Nexviazyme (avalglucosidase 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

A SHOCKING RESCUE: NOVEL USE OF ENZYME REPLACEMENT THERAPY FOR VENTRICULAR TACHYCARDIA IN LATE-ONSET POMPE DISEASE - Mohamad Sabra (ACC 2025) - "Enzyme replacement therapy (ERT) with avalglucosidase alfa was initiated seven days after presentation... Our case presents a unique application of ERT in late-onset Pompe disease for VT suppression."

Anesthesia • Cardiomyopathy • Cardiovascular • Pompe Disease • Ventricular Tachycardia

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

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 | Recruiting ➔ Active, not recruiting

Enrollment closed • Metabolic Disorders • Pediatrics • Pompe Disease

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

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: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Dec 2024 ➔ Dec 2025

Trial completion date • Trial primary completion date • Metabolic Disorders • 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) - "ALTUVIIIO (hemophilia A) sales were €230 million of which more than 85% were in the US...Nexviazyme/Nexviadyme (Pompe disease) sales were €184 million and increased by 42.0%, driven by Europe (+68.6%) and Rest of World (+55.0%). In the US (+26.3%)...Rezurock (chronic graft-versus-host disease) sales were €132 million and increased by 53.5%, driven by the US (+43.4%) and by launches in Europe (sales of €8 million) and in Rest of World (sales of €5 million)...Cablivi (acquired thrombotic thrombocytopenic purpura) sales were €73 million and increased by 24.1%, driven by an increased number of patients being identified for appropriate treatment, in the US and from launches in Europe and in Rest of World...Eloctate sales were €81 million and decreased by 21.4%, mainly due to patients converting to ALTUVIIIO in the US and in Japan. Aubagio sales were €78 million and decreased by 35.5%..."

Sales • Chronic Graft versus Host Disease • Hemophilia A • Multiple Sclerosis • Pompe Disease • Thrombocytopenic Purpura

Efficacy and safety of avalglucosidase alfa in Japanese patients with late-onset and infantile-onset Pompe diseases: A case series from clinical trials. (PubMed, Mol Genet Metab Rep) - "Importantly, avalglucosidase alfa was well tolerated at doses of both 20 mg/kg and 40 mg/kg in Japanese patients with LOPD and IOPD, respectively. Although the number of patients was small, avalglucosidase alfa provides an efficacy and safety profile in Japanese patients representative of the overall populations from key global clinical trials."

Journal • 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=18 | Recruiting | Sponsor: Sanofi | Trial completion date: Aug 2026 ➔ Aug 2027 | Trial primary completion date: Dec 2024 ➔ Feb 2026

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

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

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

Quantitative Systems Pharmacology-Based Digital Twins Approach Supplements Clinical Trial Data for Enzyme Replacement Therapies in Pompe Disease. (PubMed, Clin Pharmacol Ther) - "The digital twin analysis supports the interpretation that the enhanced reduction in urine Hex4 observed following avalglucosidase alfa treatment is attributable to greater tissue glycogen clearance. Overall, this study provides mechanism-based insight into avalglucosidase alfa efficacy across the phenotypic spectrum of Pompe disease and demonstrates the value of applying a QSP-based digital twin analysis to support rare disease drug development."

Journal • CNS Disorders • Pompe Disease • Rare Diseases

Home infusion experience in patients with Pompe disease receiving avalglucosidase alfa during three clinical trials. (PubMed, Mol Genet Metab) - "These data suggest that infusion of avalglucosidase alfa at home is feasible and does not compromise safety for patients who have not experienced an infusion-associated reaction during the preceding 12 months of infusions in a clinical setting. Evaluation of real-world experience with avalglucosidase alfa home infusion in countries where it is already approved is ongoing."

Journal • Pompe Disease

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

China Post-approval Commitment (PAC) Study of Avalglucosidase Alfa in Participants With IOPD (clinicaltrials.gov) - P4 | N=13 | Not yet recruiting | Sponsor: Genzyme, a Sanofi Company

New P4 trial • Metabolic Disorders • Pompe Disease

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

Muscle and Nerve Biopsy – Do We Still Need it in the Era of Ngs? (ICNMD 2024) - "Since 2006 Enzyme Replacement Therapy (ERT) has been available, several trials in GSD2 with various types of Neo-GAA and chaperones have been done as well as trials with Next Generation ERT...Many rhabdomyolytic episodes are not predictable, making biopsy evaluation useful to demonstrate its pathology (Figure illustrates necrotic myofibers invaded by macrophages), likewise in colchicine or statin myopathies...A biopsy might be required in amyloid neuropathies and familial ATTR amyloid polyneuropathy, currently becoming a treatable disease. Nerve biopsy in diseases such as pure neuritic leprosy, neurosarcoidosis, and neurolymphomatosis enables a definitive diagnosis."

Biopsy • Next-generation sequencing • Amyloidosis • CNS Disorders • Complement-mediated Rare Disorders • Hematological Malignancies • Immunology • Lymphoma • Melanoma • Metabolic Disorders • Muscular Dystrophy • Myositis • Oncology • Pain • Pompe Disease • Sarcoidosis • Solid Tumor

Comparing the efficacy of cipaglucosidase alfa plus miglustat with other enzyme replacement therapies for late-onset Pompe disease: a network meta-analysis utilizing patient-level and aggregate data. (PubMed, J Comp Eff Res) - "Until recently, standard of care was enzyme replacement therapy (ERT) with alglucosidase alfa. Second-generation ERTs avalglucosidase alfa (aval) and cipaglucosidase alfa with miglustat (cipa+mig) are now available...Analysis of network A showed that cipa+mig was associated with a relative decrease in 6MWD (-10.02 m [-23.62 to 4.00 m]; 91.8%) and FVC (-1.45 pp [-3.01 to 0.07 pp]; 96.8%) compared with aval. Cipa+mig showed a favorable effect versus aval when all available evidence was used in the analysis."

Journal • Retrospective data • Pompe Disease

Optimizing clinical outcomes: The journey of twins with CRIM-negative infantile-onset Pompe disease on high-dose enzyme replacement therapy and immunomodulation. (PubMed, Mol Genet Metab Rep) - "Both twins received immune tolerance induction (ITI) with rituximab, methotrexate, and IVIG to mitigate antibody response. These cases underscore the importance of early, high-dose ERT combined with ITI in managing CRIM-negative IOPD. While transitioning to avalglucosidase-alfa at 40 mg/kg/EOW was beneficial and well-tolerated in our patients, further studies are needed to confirm its long-term efficacy compared to the high-dose weekly 40 mg/kg alglucosidase-alfa."

Clinical data • Immunomodulating • Journal • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Immunology • Pompe Disease

Mini-COMET: A Study to Assess Safety and Efficacy of Avalglucosidase Alfa Administered Every Other Week in Pediatric Patients With Infantile-onset Pompe Disease Previously Treated With Alglucosidase Alfa (clinicaltrials.gov) - P2 | N=22 | Active, not recruiting | Sponsor: Genzyme, a Sanofi Company | Trial completion date: Jun 2026 ➔ Dec 2026

Trial completion date • Metabolic Disorders • Pediatrics • Pompe Disease

EXPLORING THE THERAPEUTIC POTENTIAL OF AVALGLUCOSIDASE ALFA IN INFANTILE-ONSET POMPE DISEASE WITH HIGH ANTI-ALGLUCOSIDASE ALFA ANTIBODY TITERS (SSIEM 2024) - "This case marks the first real-world use of neoGAA for IOPA patients outside Mini-COMET. Our patient tolerated it well, experiencing improved motor and respiratory function without allergic reactions. Long-term monitoring for allergic reactions and antibody titers is crucial."

Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Lysosomal Storage Diseases • Metabolic Disorders • Pompe Disease • Pulmonary Disease • Rare Diseases

MODELLING AND INTEGRATED IN SILICO TRIAL SIMULATION: HEAD-TO-HEAD MOTOR COMPARISON OF AVALGLUCOSIDASE ALFA AND ALGLUCOSIDASE ALFA IN INFANTILE-ONSET POMPE DISEASE (SSIEM 2024) - P2, P3 | "Our integrated modelling and in silico clinical trial simulation scenarios successfully showed motor improvement for AVA vs ALG in patients with IOPD."

Head-to-Head • Pompe Disease

CHARACTERISTICS OF PATIENTS WITH INFANTILE-ONSET POMPE DISEASE WHO SWITCHED TREATMENTS FROM ALGLUCOSIDASE ALFA TO AVALGLUCOSIDASE ALFA: BASELINE POMPE REGISTRY DATA (SSIEM 2024) - P | "Real-world data shows that patients with IOPD are switching from ALG to AVA, the majority being on a higher/more frequent dose of ALG at the time of switch and commencing AVA at 40 mg/kg qow. As more patients enrol in the Registry and switch from ALG to AVA, our understanding of AVA's effectiveness over time will be enhanced."

Clinical • Pompe Disease