Long-Term Sustained Benefit Observed in Pompe Treatment Avalglucosidase Alfa


At 97 weeks, avalglucosidase alfa showed continued benefit on measures such as forced vital capacity and 6-minute walk test distance and was successful for patients who switched off algucosidase alfa.

Hani A. Kushlaf, MD, FAAN, FANA, FAANEM

Hani A. Kushlaf, MD, FAAN, FANA, FAANEM

After previously showing positive results in the original 49-week study period, new data from the phase 3 COMET study (NCT02782741) showed a sustained treatment benefit over 97 weeks for patients with late-onset Pompe disease (LOPD) treated with avalglucosidase alfa-ngpt (Nexviazyme; Sanofi). These data were presented at the 2022 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, March 13-16, by Hani A. Kushlaf, MD, FAAN, FANA, FAANEM, associate professor and director of the Neuromuscular Medicine Fellowship, University of Cincinnati.1

Avalglucosidase alva, an enzyme replacement therapy, became FDA-approved for the treatment of LOPD in patients aged 1 year and older in August 2021, with data from COMET and the phase 2 mini-COMET trial (NCT03019406) serving as the basis for approval. In the primary analysis period (PAP) of COMET, the therapeutic demonstrated a 2.9-improvement (SE, 0.9) in forced vital capacity percent-predicted (FVC%) after 49 weeks, equating to a 2.4-point greater improvement (95% CI, –0.13 to 4.99) than those treated with Sanofi’s comparator product, alglucosidase alfa (Lumizyme), in a measurement of noninferiority (P = .0074).2

All 100 participants during the PAP were treatment-naïve. All 51 participants receiving alvaglucosidase alfa 20 mg/kg every 2 weeks (qow) in the PAP continued this regimen in the extended treatment period (ETP)(AVAL-arm) while 44 of the remaining 49 participants who originally received algucosidase alfa 20 mg/kg qow in the PAP entered the ETP and switched to avalglucosidase alfa 20 mg/kg qow (switch-arm).

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At week 97, those in the AVAL-arm demonstrated least square mean changes of 2.65 (SE; 1.05) on FVC% and 18.60 (SE, 12.01) on 6-minute walk test distance (6MWT). Results also showed stabilization of treatment effect after switching, which was represented by changes of 0.36 (SE, 1.12) and 4.56 (SE, 12.44) in FVC% and 6MWT, respectively, at 97 weeks in the switch-arm group.1

In total, 96% of those in the AVAL-arm and 95% of switch-arm patients had treatment-emergent adverse events (AEs). There were 5 discontinuations due to AEs during the ETP. They included ocular hyperemia, erythema, urticaria, and respiratory distress, which were treatment related, as well as acute myocardial infarction and pancreatic adenocarcinoma, which were not treatment-related.

In the ETP, 12 AVAL-arm and 10 switch-arm participants had treatment-emergent serious AEs (SAEs); 3 and 2 of them respectively, had SAEs related to treatment. Investigators observed no safety- or immunogenicity-related concerns for switch-arm patients.

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1. Kushlaf HA, Kishnani P, Diaz-Manera J, et al. The avalglucosidase alfa phase 3 COMET trial in participants with late-onset Pompe disease: efficacy and safety results after 97 weeks. Presented at MDA Clincial and Scientific Conference; March 13-16. Poster 69
2. Krishnani P, Attarian S, Borges JL, et al. Efficacy and Safety Results of the Avalglucosidase alfa Phase 3 COMET Trial. Presented at: WorldSymposium. February 12, 2021. Poster 121.
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