Positive initial data reported for SGT-003 to treat Duchenne muscular dystrophy
90-day interim biopsy data in the first 3 patients revealed an average microdystrophin expression of 110% and improvements in muscle health and resilience biomarkers.
Positive initial data reported for SGT-003 to treat Duchenne muscular dystrophy | Image Credit: © luchschenF - © luchschenF - stock.adobe.com.
Positive initial data has been reported by Solid Biosciences Inc. for SGT-003, a Duchenne muscular dystrophy (DMD) gene therapy candidate.1
Results from the phase 1/2 INSPIRE DUCHENNE trial in the first 3 patients dosed revealed an average microdystrophin expression of 110%, as measured by western blot, and improvements in multiple biomarkers that are indicators of muscle health and resilience, according to the company's announcement.
Among the first 6 patients dosed as of the February 11, 2025 cutoff date, all 6 have reached at least 20 days post SGT-003 treatment, with the gene therapy being well tolerated, according to Solid. Adverse events (AEs) were typical of those observed in AAV gene therapy, such as nausea, vomiting, fever, and transient declines in platelets in some participants.
There were no serious AEs or suspected unexpected serious adverse reactions. Additionally, no AEs that were observed required the use of additional immunomodulatory agents such as eculizumab, sirolimus or rituximab.
In INSPIRE DUCHENNE—a first in human, open-label, single-dose, multicenter trial evaluating safety, tolerability, and efficacy of SGT-003—a dose of 1E14vg/kg is administered as a one-time infusion. The trial remains ongoing, with at least 10 total participants expected to be dosed by the second quarter of 2025.
The first trio of participants dosed in the phase 1/2 trial are two 5-year-old boys and a 7-year-old boy at the time of dosing. The second three participants are a 6-year-old boy and two 7-year-old boys at the time of dosing.
Among the interim data at day 90 for the first 3 boys dosed, mean microdystrophin expression percent normal (Western Blot) was 110%. Mean microdystrophin expression percent normal (Mass Spectrometry) among these 3 patients was 108%.
According to results, muscle integrity biomarker evaluation at day 90 among the first 3 patients included mean reductions observed in markers of muscle injury and stress included:
- Serum creatine kinase (CK) (IU/L): -57%
- Serum aspartate aminotransferase (AST) (IU/L): -45%
- Serum alanine transaminase (ALT) (IU/L): -54%
- Serum lactate dehydrogenase (LDH) (IU/L): -60%
Mean reductions observed in markers of muscle breakdown and dystrophic regeneration included:
- Serum titin (pmol/L): -42%
- Embryonic myosin heavy chain (eMHC) positive fibers: -59%
Measure of potential cardiac benefit included:
- At Day 180, mean cardiac function increased by 8% (N=2) from baseline as measured by left ventricular ejection fraction
- The third participant had not reached Day 180 follow up as of the data cutoff date of February 11, 2025
Reduction in serum cardiac hs-troponin I (hs-cTnI) of -36% observed at Day 90 in one participant who entered the trial with elevated hs-cTnI levels:
- Two of the first three participants entered the study with normal baseline cTnI levels
- Two participants in total (n = 6) had elevated troponin at baseline that reduced below initial baseline values post-dose
On April 1, 2024, SGT-003 was granted rare pediatric disease designation from the FDA.2
References:
1. Solid Biosciences Reports Positive Initial Clinical Data from Next-Generation Duchenne Gene Therapy Candidate SGT-003. Solid Biosciences. Press release. February 18, 2025. Accessed February 18, 2025. https://investors.solidbio.com/news-releases/news-release-details/solid-biosciences-reports-positive-initial-clinical-data-next
2. Fitch, J. DMD candidate SGT-003 receives Rare Pediatric Disease Designation. Contemporary Pediatrics. April 2, 2024. Accessed February 18, 2025. https://www.contemporarypediatrics.com/view/dmd-candidate-sgt-003-receives-rare-pediatric-disease-designation
