Avalglucosidase alfa has a positive clinical impact on motor and cardiac function in patients with infantile-onset Pompe disease (IOPD), according to results from the phase 2 Mini-COMET clinical trial published in Genetics in Medicine and presented at the American College of Medical Genetics and Genomics Annual Clinical Genetics Meeting 2022.

The open-label, ascending dose study enrolled 22 patients with IOPD, aged 1 to 12 years. All patients had previously been treated with alglucosidase alfa for at least 6 months. However, they either showed a suboptimal response to treatment or had a clinical decline.

For Mini-COMET, participants were divided into 3 groups. Those in the first and second groups received 20 mg/kg and 40 mg/kg of avalglucosidase alfa, respectively, every 2 weeks. Those in the third group either received 40 mg/kg of avalglucosidase alfa every 2 weeks or alglucosidase alfa at their pre-enrollment dose. All participants then continued onto an open-label extension phase and received 20 mg/kg, 40 mg/kg, or their maximum tolerated dose of avalglucosidase alfa every other week.

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There were no treatment-related serious adverse events, treatment-emergent severe adverse events, or deaths during the trial. However, all participants had treatment-emergent adverse events, with 11 having events that could be related to treatment. The most common adverse events were rash, fall, upper respiratory tract infection, pneumonia, pyrexia, headache, and vomiting.

The higher dose of avalglucosidase alfa was well-tolerated and had no increased safety risks in participants who switched from alglucosidase alfa. The immune response of participants who switched from alglucosidase alfa was also modest, with similar antidrug antibody peak titers between the 2 treatments.

Moreover, the motor function of most participants receiving avalglucosidase alfa remained stable or improved. The cardiac function of 1 participant improved after switching to avalglucosidase alfa, and at the end of the trial, all participants had a normal cardiac function. Levels of muscle damage and glycogen burden biomarkers, which were elevated for all participants at baseline, trended towards the upper limits of normal with time.

Avalglucosidase alfa has a 15-fold increase in mannose-6-phosphate content compared to alglucosidase alfa, which improves its uptake, glycogen clearance, and clinical efficacy. It is approved for patients with late-onset Pompe disease aged 1 year and above in the US and for all patients with the disease in Japan.


Kronn D, Davison J, Brassier A, et al. OP016: Mini-COMET: safety and efficacy of ≥97 weeks’ avalglucosidase alfa in infantile-onset Pompe disease participants previously treated with alglucosidase alfa. Genet Med. 2022;24(3):S348-S349. doi:10.1016/j.gim.2022.01.566