Real-Life Effectiveness After Switching to Avalglucosidase Alfa in Late-Onset Pompe Disease Patients Worsening on Alglucosidase Alfa Therapy: A French Cohort Study.

UNLABELLED: Late-onset Pompe disease (LOPD) is a progressive myopathy. Enzyme replacement therapy is effective, but long-term outcomes vary. Avalglucosidase alfa, shown to be non-inferior to alglucosidase alfa in a phase 3 trial, became available in France through compassionate use for patients with insufficient response to alglucosidase alfa.

METHODS

Data from the French Pompe registry were analyzed for patients who switched to avalglucosidase alfa with at least 1 year of follow-up. Respiratory function (forced vital capacity, FVC) and motor function evaluated with gait performance (Six-Minute Walk Test, 6MWT) were assessed before the switch, and one and 2 years after. Individual changes were compared using paired-sample tests.

RESULTS

Forty-seven adult patients were included. A stabilization of motor decline was observed: prior to switching, the 6MWT decreased by -27 m/year, whereas an improvement of +17 m/year was seen during the first year after the switch (p = 0.001), followed by overall stability in the second year (-10 m/year, p = 0.280). Respiratory changes were not statistically significant: a decline of 60 mL/year before the switch versus 10 mL/year after 1 year (p = 0.161), and 20 mL/year during the second year (p = 0.346). Three patients died during follow-up, with causes unrelated to the disease or treatment.

DISCUSSION: Gait deterioration halted during the first year after transitioning to avalglucosidase, with sustained stabilization thereafter, while respiratory parameters showed minimal change. For patients experiencing significant walking decline under alglucosidase alfa therapy, switching to avalglucosidase alfa resulted in disease stabilization, beginning with mild improvement in the first year and a return to pre-switch baseline thereafter.