Sanofi's Nexviazyme Meets All Endpoints in Phase III Baby-COMET Trial for Infantile-Onset Pompe Disease
Key Insights
Nexviazyme (avalglucosidase alfa) met its primary endpoint of alive and free of invasive ventilation at 52 weeks in treatment-naïve infants aged zero to six months with infantile-onset Pompe disease (search).
All secondary endpoints were also met, including survival free of invasive ventilation at 12 and 18 months, plus numerical improvements in cardiac and motor outcomes.
The single-arm, open-label Baby-COMET study enrolled 17 patients; safety was consistent with the established profile, with no serious treatment-related adverse events or deaths.
Sanofi reported that its next-generation enzyme replacement therapy (ERT) Nexviazyme (avalglucosidase alfa) met all primary and secondary endpoints in the Baby-COMET Phase III study, a pivotal trial evaluating the drug in treatment-naïve infants with infantile-onset Pompe disease (search) (IOPD). The results, announced June 30, 2026, position Nexviazyme for a potential US label expansion that could extend its reach into the most severe and time-critical patient population in Pompe disease — one where the only currently approved option is Sanofi's own older ERT, Myozyme (alglucosidase alfa), approved in 2006.
"Infantile-onset Pompe disease (search) is a devastating, rapidly progressive condition that presents within the first days or weeks of life, making early intervention critical to help improve invasive ventilator-free survival beyond one year," said Priya S. Kishnani, MD, C.L. and Su Chen Professor of Pediatrics and Division Chief of Medical Genetics at Duke University Medical Center. "The Baby-COMET study shows the potential of avalglucosidase alfa to support ventilator-free survival in infants, alongside encouraging cardiac and motor outcomes, offering important insights that may help advance the treatment landscape for these patients."
Trial Design and Endpoints
Baby-COMET is a single-arm, open-label, international, multicenter Phase III study (NCT04910776) that enrolled 17 treatment-naïve pediatric participants with IOPD aged 12 months and younger. Participants received intravenous Nexviazyme at a dose of 40 mg/kg every other week. After a four-week screening period, patients received treatment for 52 weeks, followed by continued treatment for an additional 52 weeks and up to 104 additional weeks, with a four-week follow-up.
The primary endpoint — the proportion of participants aged six months and younger who were alive and free of invasive ventilation at Week 52 — was met. All key secondary endpoints were also met, including the proportion of participants alive and free of invasive ventilation at 12 and 18 months of age, as well as numerical improvements in left ventricular mass Z-score, Alberta Infant Motor Scale score, and urinary glucose tetrasaccharide at 52 weeks.
The small cohort size reflects the rarity and severity of IOPD, where rapid disease progression limits the feasibility of large controlled trials. The single-arm design, without a randomized comparator, means that efficacy interpretation is contextual rather than head-to-head. Cross-trial comparisons with historical alglucosidase alfa data are limited by differences in patient populations, endpoints, and era of treatment.
Safety Profile
Nexviazyme was well tolerated in the Baby-COMET study, with safety consistent with the established profile of avalglucosidase alfa. No serious treatment-related treatment-emergent adverse events, deaths, or discontinuations were reported. Infusion-associated reactions occurred in 29.4% of participants, a rate within the range seen in prior studies of the molecule.
Mechanistic Rationale
Nexviazyme was engineered with approximately 15-fold higher mannose-6-phosphate (M6P) receptor binding affinity compared to alglucosidase alfa, designed to improve lysosomal uptake and enhance glycogen clearance in target tissues. In late-onset Pompe disease (search) (LOPD), the COMET Phase III trial previously demonstrated superiority over alglucosidase alfa on motor and respiratory function endpoints, establishing the mechanistic advantage in a controlled setting. The Baby-COMET data now extend that clinical story into IOPD, though without a randomized comparator arm.
Regulatory Landscape and Next Steps
Nexviazyme currently holds FDA approval for LOPD in patients one year of age and older, granted in 2021. In Europe, where the medicine is available under the name Nexviadyme, it received approval for long-term ERT in patients with Pompe disease covering both LOPD and IOPD in 2022. In the US, however, IOPD treatment-naïve infants have been limited to Myozyme. Nexviazyme in IOPD remains under clinical investigation in the US, and its safety and efficacy in this indication have not yet been evaluated by the FDA.
Sanofi intends to submit the Baby-COMET data to support a US regulatory label extension in the second half of 2026. Full data will be presented on July 8, 2026, at the 19th International Congress on Neuromuscular Diseases in Florence, Italy.
"These positive results offer the potential to expand access of Nexviazyme to more patients and families facing a condition with limited treatment options in the earliest months of life," said Christopher Corsico, Global Head of Development at Sanofi. "The Baby-COMET findings are consistent with previous studies and reflect years of our scientific research aimed at translating deep biological understanding into clinical advances for the Pompe community."
Disease Background
Pompe disease is a rare, inherited, progressive neuromuscular disease caused by a deficiency of the acid alpha-glucosidase (search) (GAA) enzyme, resulting in glycogen accumulation in muscle cells throughout the body and potentially irreversible damage to skeletal and cardiac muscles. IOPD constitutes the most aggressive variant, manifesting with swift symptom progression during the first months of life. Without therapeutic intervention, IOPD can lead to heart failure and death within the first year of life.