First Patient Dosed in Limb-Girdle Muscular Dystrophy Gene Therapy Trial


The 2-stage, multicenter clinical trial will recruit approximately 39 patients who have been diagnosed with LGMDR9.

The first patient with FRKP-related limb-girdle muscular dystrophy type 2I/R9 (LGMD2I/R9) has been treated with Atamyo Therapetuics’ ATA-100 (GNT0006), an investigational gene therapy, in a phase 1/2 clinical trial (EudraCT 2021-004276-33, NCT05224505).1

ATA-100 is intended to deliver a functional copy of the human FKRP transgene, the disease-targeted gene, via an adeno-associated virus (AAV) vector. It is administered as a single-dose. It was previously announced in February 2022 that ATA-100 had received orphan drug designation from the FDA for the treatment of LGMD/R9 and from the European Medicines Agency for the treatment of LGMD.2

"This is an exciting milestone for our company but most importantly, if this clinical trial is successful, it could have a life-changing impact for patients affected by LGMD-R9," Stephane Degove, chief executive officer and co-founder, Atamyo Therapeutics, said in a statement.1

The 2-stage, multicenter clinical trial will recruit approximately 39 patients between the ages of 16 and 99 years who have been diagnosed with LGMDR9, confirmed based on clinical presentation and genotyping. Participants are required to be ambulant and to have moderate diaphragmatic muscle impairment. Participants must additionally be able to perform a 10-meter walk test (10MWT) within 30 seconds with unilateral or bilaterial help and must be able to rise from a standard-height chair with or without arm support. Patients with cardiomyopathy or detectable serum neutralizing antibodies against AAV9 will be excluded from the study, as will patients who require any form of respiratory assistance. Additional exclusion criteria relate to patient health-status and previously received treatments.

The first stage, an open-label dose escalation phase, will treat 6 patients. The participants will receive a dose of ATA-100 at either 9x1012 vg/kg (cohort 1) or 2.7x1013 vg/kg (cohort 2) via a single intravenous injection. In the second stage, 22 patients will be randomly assigned to an experimental arm while 11 patients will be randomly assigned to a placebo comparator arm. Patients in the experimental arm will receive ATA-100 at the selected dose from stage 1, and will receive a placebo 1 year after. Patients in the placebo comparator arm will receive a placebo at Day 0, and will receive the selected dose of ATA-100 a year later. The study’s primary end point is the percent change from baseline in forced vital capacity at 1 year. Secondary end points include a 10MWT, a Timed Up and Go test, a 2-minute walk distance test, the change from baseline in the North Star Assessment for Neuromuscular Disorders (NSAD) scale, cardiac and muscle MRIs, quantifications of FKRP positive muscle fibers and percentage of glycoslyation determined via muscle biopsies, and responses to Quality of Life in genetic Neuromuscular Disease and ACTIVLIM quality of life assessments. The study will recruit patients at locations in Denmark, France, and the United Kingdom. It has an estimated primary completion date of October 2025 and an estimated completion date of October 2030.

"LGMD-R9 is a severe progressive and debilitating disease with no approved treatment," John Vissing, principal investigator of the trial and director of the Copenhagen Neuromuscular Center at the National Hospital, Rigshospitalet, in Copenhagen, the site the first patient was dosed at, added to the statement.1 "This experimental treatment represents a new hope for the patients. It is a great motivation to know that the work we are doing here has the potential to make a life-changing difference."

1. Atamyo Therapeutics announces first patient dosed with ATA-100 gene therapy in LGMD-R9 clinical trial. News Release. Atamyo Therapeutics. September 26, 2022. 
2. Atamyo Therapeutics reaches significant regulatory and financial milestones for ATA-100, its gene therapy to treat limb-girdle muscular dystrophy type 2I/R9. News Release. Atamyo Therapeutics. February 24, 2022. 

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