Itvisma

Itvisma is indicated for the treatment of 5q spinal muscular atrophy (SMA) with a bi-allelic mutation in the SMN1 gene in patients 2 years of age and older, as per the final CHMP recommended indication. The finished product concentration of onasemnogene abeparovec is 4 x 10^13 vg/mL, with a shelf life of 24 months. The Marketing Authorisation Application was submitted on 29 April 2025, following an orphan medicinal product designation on 19 June 2015.

In efficacy studies, the median survival of SMNΔ7 mice with the highest ICV dose of AVXS-101 was 282 days, compared to 17.5 days for untreated SMNΔ7 mice. Transduced spinal motor neurons with 1.8 x 10^13 vg/kg scAAV9.CBA.GFP in neonatal mice showed 20-40% expression. GFP expression in lumbar motor neurons with an ICV dose of 3.3 x 10^14 vg/kg in mice was 72%. In macaques, GFP expression in the lumbar region with an IT dose of 1 x 10^13 vg/kg was 79.6%.

Safety findings include a systemic exposure reduction of approximately 70-fold lower. Peak shedding in faeces ranged from 0.005% to 0.03% of the total dose. Baseline serum anti-AAV9 antibody titers were ≤1:50, while median serum anti-AAV9 antibody titers at Week 52 were ≥1:819200. Pre-existing anti-SMN antibodies were observed in 1/27 participants, and 5/75 participants were anti-SMN antibody positive.