Solid Biosciences Announces Positive Initial Data from Phase 1/2 INSPIRE DUCHENNE Trial for SGT-003, a Next-Generation Gene Therapy for Duchenne Muscular Dystrophy

CAMBRIDGE, Mass. — Solid Biosciences Inc. (Nasdaq: SLDB), a life sciences company developing precision genetic medicines for neuromuscular and cardiac diseases, today announced positive interim data from the ongoing Phase 1/2 INSPIRE DUCHENNE trial evaluating SGT-003, a next-generation AAV-based gene therapy candidate for the treatment of Duchenne muscular dystrophy (Duchenne). The data, as of the cutoff date of February 11, 2025, demonstrated robust microdystrophin expression, improvements in key biomarkers of muscle health, and a favorable safety profile in the first six participants dosed.

Key Highlights from the INSPIRE DUCHENNE Trial

• Microdystrophin Expression:
  • The first three participants showed an average microdystrophin expression of 110%, as measured by western blot, indicating strong transduction and protein production.
  • This level of expression is among the highest reported in Duchenne gene therapy trials to date, suggesting potential best-in-class efficacy.
• Biomarker Improvements:
  • Significant reductions in biomarkers of muscle damage and stress were observed, including:
• Serum creatine kinase (CK): -57%
• Aspartate aminotransferase (AST): -45%
• Alanine transaminase (ALT): -54%
• Lactate dehydrogenase (LDH): -60%
  • These reductions indicate improved muscle integrity and reduced muscle breakdown, which are critical for slowing disease progression.
• Early Cardiac Benefits:
  • Two participants showed an 8% improvement in left ventricular ejection fraction (LVEF) by Day 180, suggesting potential cardiac benefits.
  • One participant with elevated high-sensitivity troponin I (hs-cTnI) levels at baseline experienced a 36% reduction by Day 90, further supporting cardiac improvements.
• Safety Profile:
  • SGT-003 was well-tolerated in all six participants, with no serious adverse events (SAEs), suspected unexpected serious adverse reactions (SUSARs), or evidence of thrombotic microangiopathy (TMA) or atypical hemolytic uremic syndrome (aHUS).
  • Adverse events (AEs) were consistent with those observed in other AAV gene therapies, including nausea, vomiting, fever, and transient thrombocytopenia, all of which resolved without intervention.
  • No additional immunomodulatory agents (e.g., eculizumab, sirolimus, or rituximab) were required to manage AEs.

Trial Design and Progress

The INSPIRE DUCHENNE trial is a first-in-human, open-label, single-dose, multicenter study evaluating the safety, tolerability, and efficacy of SGT-003 at a dose of 1E14 vg/kg in pediatric patients with Duchenne.

• Enrollment Status:
  • As of February 11, 2025, six participants (ages 5–7 years) have been dosed, with at least 10 participants expected to be dosed by Q2 2025 and approximately 20 participants by Q4 2025.
  • The trial has six active clinical sites in the U.S. and Canada, with additional sites planned in the UK and Italy by the end of 2025.
• Regulatory Pathway:
  • Solid Biosciences plans to request a meeting with the FDA in mid-2025 to discuss the potential for an accelerated approval pathway for SGT-003, based on the robust biomarker and safety data.

SGT-003: A Differentiated Gene Therapy for Duchenne

SGT-003 is an investigational AAV-based gene therapy designed to address the root cause of Duchenne by delivering a microdystrophin transgene using Solid’s proprietary AAV-SLB101 capsid.

• Unique Features of SGT-003:
  • The microdystrophin construct includes the R16/17 domains, which localize neuronal nitric oxide synthase (nNOS) to the muscle, improving blood flow and reducing muscle fatigue.
  • The AAV-SLB101 capsid was rationally designed to enhance cardiac and skeletal muscle transduction while reducing liver targeting, as demonstrated in preclinical studies.
• Potential Best-in-Class Profile:
  • The combination of high microdystrophin expression, improvements in muscle and cardiac biomarkers, and a favorable safety profile positions SGT-003 as a potential best-in-class therapy for Duchenne.

Leadership and Investigator Perspectives

• Bo Cumbo, President and CEO of Solid Biosciences:
  • “We are thrilled with the initial data from the INSPIRE DUCHENNE trial, which demonstrate the potential of SGT-003 to be a transformative therapy for Duchenne. The robust microdystrophin expression and biomarker improvements, coupled with the favorable safety profile, underscore the promise of our differentiated approach. We look forward to engaging with regulators to discuss an accelerated approval pathway.”
• Craig McDonald, MD, UC Davis Health and INSPIRE DUCHENNE Investigator:
  • “The early results from SGT-003 are highly encouraging. The inclusion of the nNOS binding domain in the microdystrophin construct may play a critical role in improving clinical outcomes, and I am eager to see longer-term functional data.”
• Gabriel Brooks, MD, Chief Medical Officer at Solid Biosciences:
  • “These data highlight the importance of not just microdystrophin expression, but also the restoration and preservation of muscle health. The early cardiac benefits observed are particularly promising and suggest that SGT-003 could address both skeletal and cardiac aspects of Duchenne.”

About Duchenne Muscular Dystrophy

Duchenne is a rare, progressive, and fatal genetic disorder caused by mutations in the dystrophin gene, leading to muscle degeneration and weakness. It primarily affects boys, with symptoms appearing between 3–5 years of age. Approximately 1 in 3,500–5,000 male births are affected, with an estimated 5,000–15,000 cases in the U.S. alone.

About Solid Biosciences

Solid Biosciences is a precision genetic medicine company focused on developing AAV-based gene therapies for rare neuromuscular and cardiac diseases, including Duchenne, Friedreich’s ataxia (FA), and catecholaminergic polymorphic ventricular tachycardia (CPVT). The company’s proprietary AAV-SLB101 capsid and innovative genetic regulators aim to advance the field of gene therapy and improve outcomes for patients with devastating rare diseases.

Reference:
https://investors.solidbio.com/news-releases/news-release-details/solid-biosciences-reports-positive-initial-clinical-data-next

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