Nexviazyme (avalglucosidase 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

When the Diaphragm Fails: Visual Hallucinations Due to Isolated Respiratory Muscle Weakness as a First Manifestation of Late-Onset Pompe Disease. (PubMed, Eur J Case Rep Intern Med) - "Isolated respiratory failure due to diaphragm weakness can be the first manifestation of late-onset Pompe disease.Diagnosing diaphragmatic weakness is challenging in cardiopulmonary disease, as symptoms may be misattributed.Visual hallucinations are a rare symptom of nocturnal hypoventilation."

Journal • Cardiovascular • Congestive Heart Failure • Critical care • Heart Failure • Metabolic Disorders • Pompe Disease • Pulmonary Disease • Respiratory Diseases

Real-world data: switching to avalglucosidase alfa and exploring the impact of home-infusion on the quality of life of patients with late-onset Pompe disease (SSIEM 2023) - "Sponsored by Sanofi"

Clinical • HEOR • Real-world • Real-world evidence • Pompe Disease

A cohort summary: switching to avalglucosidase alfa in patients with infantile-onsetand late-onset disease (SSIEM 2023) - "Sponsored by Sanofi"

Clinical • Pompe Disease

Efficacy and safety of avalglucosidase alfa in participants with late-onset Pompedisease after 145 weeks’ treatment during the COMET trial (SSIEM 2023) - "Sponsored by Sanofi"

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

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

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

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

Addressing the needs of patients with Pompe disease – translating clinical trial data into real-world practice (SSIEM 2023) - "To share the current evidence related to avalglucosidase alfa as an alternativetherapy option for patients with Pompe disease2. To discuss how patients, in real-world settings, are responding toavalglucosidase alfa"

Clinical • Real-world • Real-world evidence • Pompe Disease

Hypertrophic cardiomyopathy in Pompe disease following avalglucosidase alfa therapy. (PubMed, An Pediatr (Engl Ed)) - No abstract available

Journal • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • 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 2025 ➔ Sep 2026 | Trial primary completion date: Dec 2025 ➔ Sep 2026

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

An Indirect Treatment Comparison of Avalglucosidase Alfa versus Cipaglucosidase Alfa Plus Miglustat in Patients with Late-Onset Pompe Disease. (PubMed, Adv Ther) - P1, P1/2, P2, P3 | "ITCs suggest more favourable respiratory and mobility outcomes with AVA versus Cipa+mig in patients with LOPD, regardless of prior ERT-experience."

Journal • Pompe Disease

Marked Improvements in Airway Abnormalities and Multifaceted Outcomes After 2 Years Switching to Avalglucosidase Alfa: Evaluation of A 19-Year-Old Male Diagnosed With Late-Onset Pompe Disease. (PubMed, Am J Med Genet A) - "The primary GAA deficiency treatment is enzyme replacement therapy (ERT) with alglucosidase alfa; however, its long-term efficacy seems to diminish with time. The therapy switch improved airway abnormalities, as demonstrated by flexible bronchoscopy in polysomnography results, activity endurance, core muscle strength, body mass index, and disease-specific biomarkers, including creatine kinase, aspartate transaminase, and urinary glucose tetrasaccharide (Glc4) levels. This study highlights the potential benefits of avalglucosidase alfa in managing respiratory outcomes in patients with late-onset PD, suggesting its promising effects for long-term treatment."

Journal • Metabolic Disorders • Myositis • Pompe Disease • Respiratory Diseases

Efficacy of avalglucosidase alfa in infantile-onset Pompe disease with high anti-alglucosidase alfa antibody titers. (PubMed, Pediatr Int) - No abstract available

Journal • Pompe Disease

Enzyme replacement therapy for the treatment of late onset Pompe disease: A systematic review and network meta-analysis. (PubMed, Orphanet J Rare Dis) - "Our NMA results showed that ERTs lead to modest improvements in 6MWD after 1 year compared to placebo in ERT-naive populations. However, there is limited evidence supporting meaningful differences in outcomes between ERTs. There is a lack of longer-term follow-up data supporting the effectiveness of ERTs compared to each other and to best supportive care."

Clinical • Journal • Retrospective data • Review • Metabolic Disorders • Pompe Disease

Efficacy and safety of avalglucosidase alfa in patients with late-onset Pompe disease after 145 weeks of treatment during the COMET trial. (PubMed, J Neurol) - P3 | "In this randomized clinical trial extension, positive clinical outcomes were maintained for patients taking avalglucosidase alfa for up to 145 weeks with no new safety concerns."

Clinical • Journal • Pompe Disease

Efficacy of Switching Therapy From Alglucosidase Alfa to Avalglucosidase Alfa on Respiratory Function in Participants With Late-Onset Pompe Disease: A Post Hoc Analysis From the COMET Trial. (PubMed, JIMD Rep) - P3 | "Similar results were observed using ΔFVC ≥ 3% predicted as a measure of clinically meaningful change. This analysis demonstrates clinically meaningful maintenance in measures of lung volume (FVC) and airflow (forced expiratory volume in 1 s) after switching therapy from ALG to AVA that persists for ≥ 2 years and is independent of prior outcomes with ALG."

Journal • Retrospective data • CNS Disorders • Pompe Disease

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

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

Enrollment open • Metabolic Disorders • Pompe Disease