Breakthrough in Duchenne Gene Therapy

Solid Biosciences has announced promising early results from its Phase 1/2 INSPIRE DUCHENNE trial (NCT06138639) evaluating SGT-003, an investigational gene therapy for Duchenne muscular dystrophy (DMD). The trial has shown significant expression of microdystrophin, an essential protein that could help slow disease progression and improve muscle function.

According to 90-day biopsy data from the first three participants—two five-year-old boys and one seven-year-old boy—SGT-003 achieved an average microdystrophin expression of 110% of normal levels as measured by Western blot analysis. Additional analysis using mass spectrometry showed an average expression of 108%, with one patient reaching 152% expression and another at 53%. This suggests a potential best-in-class therapy for DMD (NeurologyLive).

 

DMD: A Devastating Genetic Disorder

Duchenne muscular dystrophy (DMD) is a rare, progressive neuromuscular disorder caused by mutations in the dystrophin gene. It primarily affects young boys and leads to muscle degeneration, loss of ambulation, and eventual cardiac and respiratory failure (FDA).

While current treatments such as corticosteroids help manage symptoms, there is a significant need for disease-modifying therapies that address the underlying genetic cause of DMD (CHOP).

 

SGT-003: A Next-Generation Gene Therapy

SGT-003 is an adeno-associated virus (AAV)-based gene therapy designed to deliver microdystrophin directly to muscle cells. Unlike earlier-generation gene therapies, SGT-003 features Solid Biosciences' proprietary AAV-SLB101 capsid, which enhances delivery to skeletal and cardiac muscles while minimizing liver exposure (Solid Biosciences).

Key Findings from the Trial

• Microdystrophin Expression:

  • 110% average expression (Western blot)
  • 108% average expression (Mass spectrometry)
  • 78% dystrophin-positive fibers detected
  • 70% beta sarcoglycan-positive fibers (Clinical Trials Arena)

• Reduction in Muscle Damage Biomarkers:
  • 57% decrease in serum creatine kinase (CK)
  • 45% decrease in aspartate aminotransferase (AST)
  • 54% decrease in alanine transaminase (ALT)
  • 60% decrease in lactate dehydrogenase (LDH)
  • 42% reduction in serum titin, a marker of muscle breakdown
  • 59% decrease in embryonic myosin heavy chain-positive fibers, a marker of dystrophic regeneration (NeurologyLive)

• Early Indications of Cardiac Benefits:

  • Mean cardiac function increased by 8% from baseline in two participants
  • 36% reduction in cardiac hs-troponin I (hs-cTnI) at Day 90 in a participant with elevated baseline levels
  • No evidence of myocarditis or echocardiographic abnormalities (Solid Biosciences)

 

Safety Profile and Tolerability

SGT-003 was well-tolerated among the first six patients dosed, with no serious adverse events (SAEs). Reported adverse events (AEs) were mild to moderate and resolved without complications, including:

• Transient nausea and vomiting
• Fever
• Mild infusion-related hypersensitivity reaction
• Temporary decrease in platelet counts

Importantly, none of the participants required additional immunomodulatory therapy, such as eculizumab, sirolimus, or rituximab, to manage side effects (NeurologyLive).

 

Regulatory Plans and Expansion

With encouraging early results, Solid Biosciences plans to meet with the U.S. Food and Drug Administration (FDA) in mid-2025 to discuss the possibility of an accelerated approval pathway for SGT-003. The company expects to dose at least 10 patients by early Q2 2025 and up to 20 participants by Q4 2025 (Solid Biosciences).

 

Market Reaction: Stock Soars Over 78%

Following the announcement of the 90-day biopsy data, Solid Biosciences' stock surged by 78.66%, jumping from $4.03 (14 February close) to $7.20 on 18 February after markets opened (Clinical Trials Arena).

This surge highlights investor confidence in SGT-003 as a potential game-changer in the DMD treatment landscape.

 

What’s Next?

Further Trials & Long-Term Data

• Continued long-term monitoring of current participants
• Expansion of the INSPIRE DUCHENNE trial
• Additional biomarker and functional assessments over a 180-day period
• Potential regulatory filings for accelerated approval

 

DMD Gene Therapy Landscape

While SGT-003 shows exciting potential, other companies are also exploring gene therapy options for DMD:

• Cumberland Pharmaceuticals reported positive Phase II results for ifetroban as a potential DMD treatment.
• Entrada Therapeutics has received MHRA authorization in the UK to start its two-part Phase I/II trial, ELEVATE-44-201 (Clinical Trials Arena).

 

Conclusion: A Game-Changer for DMD?

The early clinical data from Solid Biosciences' SGT-003 gene therapy offer hope for the DMD community. With strong efficacy signals, biomarker improvements, and a favorable safety profile, SGT-003 is emerging as a leading candidate in the race for gene therapy solutions for DMD.

As Solid Biosciences prepares for regulatory discussions and trial expansion, the DMD community, investors, and medical professionals eagerly await further data to confirm whether SGT-003 can truly transform the treatment landscape for Duchenne muscular dystrophy.

 

Sources & References:

• Solid Biosciences Reports Positive Initial Data
• NeurologyLive: SGT-003 Gene Therapy Phase 1/2 Trial
• Clinical Trials Arena Report
• FDA DMD Gene Therapy Approval