bidridistrogene xeboparvovec (SRP-9003) / Sarepta Therap - LARVOL DELTA

Pharmacokinetic and Pharmacodynamic Evaluation of Bidridistrogene Xeboparvovec in an Aged Murine Model of Limb-Girdle Muscular Dystrophy Type 2E/R4. (PubMed, Hum Gene Ther) - P1, P1/2, P3 | "Overall, a dose-dependent increase in vector exposure across tissue types was observed, with a nonlinear, exposure-dependent increase in both SGCB expression and functional improvement that reached saturation at 7.4 × 1013 vg/kg. Pharmacokinetic and pharmacodynamic analyses demonstrated a robust relationship between vector biodistribution, SGCB expression, and muscle force, further supporting clinical development of bidridistrogene xeboparvovec at the highest dose (7.4 × 1013 vg/kg), across a broad LGMD2E/R4 population and regardless of disease progression."

Journal • PK/PD data • Preclinical • Fibrosis • Gene Therapies • Immunology • Muscular Dystrophy

Gene Delivery Clinical Trial of SRP-9003 (Bidridistrogene Xeboparvovec) for Participants With Limb-Girdle Muscular Dystrophy, Type 2E (LGMD2E) (Beta-Sarcoglycan Deficiency) (clinicaltrials.gov) - P1/2 | N=6 | Terminated | Sponsor: Sarepta Therapeutics, Inc. | Trial completion date: Feb 2027 ➔ Jan 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Feb 2027 ➔ Jan 2025; Study is being terminated due to a business decision.

Trial completion date • Trial primary completion date • Trial termination • Muscular Dystrophy

U.S. FDA Grants Platform Technology Designation to the Viral Vector Used in SRP-9003, Sarepta’s Investigational Gene Therapy for the Treatment of Limb Girdle Muscular Dystrophy Type 2E/R4 (Businesswire) - "Sarepta Therapeutics, Inc...announced that the rAAVrh74 viral vector used in the investigational gene therapy SRP-9003 (bidridistrogene xeboparvovec) for the treatment of limb-girdle muscular dystrophy type 2E/R4, has been granted platform technology designation by the U.S. Food & Drug Administration."

FDA event • Muscular Dystrophy

In Situ Biodistribution and Localization of Bidridistrogene Xeboparvovec (SRP-9003) in LGMD2E/R4 Mice After 1 Year of Follow-up (ASGCT 2025) - "This study demonstrates the applicability of RNAscope™ to determine spatial, cellular organization, and molecular trafficking of SRP-9003. The results indicate the durability of SRP-9003 to generate stable SGCB mRNA and protein expression over extended periods of up to 1 year in a mouse model of LGMD2E/R4. These data may be useful to inform future application of RNAscope™ for biodistribution evaluation of AAVrh74 gene therapy."

Preclinical • Gene Therapies • Muscular Dystrophy

EMERGENE: A Trial to Learn More About an Experimental Gene Therapy Called Bidridistrogene Xeboparvovec (SRP-9003) as a Possible Treatment for Limb Girdle Muscular Dystrophy 2E/R4 (clinicaltrials.gov) - P3 | N=17 | Active, not recruiting | Sponsor: Sarepta Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Gene Therapies • Muscular Dystrophy

In Situ Biodistribution and Localization of Bidridistrogene Xeboparvovec (SRP-9003) in LGMD2E/R4 (New Directions 2024) - No abstract available

In Situ Biodistribution and Localization of Bidridistrogene Xeboparvovec (SRP-9003) in LGMD2E/R4 Mice (ASGCT 2024) - "Proof of principle for in-situ detection of bidridistrogene xeboparvovec was established following IM evaluation. Vector genome copies were detected in all bidridistrogene xeboparvovec-dosed animal tissues by both RNAscope™ and ddPCR 24 hours after injection with DNA levels decreasing at day 7. In contrast hSCGB mRNA transcript levels plateaued at day 14 using both RNAscope™ and RT-ddPCR."

Preclinical • Gene Therapies • Muscular Dystrophy

A Trial to Learn More About an Experimental Gene Therapy Called Bidridistrogene Xeboparvovec (SRP-9003) as a Possible Treatment for Limb Girdle Muscular Dystrophy 2E/R4 (EMERGENE) (clinicaltrials.gov) - P3 | N=15 | Recruiting | Sponsor: Sarepta Therapeutics, Inc.

Gene therapy • New P3 trial • Gene Therapies • Muscular Dystrophy

Gene Delivery Clinical Trial of SRP-9003 (Bidridistrogene Xeboparvovec) for Participants With Limb-Girdle Muscular Dystrophy, Type 2E (LGMD2E) (Beta-Sarcoglycan Deficiency) (clinicaltrials.gov) - P1/2 | N=6 | Active, not recruiting | Sponsor: Sarepta Therapeutics, Inc. | Trial completion date: Feb 2025 ➔ Feb 2027 | Trial primary completion date: Feb 2025 ➔ Feb 2027

Trial completion date • Trial primary completion date • Muscular Dystrophy

A Gene Transfer Single Dose Study to Evaluate the Safety, Tolerability and Efficacy of SRP-9003 in Non-Ambulatory and Ambulatory Participants With Limb Girdle Muscular Dystrophy, Type 2E/R4 (Beta-Sarcoglycan [β-SG] Deficiency) (clinicaltrials.gov) - P1 | N=6 | Active, not recruiting | Sponsor: Sarepta Therapeutics, Inc. | Enrolling by invitation ➔ Active, not recruiting | Trial completion date: Jan 2027 ➔ Aug 2028 | Trial primary completion date: Jan 2026 ➔ Aug 2028

Enrollment closed • Trial completion date • Trial primary completion date • Gene Therapies • Muscular Dystrophy

A Gene Transfer Single Dose Study to Evaluate the Safety, Tolerability and Efficacy of SRP-9003 in Non-Ambulatory and Ambulatory Participants With Limb Girdle Muscular Dystrophy, Type 2E/R4 (Beta-Sarcoglycan [β-SG] Deficiency) (clinicaltrials.gov) - P1 | N=5 | Enrolling by invitation | Sponsor: Sarepta Therapeutics, Inc.

New P1 trial • Gene Therapies • Muscular Dystrophy

Safety, β-sarcoglycan expression, and functional outcomes from systemic gene transfer of bidridistrogene xeboparvovec in limb-girdle muscular dystrophy type 2E/R4 (WMS 2022) - P1/2 | "Post hoc analysis showed clinically important improvements in NSAD outcomes compared with an untreated natural history cohort (5.9-point difference at Y2; 95% CI, -1.5, 13.3). These data suggest sustained efficacy of SRP-9003 therapy, supporting advancement of the clinical development program."

Clinical • Gene Therapies • Muscular Dystrophy

Safety, β-Sarcoglycan Expression, and Functional Outcomes from Systemic Gene Transfer of rAAVrh74.MHCK7.hSGCB in LGMD2E/R4 (ASGCT 2022) - P1/2 | "These data suggest long-term efficacy of SRP-9003 therapy, supporting advancement of the clinical development program."

Clinical • Gene Therapies • Muscular Dystrophy

Safety, ß-Sarcoglycan Expression, and Functional Outcomes From Systemic Gene Transfer of rAAVrh74.MHCK7.hSGCB in LGMD2E/R4 (AAN 2022) - P1/2 | "These data suggest long-term efficacy of SRP-9003 therapy, supporting advancement of the clinical development program."

Clinical • Gene Therapies • Muscular Dystrophy

[VIRTUAL] Safety, Beta-Sarcoglycan Expression and Functional Outcomes From rAAVrh74. MHCK7.SGCB Systemic Gene Transfer in LGMD2E/R4 (EAN 2021) - P1/2 | "hSGCB construct (SRP-9003) designed to restore functional SGCB...All patients received prednisone 1mg/kg/day one day before treatment (tapering after 30–60 days)... These data suggest long-term efficacy of SRP- 9003 gene-transfer therapy, supporting advancement of the clinical development program."

Clinical • Gene Therapies • Immunology • Muscular Dystrophy

Gene Delivery Clinical Trial of SRP-9003 for Participants With Limb-Girdle Muscular Dystrophy, Type 2E (LGMD2E) (Beta-Sarcoglycan Deficiency) (clinicaltrials.gov) - P1/2; N=6; Active, not recruiting; Sponsor: Sarepta Therapeutics, Inc.; Trial completion date: Feb 2023 ➔ Feb 2025; Trial primary completion date: Feb 2023 ➔ Feb 2025

Clinical • Trial completion date • Trial primary completion date • Muscular Dystrophy

[VIRTUAL] Safety, β-Sarcoglycan Expression, and Functional Outcomes from Systemic Gene Transfer of rAAVrh74.MHCK7.SGCB in Limb Girdle Muscular Dystrophy Type 2E/R4 (ASGCT 2021) - P1/2 | "For all patients, prednisone 1 mg/kg/day was initiated 1 day before treatment (tapering after 30-60 days). These data suggest the long-term efficacy of SRP-9003 gene transfer therapy, supporting advancement of the clinical development program."

Clinical • Gene Therapies • Immunology • Muscular Dystrophy

[VIRTUAL] Safety, β-sarcoglycan Expression, and Functional Outcomes from Systemic Gene Transfer of rAAVrh74.MHCK7.SGCB in Limb Girdle Muscular Dystrophy Type 2E (MDA 2021) - P1/2 | "Here we report initial findings of a Phase 1/2 clinical gene transfer trial of rAAVrh74.MHCK7.hSGCB (SRP-9003) in patients with LGMD2E. In this first-in-human, single-center, open-label, systemic gene delivery, Phase 1/2 study (NCT03652259), 6 patients with LGMD2E received SRP-9003 in escalating doses...For all patients, prednisone 1 mg/kg/day was initiated 1 day before treatment (tapering after 30–60 days)... These data suggest the long-term efficacy of rAAVrh74.MHCK7.hSGCB gene transfer therapy, supporting advancement of the clinical development program."

Clinical • Gene Therapies • Immunology • Muscular Dystrophy

Gene Delivery Clinical Trial of SRP-9003 for Patients With LGMD2E (Beta-sarcoglycan Deficiency) (clinicaltrials.gov) - P1/2; N=6; Active, not recruiting; Sponsor: Sarepta Therapeutics, Inc.; Trial completion date: Dec 2020 ➔ Feb 2023; Trial primary completion date: Dec 2020 ➔ Feb 2023

Clinical • Trial completion date • Trial primary completion date • Muscular Dystrophy

Long-term functional data from Sarepta Therapeutics’ Most Advanced Gene Therapy Programs to be Presented at Upcoming Annual Congress of the World Muscle Society (GlobeNewswire) - "Sarepta...today announced that new data from its most advanced gene therapy programs will be presented at the WMS25 Virtual Congress, the 25th International Annual Congress of the World Muscle Society, being held Sept. 28 – Oct. 2....Sarepta will host a webcast and conference call on Monday, Sept. 28, 2020 at 8:30 a.m. ET, to discuss the results, which include two-year functional data from Study 101 of SRP-9001 for Duchenne muscular dystrophy and 18-month functional results from Cohort 1 in the study of SRP-9003 for Limb-girdle muscular dystrophy Type 2E."

Clinical data • P1/2 data • Preclinical • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy