Solid Reports Positive Data for SGT-003 Gene Therapy in Phase 1/2 Trial of Duchenne

Bo Cumbo

Newly reported 90-day findings from the phase 1/2 INSPIRE DUCHENNE trial (NCT06138639) showed that treatment with SGT-003 (Solid Biosciences), an investigational gene therapy, was safe and resulted in significant microdystrophin expression in boys with Duchenne muscular dystrophy (DMD). The study is still enrolling, with at least 10 total participants expected to be dosed by early in the second quarter of 2025, and approximately 20 total participants by the fourth quarter of this year.¹

Using a cutoff date of February 11, 2025, the new data comprised clinical and efficacy findings from the first 3 patients dosed in the study, as well as safety data from the first 6 patients in the study. The first 3 participants, at the time of dosing, are two 5-year-old boys and one 7-year-old boy, while the second group consisted of a 6-year-old boy and two 7-year-old boys. In the study, patients received a one-time administration of SGT-003 at a dose of 1E14vg/kg and were followed throughout.

Within the first group, a 90-day biopsy revealed an average microdystrophin expression of 110%, as measured by western blot. Using mass spectrometry, the average microdystrophin expression was 108%, with patient 2 demonstrating the highest percentage (152%) and patient 3 showing the lowest (53%). In addition, those in the trial showed average dystrophin positive fibers of 78% and average beta sarcoglycan positive fibers of 70%.

SGT-003, which uses Solid’s proprietary AAV-SLB101 capsid to deliver an encoded microdystrophin protein containing the R16 and R17 nNos binding protein domains, was granted rare pediatric disease designation in May 2024. At the time, Bo Cumbo, president and chief executive officer at Solid, said in a statement that, "The key components of SGT-003 were rationally designed to improve on first generation gene therapies to provide skeletal muscle tropism, enhanced durability, and improved clinical outcomes."²

On markers of muscle injury and stress, treatment with the gene therapy resulted in a 57% decrease in serum creatine kinase (CK), a 45% decrease in serum asparate aminotransferase (AST), and a 54% decrease in serum alanine transaminase. Furthermore, these patients also demonstrated a 60% reduction in serum lactate dehydrogenase.

Additional findings showed a 42% reduction in serum titin, a marker of muscle breakdown, and a 59% decrease in embryonic myosin heavy chain positive fibers, a marker of dystrophin regeneration. Among 2 patients who had data at 180 days, investigators observed a mean cardiac function increase of 8% from baseline as measured by left ventricular ejection fraction. The company observed a 36% reduction in serum cardiac hs-troponin I (hs-cTnI) at Day 90 in one participant with elevated baseline levels, while two participants (N = 6) had elevated troponin at baseline, which decreased below initial values post-dose. Additionally, two of the first three participants had normal baseline cTnI levels.

READ MORE: Rituximab Shows No Effect Over Placebo in Preventing CIDP Disease Deterioration

In terms of safety, the most common adverse events (AEs) were nausea and vomiting, transient thrombocytopenia, infusion related hypersensitivity reaction, and fever, which were all consistent with AAV gene therapy. In the trial, no serious AEs, suspected unexpected serious adverse reactions, or evidence of thrombotic microangiopathy, atypical hemolytic uremic syndrome, hemolysis, or hepatic transaminitis (including elevated gamma-glutamyl transferase levels) were observed.

All treatment-related AEs resolved with no sequelae and none of the AEs that were observed required the use of additional immunomodulatory agents such as eculizumab, sirolimus, or rituximab. Of note, there was 1 AE of special interest, a mild, transient hs-troponin I elevation considered grade 1 that resolved without intervention. Furthermore, there was no evidence of myocarditis and no EKG or echocardiographic changes observed in such participant.

In 2022, Solid Biosciences paused development of SGT-001, its previous lead candidate for Duchenne muscular dystrophy (DMD), in favor of SGT-003. Prior to this shift, positive 2-year data from the Phase 1/2 IGNITE-DMD trial (NCT03368742) were presented at the 2022 MDA Clinical and Scientific Conference.^3,4

These results, based on the first three patients in the high-dose cohort (2E14 vg/kg), demonstrated improvements in motor function, including a mean 16-meter increase in the 6-Minute Walk Test (range, -12 to 39; +100.6 vs. natural history) and a -1.7 change in the North Star Ambulatory Assessment (range, -3 to -1; +4.3 vs. natural history). Pulmonary function also improved, with a mean 9.2% increase in forced vital capacity (range, -1.4 to 29.0; +19.2 vs. natural history) and a 6.5% improvement in peak expiratory flow (range, -5.8 to 14.8; +16.5 vs. natural history). Patient-reported outcomes also showed positive trends, and the therapy was well-tolerated.

REFERENCES
1. Initial Clinical Data from INSPIRE DUCHENNE Trial of SGT-003. News release. Solid Biosciences. February 18, 2025. Accessed February 18, 2025. https://www.sec.gov/Archives/edgar/data/1707502/000119312525028123/d913726d8k.htm
2. Solid Biosciences Receives Rare Pediatric Disease Designation from the FDA for Duchenne Muscular Dystrophy Gene Therapy Candidate SGT-003. News Release. Published April 1, 2024. Accessed February 18, 2025. https://investors.solidbio.com/news-releases/news-release-details/solid-biosciences-receives-rare-pediatric-disease-designation
3. Solid Biosciences provides second quarter 2022 business update and financial results. News release. Solid Biosciences. August 11, 2022. Accessed February 18, 2025. https://www.solidbio.com/about/media/press-releases/solid-biosciences-provides-second-quarter-2022-business-update-and-financial-results
4. Dreghici R, Redican S, Lawrence J, et al. Ignite DMD phase I/II study of SGT-001 microdystrophin gene therapy for DMD: 2-year outcomes update. Presented at MDA Clinical and Scientific Conference; March 13-16. Poster 46.