Nexviazyme (avalglucosidase alfa) / Sanofi - LARVOL DELTA

Impact of Enzyme Replacement Therapy on Respiratory Function in a Patient with Late-onset Pompe Disease (ERS 2026) - "ERT with avalglucosidase alfa led to marked clinical improvement... ERT may stabilize or improve respiratory function in LOPD. This case demonstrates improvement of respiratory function, highlighting the importance of early diagnosis and timely initiation of ERT."

Clinical • Asthma • Immunology • Lysosomal Storage Diseases • Metabolic Disorders • Myositis • Obstructive Sleep Apnea • Pompe Disease • Pulmonary Disease • Rare Diseases • Respiratory Diseases • Sleep Disorder

Avalglucosidase Alfa French Post-trial Access for Participants With Pompe Disease (PTA Avalglucosidase) (clinicaltrials.gov) - P4 | N=17 | Active, not recruiting | Sponsor: Genzyme, a Sanofi Company | Trial completion date: Sep 2026 ➔ Jun 2027 | Trial primary completion date: Sep 2026 ➔ Jun 2027

Trial completion date • Trial primary completion date • Metabolic Disorders • Pompe Disease

Alglucosidase alfa to avalglucosidase alfa switch improves biomarkers in infantile-onset Pompe disease: Pompe Registry analysis (SSIEM 2026) - P | "Patients with IOPD showed improved CK, Hex4, ALT, and AST trajectories after switching from Alg to Ava. Improvements were observed for both label-dose and high-dose Alg patients who switched to Ava."

Biomarker • Pompe Disease

Enhancing Enzyme Replacement Therapy in Lysosomal Storage Disorders: Faster Infusion Rates Across the UK (SSIEM 2026) - "Frequently accelerated treatments included agalsidase beta, alglucosidase alfa, avalglucosidase alfa, cipaglucosidase alfa with miglustat, laronidase, elosulfase, idursulfase, and galsulfase. Accelerated ERT infusion rates outside SmPC recommendations are already in widespread use across UK LSD centres without evidence of elevated infusion-related adverse events. While practice varies, centres successfully shorten treatment duration by modifying infusion protocols. Wider sharing of local protocols and outcomes may improve equity for patients across centres, reduce treatment burden and shorter nursing homecare visits which in turn will reduce financial burden to the NHS."

Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Defining the therapeutic corridor of stability in enzyme replacement therapy for Pompe disease: a position statement. (PubMed, Orphanet J Rare Dis) - "This formal, multi-domain therapeutic corridor of stability for enzyme replacement therapy in Pompe disease is grounded in available Phase 2, Phase 3, extension, registry, consensus, and real-world evidence. The framework supports structured monitoring, timely reassessment of treatment, and personalized management for patients receiving long-term enzyme replacement therapy. Prospective validation with standardized monitoring is required."

Journal • Review • Lysosomal Storage Diseases • Metabolic Disorders • Pompe Disease • Rare Diseases

Real-Life Effectiveness After Switching to Avalglucosidase Alfa in Late-Onset Pompe Disease Patients Worsening on Alglucosidase Alfa Therapy: A French Cohort Study. (PubMed, Eur J Neurol) - "Gait deterioration halted during the first year after transitioning to avalglucosidase, with sustained stabilization thereafter, while respiratory parameters showed minimal change. For patients experiencing significant walking decline under alglucosidase alfa therapy, switching to avalglucosidase alfa resulted in disease stabilization, beginning with mild improvement in the first year and a return to pre-switch baseline thereafter."

Journal • Myositis • Pompe Disease

A Comprehensive Update on Pompe Disease: From Existing Therapies to Emerging Curative Strategies. (PubMed, Int J Mol Sci) - "Next, we critically discuss the advantages and limitations of current ERT approaches, and advances achieved with next-generation ERT (avalglucosidase alfa, cipaglucosidase alfa + miglustat). Finally, we summarize cutting-edge, potentially curative strategies, including substrate reduction therapy and novel experimental therapies (e.g., gene therapy) that seek to circumvent the limitations of ERT, provide durable effects, and potentially penetrate the central nervous system."

Journal • Review • Cardiomyopathy • Cardiovascular • CNS Disorders • Gene Therapies • Hypertrophic Cardiomyopathy • Pompe Disease • Respiratory Diseases

Safety and Efficacy of an Enzyme Replacement Therapy in Infantile‑Onset Pompe Disease (ICNMD 2026) - P3 | "In 2006, alglucosidase alfa, a recombinant human acid alpha glucosidase (rhGAA) was approved for the treatment of IOPD based on prolonged ventilator-free survival. The Baby-COMET study is one of the largest clinical studies in treatment-naïve patients with IOPD. The results of the Baby-COMET study have the potential to support use of avalglucosidase alfa in treatment-naïve infants living with Pompe disease."

Clinical • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Pompe Disease

Switching From Alglucosidase Alfa to Avalglucosidase: Real-World Data From a Single-Center Experience (ICNMD 2026) - "To provide real-life data is critical for understanding long-term treatment effects outside controlled trial environments. About 10/11 improved or stabilized, one pt who switched from alglucosidase-alfa to avalglucosidase-alfa after a period of gradual decline, did not inverted this trend after switching, likely due to limited residual muscle function. Notably, ERT-naïve pt had stable motor and respiratory function over eight years with avalglucosidase-alfa."

Clinical • Real-world • Real-world evidence • CNS Disorders • Pompe Disease

A Novel Cohort of Italian Patients With Late-Onset Pompe Disease and Extended IVS1-32-13T>G Screening (ICNMD 2026) - "Eleven patients are currently receiving enzyme replacement therapy (ERT): 6 with alglucosidase alfa biweekly and 5 with avalglucosidase alfa as replacement for alglucosidase alfa. This cohort demonstrates significant phenotypic variability with predominant IVS1 variant, underscoring the necessity of targeted molecular screening for early diagnosis and personalized therapeutic monitoring."

Clinical • Musculoskeletal Pain • Myositis • Pompe Disease

Real-world Outcomes of Very Early-treated Infantile-onset Pompe Disease in Taiwan After Switching to Avalglucosidase Alfa (ICNMD 2026) - "Very early initiation of enzyme replacement therapy enabled by nationwide newborn screening and rapid diagnostic strategies is associated with improved long-term outcomes in infantile-onset Pompe disease. The additional and sustained benefits observed after switching to next-generation ERT with avalglucosidase alfa further support this integrated treatment approach for long-term management of IOPD."

Clinical • Real-world • Real-world evidence • Pompe Disease

Impact of Enzyme Replacement Therapy on Patients with Late Onset Pompe Disease - Real World Data from a Developing Country. (PubMed, Indian J Pediatr) - "This is the first study describing the impact of ERT in an Indian cohort of LOPD patients. It shows real world concerns of impact of chronic diseases with delay in starting therapy. It also brings to light the challenges in obtaining multi-disciplinary management. The wide variability in spectrum of presentations, early onset and faster rates of disease progression as well as high disease burden highlight the need for early initiation of therapy."

Journal • Real-world evidence • CNS Disorders • Infectious Disease • Muscular Dystrophy • Novel Coronavirus Disease • Pompe Disease • Sleep Disorder

Combined omalizumab and desensitization to control IgE-mediated hypersensitivity in enzyme replacement therapy for late-onset Pompe disease. (PubMed, Orphanet J Rare Dis) - "This case highlights the critical role of BAT in diagnosing and monitoring IgE-mediated HSRs, the efficacy of individualized desensitization protocols, and the utility of omalizumab as an adjunctive therapy in refractory cases. In rare diseases like Pompe, documenting such integrated allergological strategies provides practical guidance for maintaining access to life-prolonging therapy and offers a reproducible framework for managing complex allergic complications."

Journal • Allergy • Immunology • Lysosomal Storage Diseases • Metabolic Disorders • Pompe Disease • Rare Diseases

Baby-COMET: Clinical Study for Treatment-naïve IOPD Babies to Evaluate Efficacy and Safety of ERT With Avalglucosidase Alfa (clinicaltrials.gov) - P3 | N=17 | Active, not recruiting | Sponsor: Sanofi | Completed ➔ Active, not recruiting

Enrollment closed • Metabolic Disorders • Pediatrics • Pompe Disease

GZ-2016-11512: Safety and efficacy of avalglucosidase alfa in patients with non-classic Pompe disease aged ? 5 years. (clinicaltrialsregister.eu) - P4 | N=6 | Recruiting | Sponsor: Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC) | Not yet recruiting ➔ Recruiting

Enrollment open • Metabolic Disorders • Pompe Disease

Case Report: Clinical and Genetic Characterization of Late-onset Pompe Disease in an Adolescent Carrying a Rare GAA Coding Mutation (AAN 2026) - "Enzyme replacement therapy (ERT) with avalglucosidase alfa (20 mg/kg every two weeks) was initiated...Integrating enzymatic, genetic, and functional assessments enables precise characterization of disease phenotype. Timely initiation of enzyme replacement therapy, complemented by structured multidisciplinary follow-up, may reshape the natural history of LOPD, optimizing long-term neuromuscular and respiratory outcomes."

Case report • Clinical • CNS Disorders • Epstein-Barr Virus Infections • Immunology • Infectious Disease • Metabolic Disorders • Musculoskeletal Pain • Myositis • Pompe Disease

Baby-COMET: Clinical Study for Treatment-naïve IOPD Babies to Evaluate Efficacy and Safety of ERT With Avalglucosidase Alfa (clinicaltrials.gov) - P3 | N=17 | Completed | Sponsor: Sanofi | Active, not recruiting ➔ Completed

Trial completion • Metabolic Disorders • Pediatrics • Pompe Disease

Early enzyme replacement therapy in late-onset Pompe disease diagnosed by newborn screening. (PubMed, Mol Genet Metab) - "Data presented here supports existing evidence that infants and children with LOPD can present with early symptom onset and may benefit from early ERT. While further study is needed, we showcase the early features of LOPD, benefits from early ERT, and the importance of comprehensive multidisciplinary evaluation of LOPD diagnosed via NBS, allowing timely intervention for those that may benefit from early ERT."

Journal • Metabolic Disorders • Pompe Disease

Treatment frequency Reduction In POmpe disease (TRIPO-Study) (clinicaltrialsregister.eu) - P4 | N=10 | Recruiting | Sponsor: Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC) | Not yet recruiting ➔ Recruiting

Enrollment open • Pompe Disease

Comprehensive review of recent advances in Pompe disease: pathogenesis, management, and future directions. (PubMed, Front Neurol) - "Next-generation ERTs, including avalglucosidase alfa and cipaglucosidase alfa combined with miglustat, have improved outcomes and safety...Despite progress, challenges remain in early detection, long-term management, and healthcare resource allocation. Future success requires integrated strategies combining NBS, innovative therapeutics, sensitive monitoring, and supportive policies."

Journal • Review • Gene Therapies • Lysosomal Storage Diseases • Metabolic Disorders • Pompe Disease • Rare Diseases

Comparing the efficacy of cipaglucosidase alfa plus miglustat with alglucosidase alfa for late-onset Pompe disease: an expanded network meta-analysis utilizing patient-level and aggregate data. (PubMed, J Comp Eff Res) - "Aim: Treatment options for late-onset Pompe disease (LOPD) include enzyme replacement therapy (ERT) with alglucosidase alfa (alg), cipaglucosidase alfa plus miglustat (cipa + mig) and avalglucosidase alfa...Materials & A Bayesian ML-NMR was conducted to compare the efficacy of cipa + mig and alg for 6-minute walk distance (6MWD, meters) and percent predicted forced vital capacity (ppFVC) across any target population, using patient-level and aggregate data from RCTs (PROPEL, COMET, LOTS) and phase I/II and open-label extension (OLE) trials (PROPEL OLE, LOTS OLE, COMET OLE, ATB200-02, NEO-1/NEO-EXT), adjusting for baseline covariates... Cipa + mig was associated with an improvement in 6MWD and ppFVC relative to alg independent of prior ERT exposure, which appeared more favorable when all available evidence was used. These data could inform decision-making in treating ERT-naive and ERT-experienced patients with LOPD."

Journal • Retrospective data • Myositis • Pompe Disease

Short-Term Intensive Avalglucosidase Alfa Regimen in Late-Diagnosed Infantile Pompe Disease: A Case Report. (PubMed, Reports (MDPI)) - "Clinical trials, conducted on IOPD patients already treated with alglucosidase alfa, have recommended a dosage ranging from 20 to 40 mg/kg every other week. At 18 months of age, the patient demonstrated normal motor development, normal cardiac function (LVMI of 49 g/m2; EF of 68%), and normal biomarkers. Although limited to a single patient, this case illustrates that short-term high-dose, high-frequency administration of avalglucosidase alfa could be both effective and safe, even in patients with severe, late-diagnosed IOPD."

Journal • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Pompe Disease

Enzyme replacement therapy compared with best supportive care for the treatment of Pompe Disease: a systematic review and network meta-analysis. (PubMed, Health Technol Assess) - "However, there is limited evidence to suggest meaningful differences in outcomes between alglucosidase alfa, avalglucosidase alfa and cipaglucosidase alfa with miglustat. Long-term comparative effectiveness remains uncertain, as does enzyme replacement therapy's impact on disease progression and supportive care needs. This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis programme as award number NIHR161219."

Journal • Retrospective data • Review • Metabolic Disorders • Pompe Disease • Respiratory Diseases

First multicenter real-world analysis of switching to next-generation enzyme replacement therapies in late-onset Pompe disease. (PubMed, J Neurol) - "This real-world study suggests that transitions between ERT preparations are generally feasible and associated with clinical stability in LOPD. Switching may represent a useful strategy in patients, particularly when efficacy concerns arise. Standardized prospective studies with systematic monitoring of immunogenicity and efficacy according to the 2024 EOPC guideline are recommended to confirm these findings."

Journal • Observational data • Real-world evidence • CNS Disorders • Pompe Disease

The Telltale Hearts: Infantile Onset Pompe Disease in an Age of Expanding Treatment Options (ACMG 2026) - "Patient A received alglucosidase alfa from 6 weeks to 6 years of life...One 40 mg/kg avalglucosidase alfa infusion was given on DOL 22... We present three clinically and molecularly distinct cases of IOPD, describing each course's impact on the following. Patient A showed that immunological complications can have a profound effect on therapy tolerance, and changing to newer ERT may take a year to show clinical improvement. Patient B and C taught us in the era of ERT that the first or presenting symptoms of IOPD may be arrhythmias; awareness of the severity and duration of arrhythmias is crucial for care of these patients in the neonatal period."

Cardiomyopathy • Cardiovascular • Immune Modulation • Immunology • Metabolic Disorders • Pompe Disease • KMT2C