Gene therapy improves functional outcomes for boys with Duchenne muscular dystrophy

Key takeaways:

• RGX-202 was safe and well-tolerated in all 12 patients at two different doses with no serious adverse events.
• The treatment led to timed function test improvements vs. a natural history cohort.

SAN DIEGO — Two dose levels of a single-administration gene therapy were well-tolerated and led to functional improvements in ambulatory boys with Duchenne muscular dystrophy, interim data show.

“Several microdystrophin gene therapy programs are approved for Duchenne [muscular dystrophy] and are slightly different when it comes to using [adeno-associated virus (AAV)] serotypes and different promoters,” Aravindhan Veerapandiyan, MD, neurologist at Arkansas Children’s Hospital, said during a late-breaking research session at the American Academy of Neurology Annual Meeting.

Veerapandiyan and colleagues examined interim safety, efficacy and tolerability results for RGX-202, an investigational, single-administration IV microdystrophin-expressed, AAV gene therapy in a cohort of ambulatory boys in a phase 1/2 clinical trial.

Their 12-month study included 12 boys aged 1 to younger than 12 years, able to walk unassisted, with a genetically confirmed Duchenne muscular dystrophy (DMD) diagnosis and no evidence of antibodies prior to gene therapy administration.

At baseline, all participants underwent therapeutic administration, muscle biopsy and muscle function evaluation. Skeletal and cardiac MRI were performed in participants aged 4 years and older.

Following administration, muscle biopsy and muscle function assessment occurred at 3 months, with subsequent muscle function assessments scheduled for 6, 9 and 12 month intervals.

Dose levels varied among the patient population; two patients aged 1 to 3 years and seven patients aged 4 to 11 years received dose level two, of 2×10^14 genome copies (GC)/kg body weight, while three patients aged 4 to 11 years received dose level one, of 1×10^14 GC/kg.

While the evaluation period for RGX-202 is 12 months, during which safety will be continuously monitored, follow-up is expected to last up to 5 years.

According to interim results, no serious adverse events or serious adverse events of interest were recorded for any age group at either dose for all 12 DMD patients. The only adverse events reported were nausea, vomiting and fatigue, which eventually resolved.

The researchers also reported treatment with RGX-202 led to improvements via mean change in the North Star Ambulatory Assessment as well as timed function tests compared with a natural history cohort at 9 months at dose level two and at 12 months at dose level one.

Data further showed that RGX-202 had significant microdystrophin expression at dose level one in patients aged 4 to 7 years, as well as dose level two in patients aged 1 to 3 years and aged 4 to 7 years.

“Biomarkers support consistent, robust expression, transduction and localization of dystrophin,” Veerapandiyan noted, “And we have plans to proceed with the study at dose level two.”