Myozyme (alglucosidase alfa) / Sanofi - LARVOL DELTA

Enzyme replacement therapies in adults with Pompe disease: from trials to real-world data. (PubMed, Curr Opin Neurol) - "The advent of two next-generation enzyme replacement therapies marks a new era in treating patients diagnosed with Pompe disease. Clinical trials and early real-world data suggest that they may be superior to alglucosidase alfa, the standard of care for the past 20 years, although head-to-head comparisons between all three treatments are lacking. More data will become available over the next 5 years, leading to better guidelines for starting, stopping and switching therapies based on a more personalized assessment of outcomes."

Journal • Real-world evidence • Pompe Disease

The Mini-COMET Clinical Trial: Safety and Efficacy of Avalglucosidase Alfa after 97 Weeks of Treatment in Children with Infantile-Onset Pompe Disease Previously Treated with Alglucosidase Alfa. (PubMed, J Pediatr) - "Results support the positive clinical impact of long-term avalglucosidase alfa in children with IOPD."

Journal • CNS Disorders • Pompe Disease • Rare Diseases

Defining clinically meaningful thresholds for forced vital capacity in patients with neuromuscular disorders: Lessons learned from the COMET study in Pompe disease. (PubMed, J Neuromuscul Dis) - P3 | "Any improvement in FVC trajectory will delay ventilatory support; however, the change required for patients to perceive a noticeable clinical benefit, the clinically meaningful threshold (CMT), has not been defined in NMDs.ObjectiveTo derive the within-person and between-group CMTs for FVC (% predicted) in patients with late-onset Pompe disease (LOPD).MethodsThis analysis leverages data from the Phase 3 COMET trial (NCT02782741, registered 25 May 2016), which assessed the efficacy of avalglucosidase alfa (AVA) versus alglucosidase alfa (ALG) on upright FVC (% predicted) in LOPD. Post hoc application of these thresholds to COMET showed that a greater proportion of patients in the AVA group had clinically meaningful improvement in FVC versus ALG. These findings may aid in interpretation of data from studies in other NMDs."

Journal • CNS Disorders • Pompe Disease

A Prospective Study to Observe & Describe Clinical Outcomes of Alglucosidase Alfa Treatment in Patients ≤6 Months of Age With Infantile-onset Pompe Disease (IOPD) (clinicaltrials.gov) - P=N/A | N=16 | Active, not recruiting | Sponsor: Sanofi | Recruiting ➔ Active, not recruiting | Trial completion date: Mar 2026 ➔ Oct 2026 | Trial primary completion date: Mar 2026 ➔ Oct 2026

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

Switching Enzyme Replacement Therapy for Late-Onset Pompe Disease From Alglucosidase Alfa to Cipaglucosidase Alfa Plus Miglustat: Post Hoc Effect Size Analysis of PROPEL. (PubMed, Muscle Nerve) - P3 | "ERT-experienced patients with LOPD who switched from alg to cipa+mig treatment achieved improvements or stability in most outcomes."

Clinical • Journal • Retrospective data • Fatigue • Pompe Disease • Pulmonary Disease

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