Taysha, FDA agree on next steps of REVEAL trial for Rett gene therapy
Study's Part B will test TSHA-102's safety, efficacy at identified optimal dose
Taysha Gene Therapies has reached an agreement with the U.S. Food and Drug Administration (FDA) on the design and next steps to start the pivotal Part B of its ongoing Phase 1/2 REVEAL trial program, which is evaluating TSHA-102 in children, adolescents, and adults with Rett syndrome.
Part B will assess the safety and efficacy of Taysha’s investigational gene therapy at the optimal dose identified in Part A, which included treatment with low and high doses, in a larger group of patients. The agreement will let Taysha submit the trial protocol and statistical analysis plan as an amendment to its existing investigational new drug (IND) application, without needing a formal end-of-phase meeting. These meetings are typically held to review earlier clinical results and align on the design and plans for the next phase.
By skipping this step, Taysha expects to expedite the start of the next phase of REVEAL and accelerate the pathway toward TSHA-102’s potential registration and approval. The company expects to submit the amendment in the second quarter of this year.
Assessing TSHA-102’s benefit in Rett syndrome
This advancement was achieved after discussions that were part of the Regenerative Medicine Advanced Therapy (RMAT) designation, which was granted to TSHA-102 last year. The designation, given to regenerative medicines that might treat serious or life-threatening conditions, came after early signs of clinical benefit in the first three participants treated at the low dose in Part A.
“We are pleased with the significant regulatory and clinical progress across our TSHA-102 program in clinical evaluation for children, adolescents, and adults suffering from Rett syndrome. We believe our interactions with the U.S. FDA under the RMAT mechanism have consistently been productive and continue to support a clear path to registration,” Sean P. Nolan, chairman and CEO of Taysha, said in a company press release. “We believe the progress we’ve made with the FDA on our registrational pathway supports the strength of our data-driven approach and further enables our goal to bring TSHA-102 to patients with this devastating disease as expeditiously as possible.”
The REVEAL program consists of two parallel Phase 1/2 studies to assess the safety, tolerability, and initial efficacy of TSHA-102 in up to 20 children ages 5-8, in the pediatric study (NCT06152237), and up to 18 women and teens, ages 12 and older, in the adult study (NCT05606614). In Part A of both studies, participants are receiving a low or high dose to identify the optimal dose for further evaluation.
Administered into the spinal canal, or intrathecally, TSHA-102 uses a viral vector to deliver to brain cells a shortened, yet working copy of the MECP2 gene, which is defective in most Rett cases. The gene encodes the MeCP2 protein, a key regulator of brain development and function. The therapy also incorporates a technology called miRARE, which modulates gene expression to ensure the therapeutic protein is produced at healthy, nontoxic levels.
Interim data shared last year from the low-dose group showed safety and clinical benefits in both adults and children, with gains in multiple domains, including motor skills, communication, and social interaction.
Ten patients have been treated so far across both studies, six at the high dose and four at the low dose. TSHA-102 continues to show a favorable safety profile at both levels, with no treatment-related serious adverse events or dose-limiting toxicities reported.
Taysha plans to share further updates, including new safety and efficacy data, along with updates on the pivotal Part B trial design at the International Rett Syndrome Foundation (IRSF) Rett Syndrome Scientific Meeting set for June 9-11 in Boston.
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