The following article features coverage from the 17th Annual WORLDSymposium meeting. Click here to read more of MPR’s conference coverage.

Treatment with avalglucosidase alfa demonstrated clinically meaningful improvements in patients with late-onset Pompe disease (LOPD) compared with alglucosidase alfa, according to results from the phase 3 COMET trial presented at the 17th Annual WORLDSymposium.

Pompe disease is a rare, degenerative muscle disorder caused by mutations in the acid alpha-glucosidase (GAA) gene, which leads to the abnormal buildup of glycogen in tissues and subsequent organ impairment. Avalglucosidase alfa is an investigational GAA enzyme replacement therapy designed for enhanced M6P-receptor targeting and enzyme uptake to increase glycogen clearance.

The multicenter, randomized, double-blind COMET trial compared the efficacy and safety of avalglucosidase alfa to alglucosidase alfa in 100 treatment-naïve patients with LOPD. Patients were randomly assigned 1:1 to receive avalglucosidase alfa (n=51) or alglucosidase alfa (n=49) administered intravenously every 2 weeks. The primary end point was the change from baseline in percent predicted forced vital capacity (FVC) in an upright position.

Results showed that treatment with avalglucosidase alfa met the primary end point achieving noninferiority to alglucosidase alfa for upright FVC percent predicted at week 49 (P =.0074). Patients treated with avalglucosidase alfa showed greater improvements in upright FVC percent predicted at all timepoints as well as a 2.43% (95% CI: -0.13, 4.99) greater increase in FVC percent predicted at week 49 compared with alglucosidase alfa. Additionally, avalglucosidase alfa demonstrated positive results for all secondary and other efficacy end points, including greater improvements in the 6-Minute Walk Test (meters and percent predicted), with 30.01m (95% CI: 1.33, 58.69) and 4.71% (95% CI: 0.25, 9.17) greater increases, respectively.

With regard to safety, the incidence of treatment-emergent adverse events reported in the avalglucosidase alfa and alglucosidase alfa treatment arms were 86.3% and 91.8%, respectively. There were 5 patients who withdrew from the trial (4 due to adverse events), all of which occurred in the alglucosidase alfa arm. Serious adverse events were reported in 8 avalglucosidase alfa-treated patients and 12 alglucosidase alfa-treated patients.

Study authors concluded that “these results demonstrate substantial improvements in clinically meaningful outcome measures as well as a more favorable safety profile in patients with LOPD treated with avalglucosidase alfa compared to alglucosidase alfa.”

Disclosure: Some authors have declared affiliations with or received funding from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.


Kishnani PS, Attarian S, Borges JL, et al. Efficacy and safety results of the avalglucosidase alfa phase 3 COMET trial in late-onset Pompe disease patients. Presented at: 17th Annual WORLDSymposium; February 8-12, 2021. Abstract 121.