Pivotal trial of Rett gene therapy TSHA-102 now underway, and recruiting
REVEAL testing whether patients can gain or regain developmental milestones
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The pivotal REVEAL clinical trial — a Phase 3 study testing Rett syndrome gene therapy candidate TSHA-102 — has dosed its first participant, according to an update from treatment developer Taysha Gene Therapies.
REVEAL (NCT05606614) is expected to enroll 15 girls and young women with a confirmed genetic diagnosis of Rett syndrome. All participants will receive one-time treatment with TSHA-102, Taysha’s lead clinical program for Rett.
The trial’s goal is to assess whether the participants — who range in age from 6 to 21 — gain or regain at least one of 28 developmental milestones that Rett patients generally do not achieve in the absence of treatment.
Participants are still being recruited at six sites across the U.S. and Canada.
“Dosing the first patient in our REVEAL pivotal trial last quarter represents a significant milestone in the development of TSHA-102 for Rett syndrome, and enrollment is further advancing across multiple sites,” Sean P. Nolan, chairman and CEO of Taysha, said in a company press release, which noted that the study aims to provide “longer-term safety and efficacy data” on the experimental therapy.
Rett syndrome is caused primarily by mutations in the gene MECP2. TSHA-102 is designed to deliver a healthy version of this gene to cells in the nervous system, alongside molecular machinery that fine-tunes the gene’s activity to prevent toxic overactivation. The therapy is delivered directly into the spinal canal, known as an intrathecal injection.
Developer will use trial data to seek US approval of Rett gene therapy
TSHA-102 has previously been tested in a Phase 1/2 program, which included an earlier iteration of REVEAL as well as another study (NCT06152237) conducted in girls aged 5 to 8.
Interim data from patients treated in these early trials indicated that the gene therapy was generally safe and led to improvements in communication abilities, social skills, and motor function. Further updates from patients in the earlier trials are expected in the coming months, according to Taysha.
In addition to the ongoing REVEAL trial, Taysha is planning to launch another trial called ASPIRE, which will test one-time TSHA-102 treatment in three girls, ages 2 to 3, with Rett syndrome. The company stated that both trials are expected to wrap up dosing by the end of June.
“We expect to complete dosing across our REVEAL and ASPIRE trials in the second quarter of 2026,” Nolan said. “With an estimated 15,000 to 20,000 patients affected by Rett syndrome across the U.S., [the] EU, and [the] U.K. and compelling REVEAL Part A clinical data, we see a significant opportunity to redefine the treatment paradigm for this devastating disease with high unmet need.”
Our planned BLA [biologics license application] submission will include at least three months of safety data from three patients aged [2 years to younger than 4] in the ASPIRE trial to support a broad label for patients aged [2] years and older with Rett syndrome.
Taysha is planning to use data from both REVEAL and ASPIRE as the basis for its request to the U.S. Food and Drug Administration (FDA) seeking approval of TSHA-102 for Rett syndrome. The company said it has received written communication from the FDA that positive safety data from the ASPIRE trial, with at least three months of follow-up, could help support an application seeking approval of the therapy in patients as young as 2.
“As we progress pivotal development, we continue to maintain consistent and productive dialogue with the FDA,” Nolan said. “Importantly, we recently reached written alignment with the FDA that our planned BLA [biologics license application] submission will include at least three months of safety data from three patients aged [2 years to younger than 4] in the ASPIRE trial to support a broad label for patients aged two years and older with Rett syndrome.”
Nolan said that development, along with “the alignment on a six-month interim analysis for our REVEAL pivotal trial, streamlines our path toward BLA submission for TSHA-102.”
