Avalglucosidase Alfa Meets All End Points in Phase 3 Baby-COMET Trial for Infantile-Onset Pompe Disease

Sanofi's avalglucosidase alfa (Nexviazyme) met its primary and all secondary end points in treatment-naïve infants with infantile-onset Pompe disease (IOPD), according to topline findings from the phase 3 Baby-COMET study (NCT04910776). The positive results, which will be presented at the 2026 International Congress on Neuromuscular Diseases, are expected to support a planned US regulatory submission in the second half of 2026 seeking to expand the therapy's label to include infants with IOPD.¹

“Infantile-onset Pompe disease 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,” Priya S. Kishnani, MD, professor of pediatrics and division chief of Medical Genetics at Duke University, said in a statement.¹ “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 Population

Baby-COMET is a single-arm, open-label, international, multicenter phase 3 study enrolling treatment-naïve participants with IOPD who were 12 months of age or younger at entry. Seventeen participants received intravenous avalglucosidase alfa 40 mg/kg every other week. Following a 4-week screening period, participants completed a 52-week primary analysis period with provisions for continued long-term treatment and follow-up. The primary end point was the proportion of participants alive and free of invasive ventilation at week 52.

Key secondary end points assessed survival free of invasive ventilation at 12 and 18 months of age, and change from baseline to week 52 in left ventricular mass Z-score, Alberta Infant Motor Scale score, and urinary glucose tetrasaccharide, a biomarker reflecting glycogen burden. The study met its primary end point and all prespecified secondary end points, with the company characterizing additional disease progression metrics as numerically improved at 52 weeks.

“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," Christopher Corsico, global head of development at Sanofi, said in a statement.¹ “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.”

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Safety

In the Baby-COMET cohort, avalglucosidase alfa was reported to be well tolerated, with no treatment-related serious adverse events, no deaths, and no treatment discontinuations. Infusion-associated reactions occurred in 29.4% of participants and were described as manageable, consistent with the established safety profile of the drug across prior studies in LOPD and pediatric populations.

Clinical Context and Unmet Need

IOPD is the most severe form of Pompe disease, a rare autosomal recessive lysosomal storage disorder caused by deficiency of acid alpha-glucosidase. Without treatment, classic IOPD is characterized by rapid-onset hypertrophic cardiomyopathy, generalized muscle weakness, and cardiorespiratory failure, with most affected infants dying in the first year of life.²

Enzyme replacement therapy with the first-generation agent alglucosidase alfa (Myozyme/Lumizyme) substantially altered the natural history of IOPD following its approval, yet clinical outcomes remain heterogeneous and depend heavily on timing of treatment initiation, dosing, immune status, and GAA genotype. Real-world data indicate that even among patients identified through newborn screening and treated early, a subset experience progressive motor decline and persistent glycogen accumulation.³

Mechanism and Regulatory History

Avalglucosidase alfa is engineered with approximately 15-fold greater mannose-6-phosphate (M6P) content compared with alglucosidase alfa, intended to enhance receptor-mediated uptake and lysosomal glycogen clearance in target tissues. The FDA approved avalglucosidase alfa in August 2021 for the treatment of LOPD in patients 1 year of age and older, based on the phase 3 COMET trial (NCT02782741), in which the agent demonstrated noninferiority and numerical superiority to alglucosidase alfa on forced vital capacity percent predicted and 6-minute walk distance in treatment-naïve LOPD patients.^4,5 In Europe, the drug received approval in 2022 for both LOPD and IOPD under the marketed name Nexviadyme.

REFERENCES
1. Press Release: Sanofi’s Nexviazyme met all primary and secondary endpoints in infantile-onset Pompe disease phase 3 study. News release. Sanofi. June 30, 2026. Accessed June 30, 2026. https://www.sanofi.com/en/media-room/press-releases/2026/2026-06-30-05-00-00-3319382
2. Kishnani PS, Hwu WL, Mandel H, et al. A retrospective, multinational, multicenter study on the natural history of infantile-onset Pompe disease. J Pediatr. 2006;148(5):671-676. doi:10.1016/j.jpeds.2005.11.033
3. Ditters IAM, Huidekoper HH, Kruijshaar ME, et al. Effect of alglucosidase alfa dosage on survival and walking ability in patients with classic infantile Pompe disease: a multicentre observational cohort study from the European Pompe Consortium. Lancet Child Adolesc Health. 2022;6(1):28-37. doi:10.1016/S2352-4642(21)00308-4
4. Punnoose AR, Jeng LJB, Maynard JW; Review Team. Regulatory news: Avalglucosidase alfa-ngpt (Nexviazyme) for late-onset Pompe disease-FDA approval summary. J Inherit Metab Dis. 2022;45(6):1015-1017. doi:10.1002/jimd.12543
5. Diaz-Manera J, Kishnani PS, Kushlaf H, et al. Safety and efficacy of avalglucosidase alfa versus alglucosidase alfa in patients with late-onset Pompe disease (COMET): a phase 3, randomised, multicentre trial. Lancet Neurol. 2021;20(12):1012-1026. doi:10.1016/S1474-4422(21)00241-6