OBJECTIVES: To describe the outcome of switching from alglucosidase alfa (ALG) to avalglucosidase alfa (AVA) on respiratory function in patients with LOPD.

METHODS: Data for the change in forced vital capacity (ΔFVC) %predicted were analyzed from individuals that received ALG (n=49) during the primary analysis period (PAP) of the phase 3, randomized, double-blind COMET study (NCT02782741) and then switched to AVA (n=44) during the open label extended treatment period (ETP). Prior presented data at week 97 demonstrated group mean responses for these subjects that were minimally changed pre- and post-switch from ALG to AVA. The present post-hoc analysis extends these observations by expanding the ETP to week 145 and dividing patients into two subgroups based on individual responses of FVC during ALG, using a threshold for ΔFVC at week 49 of 3% predicted to reflect clinically meaningful improvement. Piecewise linear mixed effects modelling was used to derive the slope of FVC %predicted/year in each subgroup pre- (baseline–week 49) and post-switch (week 49–week 145).

RESULTS: The study population comprised 44 ALG subjects enrolled in the ETP (24 males) with mean±SD age 49.1±14.0 years, disease duration since symptom onset 12.5±9.8 years, and baseline FVC 61.4±12.5 %predicted, with similar characteristics between the two subgroups. Patients with ΔFVC ≥3% (n=14) demonstrated an increase in FVC during ALG (slope, 4.67±1.28%/yr, p<0.001) that was maintained after switch to AVA (slope, 0.14±0.94%/yr, p=0.88). Although patients with ΔFVC <3% (n=30) demonstrated a reduction in FVC while on ALG (slope, −2.10±0.87%/yr, p=0.016), the decline in respiratory function was halted after switch to AVA (slope, 0.15±0.61%/yr, p=0.81).

CONCLUSIONS: These data suggest clinical benefits over 2 years following a switch of therapy to AVA in patients with LOPD regardless of their prior response to ALG and can inform patient and health care providers decisions regarding treatment options for LOPD.