Since its inception, life sciences company Solid Biosciences Inc. has been working to develop treatment options for patients with Duchenne muscular dystrophy (DMD). According to a recent press release, the company’s gene therapy candidate SGT-001 shows promise following functional, biomarker, safety, and efficacy data, alongside patient-reported outcomes. Thus far, the Phase 1/2 IGNITE DMD clinical trial has sourced data from 6 enrolled patients.

SGT-001

To begin, what is SGT-001? This novel adeno-associated viral (AAV) vector-mediate gene transfer therapy seeks to address DMD gene mutations. According to Gene Therapy Net:

Adeno-associated viruses, from the parvovirus family, are small viruses with a genome of single stranded DNA. These viruses can insert genetic material at a specific site…with near 100% certainty.

AAV vectors also have certain benefits, such as not prompting an immune response to the virus itself. In this case, SGT-001 delivers a synthetic DMD gene (“microdystrophin”) to patients, which helps create a functional protein that stabilizes muscles and prevents DMD progression. In prior studies, SGT-001 slowed or stopped DMD progression. One interesting aspect about SGT-001 is that it works regardless of where patients are in the disease process or what specific gene mutation they have. The treatment received Rare Pediatric, Fast Track, and Orphan Drug designations in the U.S., and Orphan Drug status in the EU.

IGNITE DMD Clinical Trial

Currently, available data from the IGNITE DMD trial was collected within 12-24 months (1-2 years) following treatment. Of the six patients, three received 5E13 vg/kg SGT-001 and three received 2E14 vg/kg SGT-001. Patients were between 5-14 years old at the time of the study. Findings included:

• While patients initially experienced some serious adverse reactions, they have all resolved without issue. Further, any additional reactions were mild to medium, and have also resolved. Thus, SGT-001 seems to be relatively safe and well-tolerated.
• Compared to natural history studies, SGT-001 data highlights a significant benefit in treated patients vs. untreated patients. Untreated patients saw North Star Ambulatory Assessment (NSAA) score declines in the same period of time that treated patients saw score increases.
  • Note: The NSAA is described as: “a 17-item rating scale that is used to measure functional motor abilities in ambulant children with Duchenne Muscular Dystrophy (DMD). It is usually used to monitor the progression of the disease and treatment effects.”
• Patients receiving SGT-001 were able to walk farther and improve their abilities over a 1-year period. Contrastingly, untreated patients declined 8.5m from baseline within the same period.
• SGT-001 improved pulmonary function in patients with DMD.
• Following treatment, patients receiving 2E14 vg/kg SGT-001 stabilized creatine kinase (CK). In the same group, a single dose of SGT-001 strengthened skeletal muscles using microdystrophin.
• Patients and caregivers reported better walking, standing, and recreational abilities. Additionally, patients experienced more mobility and less fatigue.

During the MDA Virtual Clinical & Scientific Conference, researchers from Solid Biosciences will present data from the IGNITE DMD clinical trial. Interested in seeing the presentation or listening to the webcast that Solid Biosciences shared? Click here.

Duchenne Muscular Dystrophy (DMD)

Duchenne muscular dystrophy (DMD) is a rare genetic disorder and one of 9 forms of muscular dystrophy. DMD gene mutations cause DMD. Normally, DMD encodes for the production of dystrophin, a protein that helps to strengthen muscle fiber. Additionally, dystrophin protects muscles from injury. But DMD mutations prevent the formation of dystrophin, leading to muscle weakness. Because DMD is inherited in an X-linked recessive pattern, it is extremely rare for the condition to be found in females. For example, 1 in every 3500 male births experiences DMD as opposed to 1 in 50 million female births. Symptoms usually appear before 6 years old. These include:

• Fatigue
• Toe-walking or a waddling gait
• Frequent tripping and/or falling
• Progressive muscle weakness that begins in the legs, pelvis, and thighs
• Enlarged calf muscles
• Difficulty walking or changing positions
• Scoliosis
• Joint contractures
• Cognitive impairment
• Cardiomyopathy (heart enlargement)

As muscles progressively weaken, patients may experience heart disease or respiratory failure.