA-102 and are pleased that we are cleared to dose the second patient in our REVEAL phase 1/2 pediatric trial, and importantly, that the IDMC approved our request to proceed to dose escalation in our REVEAL phase 1/2 adolescent and adult trial earlier than planned,” Sean P. Nolan, the chairman and chief executive officer of Taysha, said in a statement. “Advancing to the high dose cohort accelerates our ability to further inform our clinical development and regulatory plan for Part B of the study by at least a quarter. Additionally, we believe expanding our ongoing REVEAL adolescent and adult trial in Canada into the US will further support our goal to evaluate TSHA-102 across a broad range of ages and stages of patients with Rett syndrome. We are pleased with the progress we’ve made and remain focused on evaluating TSHA-102 as a potential treatment option for patients and families living with Rett syndrome.”
In December 2023, about a month before Taysha announced the dosing of the first pediatric patient with TSHA-102, CGTLive® spoke with Sukumar Nagendran, MD, the president and head of research and development at Taysha, about the results seen in the first 2 adult patients to receive the gene therapy.3 Nagendran emphasized the surprising efficacy results seen in these patients.
“The first patient that we dosed was 20 years of age and had severe Rett syndrome in stage 4, and most of us are very surprised of because of the clinical response that we saw,” Nagendran said in the interview. “Most of us, including the experts said, ‘You're not going to see a clinical response, get the safety data and go and move into the pediatric population.’ But what we noticed in the first patient was within 7 to 10 days there was a positive response on motor function and developmental milestones.”
