Taysha gets green light for dose escalation in TSHA-102 trial
Gene therapy for Rett now being tested in children, adults in REVEAL study
Taysha Gene Therapies has received the needed approval to move forward with dose escalation in its Phase 1/2 trial testing TSHA-102, its gene therapy candidate for Rett syndrome, in adolescents and adults, the company announced.
That green light from the study’s independent data monitoring committee (IDMC) — a group of experts overseeing the ongoing REVEAL clinical trial (NCT05606614) — means that Taysha can now step up to the treatment’s second and highest planned dose for testing. Use of that higher dose is expected to happen in the second quarter of the year.
The IDMC also approved dosing of the second child in the low-dose group of the pediatric version of REVEAL (NCT06152237), which began dosing earlier this year. The second child may be dosed this month, with initial data expected by mid-year.
The dose escalation go-ahead came after the monitoring committee reviewed available data from patients who had already received TSHA-102. Data from the first two adults treated showed that the gene therapy was well tolerated, and that it helped with breathing, sleeping, social interest, and gross and fine motor skills.
“We have been quite encouraged by the initial safety and efficacy data demonstrated to date with TSHA-102,” Sean P. Nolan, Taysha’s chairman and CEO, said in a company press release.
Taysha now seeking permission to expand 1 trial to US
According to Nolan, Taysha is “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.”
The company also plans to expand clinical testing into the U.S. for adult and adolescent patients following its submission of a clinical protocol for ages 12 and older to the U.S. Food and Drug Administration. That would allow more older patients to be tested with TSHA-102.
“Expanding our ongoing REVEAL adolescent and adult trial in Canada into the U.S. will further support our goal to evaluate TSHA-102 across a broad range of ages and stages of patients with Rett syndrome,” Nolan said.
In nearly all cases, symptoms of Rett are caused by mutations in the MECP2 gene, which provides instructions for producing a protein that’s needed for normal brain development.
Gene therapy for Rett syndrome aims to deliver a healthy copy of MECP2 into cells so that they can produce that protein on their own. Some cells may already produce some of it. Therefore, it’s important to tune its levels warily to avoid harmful effects, according to the researchers.
TSHA-102 combines miniMECP2 — a shorter but working version of the MECP2 gene — with miRARE, a technology that allows control of gene activity. This is expected to prevent too much protein from being produced.
Advancing to the high dose cohort [group] accelerates our ability to further inform our clinical development and regulatory plan for Part B of the study by at least [three months].
Part A of the two dose-escalation clinical trials is ongoing in a small number of patients to determine the highest dose of TSHA-102 that does not cause harmful side effects. The experimental gene therapy is given as a single injection into the spinal canal at the lower back.
Of two doses — 5.7E14 and 1E15 vector genomes — one will be selected for dose expansion in Part B, in which a larger number of patients will receive TSHA-102. Initial data from the high-dose groups are expected later this year, both in children and in adolescents and adults.
“Advancing to the high dose cohort [group] accelerates our ability to further inform our clinical development and regulatory plan for Part B of the study by at least a quarter,” or at least three months, Nolan said.
Both clinical trials — the one for adults is being conducted at a site in Montréal — are listed as still recruiting.
The pediatric version, which is enrolling children ages 5 to 8 for Part A, and as young as age 3 for Part B, has one site open in Chicago, with plans to open several more sites in the U.S. and the U.K.
About the Author
