Patient Dosing Commenced in Phase 1/2 Gene Therapy Trial of Limb-Girdle Muscular Dystrophy Type 2I/R9


The trial is expected to include 14 individuals with genetically confirmed limb-girdle muscular dystrophy who will be randomly assigned 1:1 to either AB-1003 or placebo for a year-long treatment period.

Nicholas Johnson, MD, vice chair of research at the Department of Neurology, Virginia Commonwealth University School of Medicine

Nicholas Johnson, MD

According to a recent announcement, the first patient has been dosed in the phase 1/2 LION-CS101 clinical trial (NCT05230459) assessing AskBio’s investigational gene therapy AB-1003 for the treatment of limb-girdle muscular dystrophy type 2I/R9 (LGMD2I/R9). Recruitment for the trial remains ongoing.1

LGMD2I/R9, caused by mutations in the FKRP gene, is a form of LGMD that is characterized by weakness and wasting of the muscles in the arms and legs. AB-1003, also known as LION-101, uses an engineered viral vector—an adeno-associated virus (AAV)—to deliver a non-mutated version of the FKRP gene, by a single intravenous infusion. LGMD2I/R9 is a rare disease, estimated to affect more than 5000 people in the US and EU.

"While the inherited nature of limb-girdle muscular dystrophy means those with the FKRP gene mutation can't produce a normal FKRP protein for physiological muscle function, AB-1003 is designed to introduce the normal FKRP gene into the muscle and express a normal protein, and it has shown promise in restoring normal FKRP protein function in muscle in preclinical studies performed in mouse models of LGMD,” principal investigator Nicholas Johnson, MD, vice chair of research at the Department of Neurology, Virginia Commonwealth University School of Medicine, said in a statement.1

He added, "This trial is the first step toward evaluating the safety of AB-1003 and assessing the potential that AB-1003 has to improve the lives of patients with this serious, inherited ultra rare condition."

READ MORE: FDA Clears NS-050/NCNP-03 for Phase 1/2 Trial of Duchenne Muscular Dystrophy

The phase 1/2 trial, double-blind, placebo-controlled, and dose-escalation in design, is expected to include 14 adults with genetically confirmed LGMD2I who are followed for a 52-week treatment period. Initiated midway through 2023, the trial’s main goal is safety, assessed through treatment-emergent adverse events (TEAEs), serious AEs, and dose limiting toxicity. Participants will be treated in sequential, dose-level cohorts with 2 arms of different doses and 1 placebo arm.

In addition to having a genetic diagnosis of LGMD2I/R9, patients coming into the trial must have the ability to ascend 4 stairs between 2.5 and 10 seconds, walk/run 10 meters in less than 30 seconds, and be able to understand and comply with all study procedures. Sexually active females of childbearing potential and female and male partners of those receiving the study drug must use a barrier method of contraception for the first 6 months after dosing. Those with significant cardiomyopathy as defined by echocardiogram, evidence of conduction defect, NYHA Class 3 or 4 heart failure, or MRI gadolinium enhancement evidence of clinically important myocardial fibrosis, will be excluded.

"The first limb-girdle muscular dystrophy 2I/R9 patient dosed in the LION-CS101 clinical trial is another example of AskBio's success in taking gene therapy candidates, such as AB-1003, from the bench into clinical development," Jude Samulski, PhD, co-founder and chief scientific officer at AskBio, said in a statement.1 "With our knowledge and expertise, we are working to harness the power of gene therapies as potential treatments for many of the world's most devastating diseases. Our investigational therapy for limb-girdle muscular dystrophy is one of these and an important part of our portfolio, which also includes clinical stage investigational therapies for congestive heart failure, Huntington's disease, multiple system atrophy, Parkinson's disease, and Pompe disease."

1. AskBio announces first patient dosed in phase 1/phase 2 trial of AB-1003 gene therapy for limb-girdle muscular dystrophy type 2I/R9 (LGMD2I/R9). News release. AskBio. August 3, 2023. Accessed August 4, 2023.

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