Myozyme (alglucosidase alfa) / Sanofi - LARVOL DELTA

Focused ultrasound delivery of enzyme replacement therapy to the brain of Gaa-/- Pompe disease mice. (PubMed, Mol Genet Metab) - "We investigated GAA delivery and glycogen accumulation in 5-month-old Gaa-/- knockout mice following administration of two clinically available rhGAA ERTS (alglucosidase alfa and avalglucosidase alfa) at different dosages with and without FUS-BBB opening over four biweekly treatment sessions...Diphenhydramine was administered intraperitoneally 10 min before ERT to avoid anaphylactic response...Biochemical analysis supported these results, showing an increase in GAA enzyme activity and reduction in glycogen content for FUS + ERT treated mice compared to No FUS + ERT groups. Future work will determine if this promising treatment paradigm can rescue disease phenotypes that are downstream of glycogen accumulation and work towards clinical translation."

Journal • Preclinical • 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

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

Effects of combined therapy Ketogenic diet and alglucosidase alfa on Creatine Kinase Levels and motor outcome in Infantile Pompe Disease: Case Series (SSIEM 2023) - No abstract available

Clinical • Pompe Disease

Effects of Combine therapy Ketogenic diet and alglucosidase alfa on Creatine Kinase Levels and motor outcome in Infantile Pompe Disease: Case Series (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

Mini-COMET study: Safety and efficacy data after avalglucosidase alfa dosing for ≥145 weeks in patients with infantile-onset Pompe disease (IOPD) who had demonstrated clinical decline or sub-optimal response whilst receiving alglucosidase alfa (SSIEM 2023) - No abstract available

Clinical • Pompe Disease

Avalglucosidase alfa safety and immunogenicity profile in alglucosidase alfa-experienced participants with Pompe disease: Pooled analysis of clinical trial data (SSIEM 2023) - No abstract available

Retrospective data • 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

Effects of Combine therapy Ketogenic diet and alglucosidase alfa on Creatine Kinase Levels and motor outcome in Infantile Pompe Disease: Case Series (SSIEM 2023) - No abstract available

Clinical • Pompe Disease

Mini-COMET study: Safety and efficacy data after avalglucosidase alfa dosing for ≥145 weeks in patients with infantile-onset Pompe disease (IOPD) who had demonstrated clinical decline or sub-optimal response whilst receiving alglucosidase alfa (SSIEM 2023) - No abstract available

Clinical • Pompe Disease

Avalglucosidase alfa safety and immunogenicity profile in alglucosidase alfa-experienced participants with Pompe disease: Pooled analysis of clinical trial data (SSIEM 2023) - No abstract available

Retrospective data • Pompe Disease

Effects of Combine therapy Ketogenic diet and alglucosidase alfa on Creatine Kinase Levels and motor outcome in Infantile Pompe Disease: Case Series (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

Mini-COMET study: Safety and efficacy data after avalglucosidase alfa dosing for ≥145 weeks in patients with infantile-onset Pompe disease (IOPD) who had demonstrated clinical decline or sub-optimal response whilst receiving alglucosidase alfa (SSIEM 2023) - No abstract available

Clinical • Pompe Disease

Avalglucosidase alfa safety and immunogenicity profile in alglucosidase alfa-experienced participants with Pompe disease: Pooled analysis of clinical trial data (SSIEM 2023) - No abstract available

Retrospective data • 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) - P3 | "Patients switching to cipa+mig did not demonstrate any significant within-group worsening and showed significant improvements for 6-minute walk distance (absolute and % predicted); upper, lower and overall manual muscle test; PROMIS fatigue; physician and subject global impression of change (5 of 8 subdomains); CK and Hex4 levels. Conclusions This analysis shows that ERT-experienced patients with LOPD who switched from alg to cipa+mig treatment achieved improvements in a number of outcomes, highlighting the potential of cipa+mig to become an important treatment option for these patients."

Clinical • Fatigue • 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) - P3 | "No new safety signals were identified. Conclusions These data show that switching treatment from alg to cipa+mig was associated with a durable effect up to 104 weeks and was well tolerated, supporting long-term benefits of cipa+mig treatment for patients with LOPD."

Clinical • Fatigue • Pompe Disease

Effects of Combine therapy Ketogenic diet and alglucosidase alfa on Creatine Kinase Levels and motor outcome in Infantile Pompe Disease: Case Series (SSIEM 2023) - "Our results indicate that KD might have a favorable effect on muscle strength in PD."

Clinical • Pompe Disease

Mini-COMET study: Safety and efficacy data after avalglucosidase alfa dosing for ≥145 weeks in patients with infantile-onset Pompe disease (IOPD) who had demonstrated clinical decline or sub-optimal response whilst receiving alglucosidase alfa (SSIEM 2023) - P2 | "AVA ≤40mg/kg/qow was well-tolerated, with no safety risk seen in patients switched from ALG to AVA. The long-term data further support AVA’s durable impact in IOPD. Funding: Sanofi"

Clinical • Hypotension • Pompe Disease

Avalglucosidase alfa safety and immunogenicity profile in alglucosidase alfa-experienced participants with Pompe disease: Pooled analysis of clinical trial data (SSIEM 2023) - "This pooled analysis of alglucosidase alfa-experienced participants who switched to avalglucosidase alfa showed no significant immunologic concerns following the switch. This builds upon prior evidence showing that avalglucosidase alfa’s immunologic profile is improved versus alglucosidase alfa. Funded: Sanofi"

Retrospective data • Pompe Disease

Switching treatment from alglucosidase alfa to cipaglucosidase alfa plus miglustat positively affects motor function and quality of life in patients with late-onset Pompe disease (SSIEM 2023) - P3 | "The Phase III PROPEL trial (NCT03729362) assessed efficacy and safety of the enzyme- replacement therapy (ERT) cipaglucosidase alfa+miglustat (cipa+mig) versus alglucosidase alfa+placebo (alg+pbo) in adults with LOPD. Results Group-level analyses favored cipa+mig versus alg+pbo in the vast majority of motor function and PRO measures, with nominal significance for walking tests and SGIC’s ‘ability to move around’ and ‘energy level.’ Patient-level responder analyses showed a greater proportion of patients improved with cipa+mig versus alg+pbo for most PRO measures. Differences in proportions of responders between cipa+mig versus alg+pbo were nominally significant for SGIC’s ‘overall well-being,’ ‘ability to move around,’ ‘muscle function’ and ‘energy level.’ Conclusion These analyses highlight the patient perspective and provide evidence that switching from alg+pbo to cipa+mig benefits patients’ motor function and HRQoL."

Clinical • HEOR • Pompe Disease