Lysogene Provides Updates and Topline Results from Phase 2/3 AAVance Gene Therapy Clinical Study

Regulatory News:

Lysogene (FR0013233475 – LYS) (Paris:LYS), a phase 3 gene therapy platform Company targeting central nervous system (CNS) diseases, today announced topline results from the Phase 2/3 AAVance study evaluating LYS-SAF302, an investigational gene therapy for the treatment of MPS IIIA. In subjects enrolled at <30 months of age (ancillary cohort, n=6), a statistically significant improvement in cognitive development compared to natural history (NH) was observed at 24 months post-dosing. Subjects in this cohort also achieved key secondary efficacy criteria. The statistical analysis confirms previously communicated qualitative observations in the younger patient population, with consistency of effect across the outcome measures.

The study did not meet its primary efficacy endpoint for the main cohort (12 subjects enrolled at ≥ 30 months of age) in demonstrating a statistically significant improvement in the cognitive DQ at 24 months post-dosing as assessed by the BSID-III, compared to the NH cohort. For this cohort, key secondary efficacy endpoints were not met, including percent of subjects with stabilized or improved cognitive DA, language DA and motor DA at 24 months relative to baseline, and evolution of VABS-II scores as compared to NH data.

The mean rate of DQ decline over 24 months in subjects of the younger ancillary cohort (-1.0 ± 0.5 percentage points/month, mean ± SD, n=6; range -1.4 to -0.3) was 27% lower than that in age-matched NH subjects (-1.5 ± 0.3 percentage points/month, mean ± SD, n=6; range -1.8 to -1.0), with a p value of 0.037. Additionally, in the same cohort, for subjects who have reached the age of 40 ± 3 months (5 out of 6), the average cognitive DA at 40 ± 3 months (30.2 ± 8.4, mean ± SD, n=5; range 19 to 41) was 48% higher than average cognitive DA of age-matched NH subjects (20.4 ± 6.7, mean ± SD, n=13; range 5 to 27), with a p value of 0.019. All subjects of the younger ancillary cohort attained key secondary efficacy criteria of ≥ 80% stabilization or improvement of cognitive DA, language DA and motor DA. Furthermore, consistent with the BSID-III results showing sustained increases or stability of development, there was no statistically significant decrease in any of the mean VABS-II standard scores (total adaptive behavior, communication, daily living skills, socialization, motor skills) from baseline to 24 months post-treatment. Gray matter volume is known to decrease in children with MPS IIIA and to be closely associated with cognitive decline. In the ancillary cohort of younger patients treated with LYS-SAF302, there was no statistically significant decrease in mean cortical gray matter volume from baseline to 24 months post-treatment, in line with preservation of cognitive function in this patient population. Data analysis will be completed in Q2 2023 when all subjects enrolled before the age of 30 months will have reached 48 months of age (timepoint for primary efficacy endpoint interim analysis for the ancillary cohort).