Limb-Girdle Muscular Dystrophy Gene Therapy Gets EC Orphan Drug Designation


AskBio’s AB-1003 was previously granted fast track designation by the FDA.

Asklepios BioPharmaceutical (AskBio)’s AB-1003 (LION-101), an investigational adeno-associated virus (AAV) vector-based gene therapy currently being evaluated for the treatment of limb-girdle muscular dystrophy type 2I/R9 (LGMD2I/R9) in a phase 1/2 clinical trial (NCT05230459), has received orphan drug designation from the European Commission (EC) through AskBio’s Europe-based subsidiary, BrainVectis.1

AB-1003 is delivered as a single dose via intravenous infusion. AB-1003 previously received clearance of its investigational new drug application from the FDA in May 2021.2 Soon after, in June 2021, AB-1003 was granted fast track designation by the FDA.3

"The EC orphan drug designation for AB-1003 is an important recognition of the unmet medical need in LGMD, which has no approved therapy," Sheila Mikhail, co-founder and chief executive officer, AskBio, said in a statement regarding the news.1 "The burden of this rare form of muscular dystrophy on patients and their families is significant, and this decision supports our efforts to potentially bring a new therapeutic option to people in the EU living with the 2I/R9 type of this devastating disease."

The multicenter, double-blind, randomized, placebo-controlled, dose-escalation clinical trial is expected to enroll 10 patients aged 18 to 65 years with LGMD2I/R9 and a confirmed mutation in the FKRP gene. Participants must have the ability to ascend 4 stairs within 2.5 to 10 seconds and the ability to walk or run 10 meters in less than 30 seconds. Patients with significant cardiomyopathy; evidence of conduction defect; NYHA class 3-4 heart failure; MRI gadolinium enhancement evidence of clinically important myocardial fibrosis; any contraindication to MRI; any implantation that would distort cardiac MRI images; hypersensitivity to contrast dyes, shellfish, or iodine; history of chronic liver disease or abnormal liver function; abnormal renal function; or a neutralizing antibody titer to AAV9 greater than 1:5 will be excluded from participation in the study. Additional exclusion criteria relate to patient health status and treatment history.

The trial will treat participants in 2 experimental cohorts at 2 different dose levels. A placebo comparator arm is also included in the study design. The primary end point is the occurrence of treatment emergent adverse events (AEs), serious AEs, and dose-limiting toxicities. The trial is estimated to be completed in December 2028.

Several other gene therapies for LGMD are also currently in development. Atamyo Therapeutics has therapies for 5 different LGMD subtypes in its pipeline.4 Notably, the company announced in September 2022 that the first patient was dosed in its clinical trial for ATA-100, which is intended to treat LGMD2I/R9.5 Meanwhile, Sarepta Therapeutics is developing treatments for 6 LGMD subtypes.6 Data from a phase 1/2 study for SRP-9003, an AAV vector-based gene therapy intended to treat LGMD type 2E, were presented at the 2021 Muscular Dystrophy Association (MDA) Annual Clinical and Scientific Conference. It was reported that patients treated with SRP-9003 showed improvements in assessments including time-to-rise, four-stair climb, 100-meter walk test, and 10-meter walk test.7

1. AskBio receives European Commission orphan drug designation through its EU-based subsidiary BrainVectis for AB-1003, a novel investigational AAV gene therapy for the treatment of limb-girdle muscular dystrophy (LGMD). News release. Asklepios BioPharmaceutical, Inc. February 16, 2023. Accessed March 2, 2023. 
2. AskBio announces IND for LION-101, a novel investigational AAV gene therapy for the treatment of Limb-Girdle muscular dystrophy type 2I/R9, cleared to proceed by US FDA. News release. Asklepios BioPharmaceutical. May 25, 2021. Accessed June 2, 2021. 
3. AskBio receives FDA fast track designation for LION-101, a novel investigational AAV gene therapy for the treatment of limb-girdle muscular dystrophy type 2I/R9 (LGMD2I/R9). News release. Asklepios BioPharmaceutical, Inc. June 28, 2021. Accessed March 2, 2023. 
4. Atamyo Therapeutics. Our pipeline. Website. Accessed March 3, 2023. 
5. Atamyo Therapeutics announces first patient dosed with ATA-100 gene therapy in LGMD-R9 clinical trial. News Release. Atamyo Therapeutics. September 26, 2022. 
6. Sarepta Therapeutics. Our pipeline. Website. Accessed March 3, 2023. 
7. Rodino-Klapac L. Safety, β-sarcoglycan Expression, and Functional Outcomes from Systemic Gene Transfer of rAAVrh74.MHCK7.SGCB in Limb-Girdle Muscular Dystrophy Type 2E. Presented at MDA Clinical and Scientific Conference 2021; March 15-18.
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