The U.S. Food and Drug Administration (FDA) has cleared Atamyo Therapeutics to proceed with a Phase 1b clinical trial of ATA-200, a gene therapy candidate for limb-girdle muscular dystrophy type 2C/R5 (LGMD2C/R5), in children. This marks a significant milestone as ATA-200 becomes the first potential treatment for this specific form of LGMD to enter clinical development in the United States. The trial is set to begin by the end of the year, with the first U.S. center expected to open soon.
Trial Design and Objectives
The Phase 1b trial (NCT05973630) is an open-label, dose-escalation study designed to evaluate the safety and tolerability of a single intravenous infusion of ATA-200 in approximately six children aged 6 to 13 years. The study will be conducted across multiple sites, including locations in the U.S., Paris, and Milan. The primary objectives include assessing the safety profile of ATA-200 and determining the optimal dose for future clinical trials. Secondary endpoints will focus on evaluating preliminary signs of efficacy. The trial is being funded in the U.S. by the Dion Foundation for Children with Rare Diseases.
Addressing LGMD2C/R5
LGMD is a group of genetic disorders characterized by progressive muscle weakness primarily affecting the shoulders and hips. LGMD2C/R5 is caused by mutations in the SGCG gene, which encodes the gamma-sarcoglycan protein. This protein is crucial for stabilizing muscle fibers and preventing muscle damage. Deficiency of gamma-sarcoglycan leads to muscle weakness, which typically manifests in childhood, and can also result in heart complications. There is currently no cure for LGMD2C/R5, and treatment options are limited to managing symptoms and providing supportive care.
ATA-200: A Gene Therapy Approach
ATA-200 is designed to deliver a functional copy of the SGCG gene to muscle cells using an adeno-associated virus (AAV) vector. By restoring the production of gamma-sarcoglycan, the therapy aims to improve muscle fiber stability and function, thereby slowing or halting the progression of the disease. The FDA has granted ATA-200 orphan drug status and rare pediatric disease designation for LGMD2C/R5, which are intended to expedite the therapy's development and regulatory review.
Dosage and Monitoring
The Phase 1b trial will involve a sequential, dose-escalation design. The first three participants will receive a low-dose infusion of ATA-200, followed by a one-month safety data review. If deemed safe, the next three participants will receive a higher-dose infusion. The children will be monitored for at least six months to assess safety outcomes and to determine the optimal dose for future studies. Following this initial period, all participants will be followed for an additional 4.5 years to monitor long-term safety and efficacy.
Expert Commentary
"This IND clearance is an important step to bring ATA-200 to U.S. children suffering from this highly debilitating disease," said Sophie Olivier, MD, chief medical officer of Atamyo. Stéphane Degove, Atamyo’s CEO, added, "We are proud to be the first treatment for LGMD-2C/R5 to enter into clinical development in the U.S. and we are committed to opening the first U.S. center before year-end."
