Myozyme (alglucosidase alfa) / Sanofi - LARVOL DELTA

Improving the treatment of pompe disease with enzyme replacement therapy: current strategies and clinical evidence. (PubMed, Expert Opin Pharmacother) - "The first approved ERT for PD was the rhGAA alglucosidase alfa. A brief overview of the newest ERT, cipaglucosidase alfa, is also provided. While ERT for PD continues to improve with more effective enzymes like avalglucosidase alfa, the future lies in integrated approaches that combine different therapeutic modalities (gene therapy, substrate reduction therapy) and the use of biomarkers to individualize treatment."

Journal • Review • Gene Therapies • Genetic Disorders • Metabolic Disorders • Pompe Disease

Successful desensitization protocol to alglucosidase and avalglucosidase alfa in a patient with infantile-onset Pompe disease. (PubMed, Mol Genet Metab Rep) - "We present the case of an infant who developed anaphylaxia to enzyme replacement therapy with alglucosidase-alfa. We provide a desensitization protocol to alglucosidase-alfa and, for the first time, a desensitization protocol to avalglucosidase-alfa, both delivered in a reasonable time of <6 h, and without any further reactions in the patient."

Journal • Cardiomyopathy • Cardiovascular • Pompe Disease • Rare Diseases

Miglustat: A First-In-Class Enzyme Stabilizer for Late-Onset Pompe Disease (P10-2.012). (PubMed, Neurology) - "In a head-to-head study, cipa+mig had a similar safety profile to alglucosidase alfa...Dimachkie has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Cabaletta Bio...Prof. parenti has nothing to disclose."

Journal • Fabry Disease • Gene Therapies • Genetic Disorders • Muscular Dystrophy • Pompe Disease

Five-Year Outcomes of Patients with Pompe Disease Identified by the Pennsylvania Newborn Screen. (PubMed, Int J Neonatal Screen) - "One LOPD patient was started on ERT at age 4.5 months. Continued data collection on these patients is critical for developing management guidelines, including timing of ERT and improved genotype-phenotype correlation."

Journal • Pompe Disease

Analyse des dépenses de santé et des parcours de soins des patients atteints de la maladie de Pompe recevant du Myozyme : une étude observationnelle basée sur les données du système national des données de santé (SNDS). (PubMed, J Epidemiol Popul Health) - "Cette étude fournit des données solides issues du monde réel pour évaluer les coûts hospitaliers et non hospitaliers associés à la maladie de Pompe chez les patients traités avec Myozyme®. Avec une moyenne de 71.6 consultations médicales ou paramédicales par an et 49 jours d'hospitalisation en 2022, la charge clinique imposée par la maladie de Pompe est substantielle, mais essentielle pour les soins aux patients."

Journal

RIDING THE VT STORM : COMPLEX CARE FOR A POMPE DISEASE PATIENT WITH VA-ECMO AND ENZYME REPLACEMENT THERAPY - Liyan Obeidat (ACC 2025) - "She was started on Nexviazyme (avalglucosidase alfa) and received a total of three doses...She was discharged on mexiletine and amiodarone...Alglucosidase alfa has been shown to improve cardiac function, although it does not eliminate the risk of arrhythmias. In Pompe disease, cardiac findings can differ in terms of severity, structures involved, age of onset, and rate at which the condition progresses. In Pompe disease, cardiac findings can differ in terms of severity, structures involved, age of onset, and rate at which the condition progresses. In our case, VT was the first manifestation of the disease and occurred during adulthood. Regular cardiac evaluations, including 24-hour Holter monitoring, are recommended to detect and manage arrhythmias."

Clinical • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Metabolic Disorders • Pompe Disease • Ventricular Tachycardia

Miglustat: A First-In-Class Enzyme Stabilizer for Late-Onset Pompe Disease (AAN 2025) - "In a head-to-head study, cipa+mig had a similar safety profile to alglucosidase alfa. The two-component therapy combining cipa with mig achieved better stabilization of cipa in circulation, improved cipa exposure, further reduced Hex4 levels and was well tolerated in clinical studies in patients with LOPD. Supported by Amicus Therapeutics, Inc."

Pompe Disease

Effect Size Analysis of Cipaglucosidase Alfa Plus Miglustat Versus Alglucosidase Alfa in ERT-experienced Adults with Late-onset Pompe Disease in PROPEL (S21.003). (PubMed, Neurology) - P3 | "The randomized, double-blind PROPEL study (ATB200-03; NCT03729362) compared the efficacy and safety of the investigational two-component enzyme replacement therapy (ERT) cipa+mig with alg plus placebo in adults with late-onset Pompe disease (LOPD); 77% of patients had received ERT with alg before study entry (median ERT duration 7.4 years)...Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cabaletta Bio...Dr. Mozaffar has received personal compensation in the range of $500-$4,999 for serving as a Study Section Member with NIH."

Clinical • Journal • CNS Disorders • Fatigue • Muscular Dystrophy • Pompe Disease • Rare Diseases

Is Brazil following global trends in high-cost treatments? The case of Pompe Disease. (PubMed, J Community Genet) - "Data on the dispensing of alglucosidase alfa from the Brazilian Outpatient Information System (SIA/SUS; Jan 2020-May 2024) were analyzed and compared to previous budget impact estimates...Brazil's access model shows partial alignment with global trends, but significant gaps remain. The study highlights systemic issues that are relevant to other rare diseases, offering insights and lessons for Brazil and other middle-income countries."

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

Efficacy of Transitioning from Alglucosidase Alfa to Avalglucosidase Alfa in Infantile-Onset Pompe Disease: A Single-Center Cohort Analysis. (PubMed, Genet Med) - "The transition from a high dose of AGL to AVA demonstrated sustained improvements in biomarker levels and motor function in patients with IOPD. Early initiation of AVA is crucial for patients with IOPD."

Journal • Immune Modulation • Immunology • Pompe Disease

Management of presymptomatic juvenile patients with late-onset Pompe disease (LOPD). (PubMed, Neuromuscul Disord) - "Four patients started alglucosidase alfa, and one avalglucosidase alfa. These five patients on Enzyme Replacement Therapy (ERT) showed motor and respiratory stability in the following years. Timely identification of emerging clinical manifestations in presymptomatic LOPD patients, as a result of careful follow-up, is essential to start prompt treatment to modify the disease natural course."

Journal • Myositis • Pompe Disease

Press Release: Q4 sales growth of 10.3%, 2024 business EPS guidance exceeded, and strong business EPS rebound expected in 2025 (GlobeNewswire) - "Lantus sales were €439 million and increased by 63.4%. US sales were €193 million...Toujeo sales were €290 million and increased by 6.5%, mainly driven by Europe (+10.1%) and Rest of World (+7.4%) where Toujeo continued to increase its basal insulin market share...Alprolix sales were €169 million and increased by 19.0%, benefiting from an increase in US market share and supply sales to Sobi. Myozyme/Lumizyme sales were €132 million and decreased by 17.0% due to the aforesaid shift to exviazyme/Nexviadyme. Thymoglobulin sales were €125 million and increased by 15.2%, reflecting increased sales in the US and in Rest of World.Praluent sales were €110 million and decreased by 6.8%, reflecting lower sales in Rest of World, specifically in China."

Sales • Aplastic Anemia • Familial Hypercholesterolemia • Hemophilia A • Hemophilia B • Pompe Disease • Type 2 Diabetes Mellitus

A Real-World Data Analysis of Alglucosidase Alfa in the FDA Adverse Event Reporting System (FAERS) Database. (PubMed, Drugs R D) - "There are many adverse events associated with the clinical use of alglucosidase alfa, which should be closely monitored in the FAERS database. As the most effective enzyme replacement therapy for Pompe disease, it is crucial to closely monitor these adverse events. Ensuring patient safety while balancing drug effectiveness is particularly important."

Adverse events • Journal • Real-world evidence • Infectious Disease • Inflammation • Pneumonia • Pompe Disease • Pulmonary Disease • Respiratory Diseases

Challenges in multinational rare disease clinical studies during COVID-19: regulatory assessment of cipaglucosidase alfa plus miglustat in adults with late-onset Pompe disease. (PubMed, J Neurol) - P3 | "PROPEL (ATB200-03; NCT03729362) compared the efficacy and safety of cipaglucosidase alfa plus miglustat (cipa + mig), a two-component therapy for late-onset Pompe disease (LOPD), versus alglucosidase alfa plus placebo (alg + pbo). Both statistical analysis approaches led to similar results and consistent conclusions, confirming the efficacy of cipa + mig for adults with LOPD. NCT03729362; trial start date: December 4, 2018.Trial registration number."

Journal • Infectious Disease • Lysosomal Storage Diseases • Metabolic Disorders • Novel Coronavirus Disease • Pompe Disease • Rare Diseases

Advances in Disease-Modifying Therapeutics for Chronic Neuromuscular Disorders. (PubMed, Semin Respir Crit Care Med) - "For myasthenia gravis (MG), efgartigimod, ravulizumab, rozanolixizumab, and zilucoplan have been Food and Drug Administration (FDA)-approved for the treatment of acetylcholine receptor (AChR) antibody-positive generalized MG in the past 2 years...For spinal muscular atrophy (SMA), nusinersen (intrathecal route) and risdiplam (oral route) modify the splicing of the SMN2 gene, increasing the production of normal survival motor neuron (SMN) protein...For late-onset Pompe disease (LOPD), avalglucosidase alfa has shown a greater improvement in respiratory function, ambulation, and functional outcomes in comparison to alglucosidase alfa, and cipaglucosidase alfa combined with miglustat has shown improvement in respiratory and motor function in a cohort of enzyme replacement therapy-experienced LOPD patients. Amyotrophic lateral sclerosis (ALS) remains a challenge. The two most recent FDA-approved medications, namely sodium phenylbutyrate and tofersen, may slow down the disease..."

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • Genetic Disorders • Movement Disorders • Myasthenia Gravis • Pompe Disease • Rare Diseases • SMN2

Study to Evaluate Efficacy and Safety in Chinese Patients with Late Onset Pompe Disease with One Year Alglucosidase Alfa Treatment (clinicaltrialsregister.eu) - P4 | N=40 | Sponsor: Genzyme

New P4 trial • Pompe Disease

Clinical modeling of motor function to predict treatment efficacy and enable in silico treatment comparisons in infantile-onset Pompe disease. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "Even with life-sustaining treatment (e.g., alglucosidase alfa [ALGLU]), many patients experience continued motor impairment. The Mini-COMET trial evaluated avalglucosidase alfa (AVAL) versus ALGLU on motor and other outcomes in IOPD...This study provides information on the relative efficacy of IOPD treatments and mitigates the confounding effects of imbalanced treatment cohorts. Our approach could also be applied in other rare diseases."

Journal • Pompe Disease • Rare Diseases

Importance of early treatment and quantitative evaluation of enzyme replacement therapy for Pompe disease: alglucosidase alfa post-marketing surveillance additional analysis (PubMed, Rinsho Shinkeigaku) - "The estimated slope of %FVC was significantly lower in the shorter group than in the longer group (P = 0.0051). These results suggest the importance of early treatment initiation and quantitative evaluation of each symptom."

Journal • P4 data • Metabolic Disorders • Pompe Disease

Switching treatment to cipaglucosidase alfa plus miglustat positively affects patient-reported outcome measures in patients with late-onset Pompe disease. (PubMed, J Patient Rep Outcomes) - P3 | "Overall, switching treatment from alglucosidase alfa to cipa+mig positively impacted PRO measurements during the double-blind period of PROPEL."

Clinical • Journal • Patient reported outcomes • CNS Disorders • Depression • Fatigue • Mood Disorders • Pompe Disease • Psychiatry

Hospital Costs of Pompe Disease in Patients With Myozyme: An Observational Study Based on the French National Hospital Discharge Database (PMSI) (ISPOR-EU 2024) - "The study generated robust real-world data to assess the hospital cost of Pompe disease in patients receiving myozyme®. With 4,195 stays in 2019 for 165 patients, the clinical burden induced by Pompe disease is considerable, but essential for patients."

Clinical • Observational data • Pompe Disease

Managed Entry Agreements to Mitigate Uncertainties and Reimbursement Challenges for Orphan Drugs: A Matrix to Determine Their Suitability (ISPOR-EU 2024) - "The selected case study of Myozyme® illustrated how the matrix can present stakeholders with additional suitable mitigation strategies for the relevant reimbursement challenges... To address reimbursement challenges for OMPs along their life cycle, it is valuable to consider both established and innovative, e.g., outcome-based MEAs. Combining reimbursement and payment models has the potential to effectively address multifaceted reimbursement challenges. The developed matrix fills a gap in providing systematic guidance for selecting MEAs tailored to OMPs, enhancing decision-making processes and ultimate patient access to OMPs targeting high unmet medical needs."

Reimbursement • US reimbursement

Indirect Treatment Comparison (ITC) of Avalglucosidase Alfa (AVA) vs Cipaglucosidase Alfa Plus Miglustat (Cipa+mig) in Late-Onset Pompe Disease (LOPD): An Updated Analysis Using Mixed-Model Repeated Measures (MMRM) Data (ISPOR-EU 2024) - P1, P1/2, P2, P3 | " The analysis of enzyme replacement therapy (ERT)-naïve patients used individual patient data (IPD) from the Phase 3 COMET trial (AVA, n =51; alglucosidase alfa, n =49) and aggregate data from the Phase 3 PROPEL trial (Cipa+mig, n =27). The analysis of ERT-experienced patients compared IPD from the COMET open-label extension and NEO-1 (NCT01898364)/NEO-EXT (NCT02032524) studies (AVA, n =59) vs aggregate data from the PROPEL and ATB200-02 (NCT02675465, Cohorts I and IV) studies (Cipa+mig, n =81)... Using the same MMRM analysis across different data sources, AVA demonstrated favorable respiratory function and mobility outcomes in patients with LOPD. The data are consistent and more favorable for AVA compared to the previous ITC analyses, with statistically significant results in treatment-naïve patients, and further support the comparative efficacy of AVA vs Cipa+mig."

Pompe Disease

Cipaglucosidase alfa plus miglustat: linking mechanism of action to clinical outcomes in late-onset Pompe disease. (PubMed, Front Neurol) - "First-generation recombinant human GAA (rhGAA) ERT (alglucosidase alfa) can slow the progressive muscle degeneration characteristic of the disease. Here, we investigate this hypothesis by analyzing published and new data related to the mechanism of action of the enzyme and stabilizer molecule. Based on an extensive collection of in vitro, preclinical, and clinical data, we conclude that cipaglucosidase alfa plus miglustat successfully addresses each of these challenges to offer meaningful advantages in terms of pharmacokinetic exposure, target-cell uptake, endolysosomal processing, and clinical benefit."

Clinical data • Journal • Lysosomal Storage Diseases • Metabolic Disorders • Pompe Disease • Rare Diseases

Late Onset Pompe Disease Masquerading as Chronic Hepatic Injury: A Case Report (ACG 2024) - "Early recognition of LOPD is paramount, as timely initiation of enzyme replacement therapy with Alglucosidase alfa can modify disease progression, improve clinical outcomes, and enhance quality of life...There are no significant plasma cells or eosinophils seen. The surrounding lobule shows mild sinusoidal dilation without significant steatosis or inflammatory activity."

Case report • Clinical • CNS Disorders • Dermatology • Fatigue • Hepatology • Hidradenitis Suppurativa • Immunology • Liver Failure • Myositis • Obesity • Pain • Pompe Disease • Psychiatry • Rheumatology • Schizophrenia

Pompe disease: Unmet needs and emerging therapies. (PubMed, Mol Genet Metab) - "The approval of avalglucosidase alfa (Nexviazyme®) and cipaglucosidase alfa (Pombiliti®) with miglustat (Opfolda®) represents a new generation of enzyme replacement therapies seeking to further improve patient outcomes beyond alglucosidase alfa. Key treatments include tissue-targeted enzyme replacement therapy, which seeks to enhance enzyme concentration in target tissues such as the central nervous system; substrate reduction therapy, which reduces intracellular glycogen concentrations via novel mechanisms; and gene therapy, which may restore endogenous production of deficient acid alpha-glucosidase. Each of these proposed treatments shows promise as a future therapeutic option to improve quality of life in Pompe disease by more efficiently treating the underlying cause of disease progression: glycogen accumulation."

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