LION-CS101, the study evaluating gene therapy AB-1003, is currently recruiting patients aged 18 years through 65 years with LGMD2I/R9 who have a confirmed mutation in FKRP.
The first patient has been dosed in the phase 1/2 LION-CS101 clinical trial (NCT05230459) evaluating Asklepios BioPharmaceutical (AskBio)’s AB-1003 (LION-101), an investigational adeno-associated virus (AAV) vector-based gene therapy intended to treat limb-girdle muscular dystrophy type 2I/R9 (LGMD2I/R9).1
AB-1003, which is delivered as a single dose via intravenous infusion, is intended to provide a functional copy of FKRP, the disease-targeted gene. Initiated in the second quarter of 2023, LION-CS101 is currently recruiting patients aged 18 years through 65 years with LGMD2I/R9 who have a confirmed mutation in FKRP. Participants in the double-blind, randomized, placebo-controlled, dose-escalation study will receive treatment with either AB-1003 at 1 of 2 dose levels or a placebo, depending on their assigned cohort. LION-CS101 is anticipated to enroll 14 patients in total.
“Hearing that the first patient has been dosed in this study evaluating AB-1003 is an exciting moment for the LGMD community and individuals living with this debilitating disease,” Kelly Brazzo, the cofounder and CEO of CureLGMD2i said in a statement.1 “Given the current lack of disease modifying treatments for LGMD, many in the community know of the potential of gene therapy. The initiation of this trial offers hope that patients with this condition may, in the future, have a significantly improved quality of life.”
Earlier this year, in March, AB-1003 received orphan drug designation from the European Commission through AskBio’s Europe-based subsidiary, BrainVectis.2 Prior to that, the gene therapy had been granted fast track designation by the FDA in June 2021.3 AskBio originally received clearance of its investigational new drug application for AB-1003 in May 2021.4
“While the inherited nature of LGMD 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,” Nicholas Johnson, MD, the principal investigator and vice chair of research in the Department of Neurology at Virginia Commonwealth University School of Medicine, added to the statement.1 “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.”
In addition to AB-1003, AskBio is also developing gene therapies for indications including Pompe disease (NCT03533673), Parkinson disease (NCT04167540), multiple system atrophy (NCT04680065), and congestive heart failure (NCT04179643), all of which have entered clinical development. Furthermore, in August 2022, AskBio announced that BrainVectis had received approval from France’s National Agency for Safety of Medicines and Health Products to begin recruiting patients for a phase 1/2 clinical trial of its AAV gene therapy for the treatment of early-stage Huntington disease, BV-101.5
“Unlike other attempts to treat Huntington’s Disease, BV-101 aims to restore cholesterol metabolism, reduce mutant huntingtin and to improve neuronal function,” Nathalie Cartier-Lacave, MD the founder of BrainVectis and vice president, Sector Lead Neurobiology, AskBio, said in an August 2022 statement.5 “Importantly, BV-101 does not affect the levels of normal huntingtin protein in cells. If this proves successful, we have the potential to change the course of a devastating disease that causes severe functional and cognitive decline.”