Atamyo Therapeutics has announced significant progress in its gene therapy programs targeting limb-girdle muscular dystrophy (LGMD). The company has completed patient recruitment for the dose-escalation portion of its Phase 1b clinical trial (ATA-001-FKRP) evaluating ATA-100, an investigational adeno-associated virus (AAV) vector-based gene therapy for fukutin-related protein (FKRP) limb-girdle muscular dystrophy type 2I/R9 (LGMD2I/R9). Furthermore, Atamyo has submitted an Investigational New Drug (IND) application to the FDA for ATA-200, an investigational AAV vector-based gene therapy intended to treat γ-sarcoglycan (SGCG)-related LGMD Type 2C/R5 (LGMD2C/R5).
ATA-100 for LGMD2I/R9
The Phase 1b study of ATA-100 (ATA-001-FKRP) is being conducted across multiple sites in Denmark, France, and the United Kingdom. Initial results from the first cohort of patients treated with ATA-100 have been promising. According to Atamyo, the first three patients experienced a marked decline in creatine kinase levels, improved velocity maintained a year after treatment, vanishing symptoms including cramps and myalgia, and improved quality of life. "The first patients dosed with ATA-100 have experienced promising functional results and the gene therapy has been overall well tolerated in all treated patients with no unexpected safety signal," said Stephane Degove, the chief executive officer and cofounder of Atamyo.
ATA-200 for LGMD2C/R5
Atamyo's IND submission for ATA-200 aims to expand the multicenter, open-label Phase 1b clinical trial (NCT05973630) to the United States. The trial has already been cleared in Italy and France. The FDA has granted rare pediatric disease designation to ATA-200, a status that encourages the development of therapies for rare diseases. The company anticipates dosing patients in the ATA-200 trial before the end of 2024. The Dion Foundation has partnered with Atamyo Therapeutics to expand the clinical trial of ATA-200 into the U.S. The Phase 1b study is designed to evaluate the safety, efficacy, and pharmacological and immunological properties of ATA-200.
LGMD2C/R5 is caused by mutations in the SGCG gene, which provides instructions for producing the protein gamma-sarcoglycan. Symptoms of LGMD typically start in early childhood and include progressive muscle weakness and the loss of walking abilities before adulthood. Also, about half of LGMD2C/R5 patients have dilated cardiomyopathy, a condition of the heart muscle. ATA-200 uses a modified, harmless adeno-associated viral vector (AAV) to deliver an engineered version of the SGCG gene to cells and restore the function of the sarcoglycan complex. In animal models, a single administration of the therapy was well tolerated, and was shown to reverse disease symptoms and normalize levels of biomarkers.
Significance for LGMD Patients
Both LGMD-2I/R9 and LGMD-2C/R5 are rare diseases with no curative treatment options currently available. Existing treatments are largely supportive. These advancements in gene therapy offer hope for patients suffering from these debilitating conditions. "We are thrilled to have completed the recruitment of the dose escalation phase of our phase 1b study of ATA-100," said Sophie Olivier, MD, the chief medical officer of Atamyo. "Data of the dose escalation will serve at selecting the dose to carry over in the pivotal phase of the study."
