FDA Tells Taysha It Should Increase the Number of Patients in GAN Gene Therapy Study

Rare Daily Staff

Taysha Gene Therapies, in providing an update on its program for giant axonal neuropathy, said the U.S. Food and Drug Administration recommended that it increase the number of participants being dose in a double-blind, placebo-controlled design to support submission for regulatory approval of the experimental gene therapy TSHA-120.

Giant axonal neuropathy (GAN) is a rare inherited genetic disorder that affects both the central and peripheral nervous systems and is caused by loss-of-function mutations in the gene coding for gigaxonin. Many children with GAN show symptoms and features before the age of five, including progressive scoliosis, contractures, atrophy of the spinal cord, giant axons—also known as nerve fibers—and abnormalities of the white matter in the brain. Currently, there are no approved treatments for GAN, which often results in death for patients in their late teens or early twenties.

TSHA-120, an intrathecally dosed AAV9 gene replacement therapy delivering the gene gigaxonin for the treatment of GAN, is currently being evaluated in an ongoing phase 1/2 clinical trial. The disease is caused by loss-of-function mutations in the gene coding for gigaxonin, which results in dysregulation of intermediate filament turnover, an important structural component of the cell. Children with GAN present before the age of five with symptoms including unsteady gait, frequent falls, and motor weakness. Currently, there are no approved treatments for GAN, which results in death for patients in their late teens or early twenties. TSHA-120 has received Orphan Drug and Rare Pediatric Disease designations from FDA and Orphan Drug designation from the European Commission.

In October 2022, Astellas Pharma took a 15 percent stake in Taysha for $50 million and an exclusion option on TSHA-120 and TSHA-102, Taysha’s experimental gene therapy for Rett syndrome.

“For our GAN program, we received the formal FDA meeting minutes and recently submitted follow up questions to clarify some of their recommendations including the feasibility of a proposed study design and the totality of evidence required for BLA submission,” said Sean Nolan, chairman and CEO of Taysha. “Their feedback will help inform next steps for the program in this ultra-rare indication with no approved treatments.”

Taysha said it is awaiting a response from the FDA on follow up the questions it submitted on recommended design and totality of evidence required for application for marketing approval.

Photo: Sean Nolan, chairman and CEO of Taysha