RGX-202 Shows Continued Promise in DMD, AJ201 Meets End Points in Spinal and Bulbar Muscular Atrophy, Ponesimod Effect Sustained Over Long-Term

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Welcome to this special edition of Neurology News Network. I'm Marco Meglio.

Newly announced data from level 2 the phase 1/2 AFFINITY DUCHENNE trial (NCT05693142) showed that treatment with higher doses of RGX-202 (REGENXBIO), an investigational gene therapy, led to positive changes in disease trajectory and improvements in certain biomarkers among patients with Duchenne muscular dystrophy (DMD). Relative to natural history cohorts, those on the gene therapy showed improvements across a variety of scales, including North Star Ambulatory Assessment (NSAA) and timed function tests (Time to Stand, 10 Meter Walk-run, Time to Climb). At 9 months, RGX-202-treated patients demonstrated an average improvement of 4 points on NSAA relative to baseline and a 4.8-point difference compared with natural history cohorts. Notably, dose level 2 participants’ timed task velocity changes exceeded minimal clinically important difference (MCID) benchmarks at 12 months.

Recently announced data from a phase 1/2 trial (NCT05517603) showed that investigational AJ201 (AnnJi Pharmaceuticals) was safe and led to meaningful treatment-related improvements in efficacy and exploratory measures among patients with spinal and bulbar muscular atrophy (SBMA). Coupled with positive changes in functional, biochemical, and molecular markers, the findings further support the development of AJ201 as a treatment for SBMA. The study, a randomized, double-blind clinical trial lasting approximately 12 weeks, featured 24 patients with SBMA who were randomly assigned to AJ201 at 600 mg/day or placebo. Although the study was not powered for efficacy, the drug did show encouraging signals on several clinical end points. Overall, treatment with the novel compound led to a clinically meaningful 17.6-meter gain in the 6-Minute Walk Test and a 0.8-point increase in the SBMA Functional Rating Scale (SBMAFRS) on average.

Newly reported data from the phase 3 OPTIMUM-LT open-label extension trial (NCT03232073) showed that treatment with ponesimod (Ponvory; Vanda Pharmaceuticals) was safe and led to sustained reduction in relapses, MRI lesions, and low disability accumulation among patients with relapsing multiple sclerosis over a long-term period. At time points of up to 8.2 years, more than half of the patients included were still relapse-free. The extension trial featured 877 patients from the original OPTIMUM phase 3 study, the trial that led to ponesimod’s FDA approval in 2021. Of the 439 patients receiving ponesimod in both the core and extension trial, 352 completed. Within this group, results showed an annualized relapse rate of 0.143 (95% CI, 0.123-0.167), with 56.7% of patients relapse-free over the combined analysis period, which lasted up to 8.2 years. Overall, the median time to relapse for the approved sphingosine-1-phosphate receptor (S1P) modulator was 402.71 weeks.

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