New Medicines

Type 2E limb girdle muscular dystrophy (LGMD2E)


New molecular entity
Sarepta Therapeutics
Sarepta Therapeutics

Development and Regulatory status

Phase II Clinical Trials
Feb 21Sarepta is seeking FDA confirmation to initiate a pivotal trial for SRP-9003 in 2021 [5].
Feb 19Sarepta has exercised its option to acquire Myonexus Therapeutics, a clinical-stage biotechnology company developing transformative gene therapies for five LGMDs: LGMD2E, LGMD2D, LGMD2B, LGMD2C and LGMD2L [4].
May 18FDA grants rare paediatric disease designation for the treatment of LGMD2E [3].
Feb 18Granted orphan drug status in US [3].


An in vivo adeno-associated virus serotype AAV-Rh74 vectored gene therapy, that encodes the human β-sarcoglycan gene. AAV-Rh74 vector facilitates systematic deliverance to skeletal, diaphragm and cardiac muscles without crossing the blood brain barrier.
A subtype of autosomal recessive limb girdle muscular dystrophy characterized by a childhood to adolescent onset of progressive pelvic- and shoulder-girdle muscle weakness, particularly affecting the pelvic girdle (adductors and flexors of hip). Prevalence is 1-9 per million [1]. In LGMD type 2E, disease usually occurs before age 10, progresses to loss of ambulation in the teen years, and often leads to death before age 30. There is currently no treatment or cure for LGMD type 2E [3].
Type 2E limb girdle muscular dystrophy (LGMD2E)

Trial or other data

Jun 21PI/II study (NCT03652259) is now expected to complete collection of primary outcome data in Feb 25 [7].
Mar 21Sarepta shares new results from the ongoing PI/II study of SRP-9003. In the first look at expression data from biopsies taken two years after a single administration of SRP-9003, results found sustained protein expression in muscle tissue. Protein expression in muscle was sustained for two years following treatment in the low dose cohort, with mean beta-sarcoglycan expression of 54% at 24 months, compared to 36% at Day 60, as measured by western blot. Mean NSAD score improvement of 5.7 points from baseline was sustained through 24 months in low-dose cohort, and mean NSAD score improvement of 4.0 points from baseline at one year in high-dose cohort [6].
Mar 21Sarpeta Therapeutics presents follow-up data of two years after a single administration of SRP 9003 in cohort 1 (low-dose cohort) and one year after treatment in cohort 2 (high-dose cohort) at Muscular Dystrophy Association Annual Clinical and Scientific Conference (MDA-2021). Treatment with 5x10e13 vg/kg of bidridistrogene xeboparvovec in three evaluable patients in the first cohort showed improvements from baseline across all functional measures, including the North Star Assessment for Dysferlinopathy (NSAD), time to rise, four-stair climb, 100-m walk test and 10-metre walk test, at 18 months. The mean NSAD improvement from baseline was 3.0 at 6 months and 5.7 at 18 months. In cohort 2 patients who received dose of 2x10e14vg/kg, all three patients demonstrated improvements from baseline across all functional measures, including the NSAD, time-to-rise, four-stair climb, 100-metre walk test and 10-meter walk test at 6 months. The mean NSAD improvement from baseline was 3.7 [3].
Oct 20PI/II study (NCT3652259) is active but no longer enrolling [2].
Oct 19Sarepta Therapeutics releases positive functional and safety results from the PI/II study (NCT03652259). Based on the safety profile, the company intends to test one higher dose of bidridistrogene xeboparvovec [3].
Apr 19Sarepta Therapeutics releases positive safety data from the trial and earlier efficacy and pharmacodynamic data in February [3].
Oct 18PI/II trial to assess the safety of bidridistrogene xeboparvovec (SRP-9003) in LGMD2E (Beta-sarcoglycan deficiency) patients starts (IRB17-00253; NCT03652259; SRP-9003-101). This first-in-human, single-center, open label, gene delivery study will enrol six children aged 4 to 15 years in the US only. Patients will receive a single IV infusion of SRP-9003. Primary outcome is safety; secondary outcomes include change From Baseline in Quantity of Beta-Sarcoglycan (B-SG) Protein Expression at week 8. Collection of these data is due to complete Feb 23 [2].