Pombiliti (cipaglucosidase alfa-atga) / Amicus, BioMarin - LARVOL DELTA

ZIP Study-OL Study of Safety, PK, Efficacy, PD, Immunogenicity of ATB200/AT2221 in Pediatrics Aged 0 to < 18 y.o. w/LOPD (clinicaltrials.gov) - P3 | N=21 | Active, not recruiting | Sponsor: Amicus Therapeutics | Trial completion date: Jun 2026 ➔ Sep 2027 | Trial primary completion date: Jun 2026 ➔ Mar 2027

Trial completion date • Trial primary completion date • Pediatrics • 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

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

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

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

Real word data on alglucosidase – cipaglucosidase/miglustat switching in LOPD: an Italian multiCenter experience. (EAN 2026) - No abstract available

Clinical

ROSSELLA: A Study to Evaluate the Safety, Efficacy, PK, PD and Immunogenicity of Cipaglucosidase Alfa/Miglustat in IOPD Subjects Aged 0 to <18 (clinicaltrials.gov) - P3 | N=36 | Recruiting | Sponsor: Amicus Therapeutics | N=16 ➔ 36

Enrollment change • Metabolic Disorders • Pediatrics • Pompe Disease

90-month Muscle Function and Biomarker Outcomes With Cipaglucosidase Alfa Plus Miglustat (Cipa+Mig) in Adults With Pompe Disease in ATB200-02, an Open-label Phase I/II Study (AAN 2026) - P1/2 | "Across patient populations, long-term treatment with cipa+mig demonstrated durable stability or improvements in muscle function and biomarker outcomes over 7.5 years, with consistent trends despite the inherent variability of small patient cohorts, especially at later time points. Supported by Amicus Therapeutics, Inc."

Biomarker • Clinical • P1/2 data • 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

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

90-Month Efficacy Outcomes with Cipaglucosidase Alfa plus Miglustat in Adults with Pompe Disease in ATB200-02, an Open-Label Phase I/II Study (ACMG 2026) - P1/2 | "Long-term treatment with cipa+mig demonstrated durable stability or improvements in muscle, pulmonary, biomarkers and patient-reported outcomes across Pompe disease populations over 7.5 years. Trends were evident despite the inherent variability of small participant cohorts, which particularly affected the later time points. Supported by Amicus Therapeutics, Inc."

Clinical • P1/2 data • B Cell Lymphoma • Dermatology • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Immunology • Lymphoma • Non-Hodgkin’s Lymphoma • Pompe Disease • Septic Shock • Urticaria

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

ROSSELLA: A Study to Evaluate the Safety, Efficacy, PK, PD and Immunogenicity of Cipaglucosidase Alfa/Miglustat in IOPD Subjects Aged 0 to <18 (clinicaltrials.gov) - P3 | N=36 | Recruiting | Sponsor: Amicus Therapeutics | Trial completion date: Apr 2027 ➔ Jul 2027 | Trial primary completion date: Apr 2027 ➔ Jul 2027

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

New advances in treating late-onset Pompe Disease: A narrative review. (PubMed, Eur J Pediatr) - " Three approved ERT options-alglucosidase alfa, avaglucosidase alfa, and cipaglucosidase alfa + miglustat-are now available for LOPD management and should be considered therapeutic alternatives rather than adjunctive or emerging treatments. Avaglucosidase alfa remains the most effective treatment option with fewer adverse effects. Based on the Triple-S consensus, switching between ERTs should be considered in cases of suboptimal response, intolerance, or significant adverse events, to ensure individualized and optimized patient care. Also, cipaglucosidase alfa + miglustat and clenbuterol might improve the motor and respiratory status but have potential adverse effects."

Journal • Review • Cardiovascular • Gene Therapies • Pompe Disease

Cipaglucosidase alfa plus miglustat in Pompe disease: two non-ambulatory patients switching from high‑dose, high-frequency alglucosidase alfa. (PubMed, Neuromuscul Disord) - "We analyzed outcomes in two non-ambulatory patients in study ATB200-02 who received alg for >13 years (including >2 years' HDHF) before switching to cipa+mig (20 mg/kg + 260 mg every 2 weeks). The two patients experienced 11 non-serious adverse events (no infusion-associated reactions). Data provide information for clinicians considering a transition from HDHF alg to cipa+mig."

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

Predicting PICOs for EU HTA: The Validated PICO Planner Approach Based on Retrospective Analysis (ISPOR-EU 2025) - "Exercises were conducted for four products across oncology (Pluvicto and non-small cell lung cancer [NSCLC]), rare disease (Pombiliti), and type 2 diabetes (T2DM). The findings demonstrate that a structured, data-driven approach to evidence collection and consolidation can predict PICOs. These predictions can be further supported through validation with country affiliates and systematic literature reviews. This approach fosters collaboration with HTA stakeholders, enhances evidence planning, accelerates reviews, and promotes equitable, value-based access—positioning secondary research as a strategic enabler of patient-centered innovation across Europe."

Retrospective data • Diabetes • Lung Cancer • Metabolic Disorders • Non Small Cell Lung Cancer • Rare Diseases • Solid Tumor • Type 2 Diabetes Mellitus

A Disease Progression Model Comparing Respiratory and Motor Decline in People With Late-Onset Pompe Disease Treated With Cipaglucosidase Alfa Plus Miglustat vs. Alglucosidase Alfa (ISPOR-EU 2025) - P1/2, P3 | "Given limited studies on lifetime trajectory of people with LOPD treated with ERT, we modelled long-term disease progression for people receiving alglucosidase alfa (alg) or cipaglucosidase alfa + miglustat (cipa+mig). A patient-level simulation model estimated lifetime mobility and respiratory disease progression outcomes among people with LOPD treated with cipa+mig versus alg based on 6-minute walk distance and % predicted forced vital capacity. In this model, cipa+mig delayed disease progression compared with alg in people with LOPD, increasing the time they did not depend on mobility and respiratory support. While data on progression to respiratory and mobility support are limited, this model, informed by clinical and real-world evidence and expert input, suggests potential for cipa+mig to provide quality-of-life benefits for people with LOPD compared with alg."

Pompe Disease • Rare Diseases • Respiratory Diseases

Effect size analysis of cipaglucosidase alfa + miglustat versus alglucosidase alfa in ERT-experienced adults with late-onset Pompe disease in PROPEL (SSIEM 2023) - No abstract available

Clinical • Pompe Disease

104-week efficacy and safety of cipaglucosidase alfa+miglustat in patients with late-onset Pompe disease previously treated with alglucosidase alfa (SSIEM 2023) - No abstract available

Clinical • Pompe Disease

Safety of home administration of cipaglucosidase alfa + miglustat in late-onset Pompe disease: results from multiple clinical trials (SSIEM 2023) - No abstract available

Clinical • Pompe Disease

Effect size analysis of cipaglucosidase alfa + miglustat versus alglucosidase alfa in ERT-experienced adults with late-onset Pompe disease in PROPEL (SSIEM 2023) - No abstract available

Clinical • Pompe Disease

104-week efficacy and safety of cipaglucosidase alfa+miglustat in patients with late-onset Pompe disease previously treated with alglucosidase alfa (SSIEM 2023) - No abstract available

Clinical • Pompe Disease

Safety of home administration of cipaglucosidase alfa + miglustat in late-onset Pompe disease: results from multiple clinical trials (SSIEM 2023) - No abstract available

Clinical • Pompe Disease

Effect size analysis of cipaglucosidase alfa + miglustat versus alglucosidase alfa in ERT-experienced adults with late-onset Pompe disease in PROPEL (SSIEM 2023) - No abstract available

Clinical • Pompe Disease