Myozyme (alglucosidase alfa) / Sanofi - LARVOL DELTA

The Effect of Anti-drug Antibodies on the Bioavailability of Alglucosidase Alfa in Classic Infantile Pompe Disease. (PubMed, BioDrugs) - "High ADAs have heterogenous effects on rhGAA bioavailability. Titers ≥1:156,250, mostly, had a measurable effect, capturing up to > 50% of infused rhGAA. A high titer, per se, did not imply neutralizing effects. Where available, functional assays, including PK curves and uptake studies, may contribute to characterize ADA effects."

Journal • Immunology • Pompe Disease

Clinical stabilisation in two patients with infantile-onset Pompe disease treated with cipaglucosidase alfa and miglustat (SSIEM 2026) - "Despite early initiation of enzyme replacement therapy (ERT) with alglucosidase alfa (ALGLU), patients with IOPD often experience clinical deterioration...Since then she received immunomodulation with rituximab, methotrexate and IVIG... Switching to CIPA/MIG, particularly weekly dosing, successfully achieved clinical stabilization and motor improvement in two IOPD patients previously declining despite long-term treatment with ALGLU."

Clinical • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Immunology • Pompe Disease • Respiratory Diseases

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

Pompe Disease: From a Cardiovascular Lens. (PubMed, Cardiol Rev) - "The introduction and approval of enzyme replacement therapy (alglucosidase alfa; Myozyme/Lumizyme) in 2006 dramatically changed the outlook for infantile-onset Pompe disease, transforming what was once a uniformly fatal cardiomyopathy into a treatable condition. Nonetheless, long-term follow-up of patients receiving enzyme replacement therapy has uncovered ongoing cardiac issues; persistent conduction defects, arrhythmias, and residual myocardial fibrosis highlight the need for continued cardiovascular monitoring in these individuals."

Journal • Cardiomyopathy • Cardiovascular • Fibrosis • Immunology • Lysosomal Storage Diseases • Metabolic Disorders • Pompe Disease • Rare Diseases

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 disease progression model comparing the long-term mobility and respiratory outcomes of adults with late-onset Pompe disease receiving cipaglucosidase alfa plus miglustat versus alglucosidase alfa. (PubMed, J Comp Eff Res) - P1/2, P3 | "PROPEL/PROPEL open-label extension (NCT03729362) and ATB200-02 (NCT02675465) studies informed outcomes for four years with cipa + mig and one year with alg. People receiving alg may be wheelchair dependent and require invasive respiratory support for an additional 2.57 and 1.55 years, respectively. Cipa + mig may delay disease progression compared with alg over the lifetime of a patient with LOPD, which would increase the amount of time spent without mobility and respiratory support dependency."

Journal • Pompe Disease • Rare Diseases • 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

Characteristics of Patients with Late-Onset Pompe Disease: Insights from the Romanian Cohort (ICNMD 2026) - "Eight patients received enzyme-replacing treatment (ERT) with alglucosidase alfa, and one had a positive anti-enzyme antibody titer, however without reported adverse reactions... To our knowledge, this is the first study investigating the Romanian LOPD population. Our findings suggest that while the most prevalent genotype is consistent with previously reported studies in Caucasian population, the phenotypic variability remains important. In most patients the respiratory function was largely preserved, however with an important motor impairment."

Clinical • Cardiovascular • CNS Disorders • Gastrointestinal Disorder • Ischemic stroke • 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

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

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

Alglucosidase alfa demonstrates effectiveness and safety in Chinese patients with late-onset Pompe disease: A multi-center prospective study. (PubMed, Mol Genet Metab) - "Alglucosidase alfa demonstrated a positive benefit-risk profile in Chinese LOPD patients, confirming its safety and effectiveness."

Journal • 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

Miglustat: a first-in-class enzyme stabilizer for cipaglucosidase alfa for the treatment of late-onset Pompe disease. (PubMed, Ther Adv Rare Dis) - P1/2, P3 | "Enzyme replacement therapy (ERT) with alglucosidase alfa, a recombinant human GAA (rhGAA), was the first disease-specific therapy for Pompe disease. In patients with Pompe disease, the once every 2 weeks dosing regimen of miglustat was well tolerated, with a low frequency of miglustat-related gastrointestinal events compared with daily miglustat regimens at higher doses used in the treatment of other diseases. Trial registration: New data are reported for NCT02675465 (ATB200-02), NCT03729362 (PROPEL), and NCT04138277 (PROPEL open-label extension, ATB200-07); all registered at ClinicalTrials.gov (https://clinicaltrials.gov)."

Journal • Review • Genetic Disorders • Pompe Disease • Respiratory 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

Long-Term (208-Week) Efficacy and Safety Outcomes of Cipaglucosidase Alfa+Miglustat in People with Late-Onset Pompe Disease Treated from PROPEL Baseline (ACMG 2026) - P3 | "The efficacy and safety of cipaglucosidase alfa plus miglustat (cipa+mig) versus alglucosidase alfa plus placebo in adults with LOPD were established in the randomized, double-blind, 52-week PROPEL study (NCT03729362). Following 4 years of treatment with cipa+mig, participants with LOPD experienced sustained and durable improvements in muscle function and biomarker levels, as well as stability or improvement in pulmonary function. These data support the long-term benefits of cipa+mig in people with LOPD. Supported by Amicus Therapeutics, Inc."

Clinical • Lewy Body Disease • Pompe Disease

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