Vimizim (elosulfase alfa) / BioMarin - LARVOL DELTA

Enhancing Enzyme Replacement Therapy in Lysosomal Storage Disorders: Faster Infusion Rates Across the UK (SSIEM 2026) - "Frequently accelerated treatments included agalsidase beta, alglucosidase alfa, avalglucosidase alfa, cipaglucosidase alfa with miglustat, laronidase, elosulfase, idursulfase, and galsulfase. Accelerated ERT infusion rates outside SmPC recommendations are already in widespread use across UK LSD centres without evidence of elevated infusion-related adverse events. While practice varies, centres successfully shorten treatment duration by modifying infusion protocols. Wider sharing of local protocols and outcomes may improve equity for patients across centres, reduce treatment burden and shorter nursing homecare visits which in turn will reduce financial burden to the NHS."

Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Early versus Late Enzyme Replacement Therapy for Korean Siblings with Morquio A: a Longitudinal Study (SSIEM 2026) - "Early initiation of ERT with elosulfase alfa appears to attenuate severe spinal and upper-body manifestations in MPS IVA but does not prevent progression of lower-limb skeletal disease. Thesefindings underscore the importance of early therapeutic intervention combined with ongoingorthopedic management to preserve cardiorespiratory function and overall physical capacity."

Longitudinal study • Observational data • Cardiovascular • Lysosomal Storage Diseases • Metabolic Disorders • Musculoskeletal Diseases • Orthopedics • Rare Diseases

Early Versus Late Enzyme Replacement Therapy in Siblings With Morquio A Syndrome: Insights Into Therapeutic Timing. (PubMed, JIMD Rep) - "Enzyme replacement therapy (ERT) with elosulfase alfa is the only approved treatment for mucopolysaccharidosis type IVA...Cardiorespiratory assessment revealed normalized left ventricular mass index z-scores, stable ejection fractions, and the absence of valvular pathology. Overall, these findings suggest that early ERT attenuates severe spinal and upper body manifestations but does not prevent lower limb skeletal progression, highlighting the need for early therapeutic initiation along with orthopedic intervention to preserve cardiorespiratory parameters and functional independence."

Journal • Musculoskeletal Diseases • Orthopedics

Long-term follow-up and response to elosulfase alfa in mucopolysaccharidosis type IVA: a single-center cohort from the Czech Republic. (PubMed, Orphanet J Rare Dis) - "Documenting the natural history of MPS IVA in this population may aid early diagnosis. Despite the disease's progressive nature, ERT led to stabilization of monitored parameters in treated children."

Journal • Dermatology • Hidradenitis Suppurativa • Immunology • Lysosomal Storage Diseases • Metabolic Disorders • Musculoskeletal Diseases • Orthopedics • Rare Diseases

Growth Patterns in MPS IVA and MPS IIIA: A Longitudinal Single-Center Study. (PubMed, J Clin Med) - " ERT with Elosulfase alfa did not prevent progressive height loss relative to population norms. The rate of height SDS decline was not significantly influenced by the timing of ERT initiation (interaction p = 0.53), and causal conclusions cannot be drawn from this observational data."

Journal • Lysosomal Storage Diseases • Metabolic Disorders • Obesity • Orthopedics • Rare Diseases

Long-term Natural History and Elosulfase Alfa Treatment for Mucopolysaccharidosis Type IVA: A Single-Center Study in the Czech Republic. (PubMed, Res Sq) - " Documenting the natural history of MPS IVA in this population may aid in early diagnosis. Despite the disease's progressive nature, ERT was effective in our MPS IVA patients, demonstrating a consistent impact on endurance across all age groups."

Journal • Dermatology • Hidradenitis Suppurativa • Immunology • Lysosomal Storage Diseases • Metabolic Disorders • Orthopedics • Rare Diseases

Phenotypes of Elosulfase Alfa-Induced Immediate Hypersensitivity Reactions and Long-term Outcomes of Desensitization in Mucopolysaccharidosis IVA. (PubMed, Int Arch Allergy Immunol) - "ELA-induced I-HSRs are relatively frequent in MPS IVA, occur predominantly as Type I phenotypes, and are clinically significant. Younger age at diagnosis (≤30 months) markedly increases the risk of I-HSRs, and RDD is safe and effective long-term."

Journal • Immunology • Inflammation • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Long-term follow-up of attenuated forms of MPS IVA: benefit of enzyme replacement therapy and contribution of quantitative gait analysis. (HMGC 2026) - "Since 2014, enzyme replacement therapy with elosulfase alfa (VIMIZIM®) has been approved for marketing in France...However, the comprehensive and time-consuming MorCAP protocol could not be fully implemented despite the support of a coordinating nurse. The data from this study could contribute to the development of individualized recommendations aimed at strengthening adherence to treatment and adapting follow-up strategies to the specific needs of patients with MPS IVA, particularly attenuated forms."

Lysosomal Storage Diseases • Metabolic Disorders • Orthopedics • Rare Diseases • Rheumatology

Clinical expert opinion on the role of elosulfase alfa in non-ambulatory individuals with Morquio A syndrome. (PubMed, Mol Genet Metab Rep) - "This explorative study offers valuable insights into drivers of ERT use in non-ambulatory patients with Morquio A, its potential benefits, and strategies for monitoring treatment outcomes in clinical practice. These findings may guide patient management, optimize treatment, and inform future research for this population."

Journal • Pain

Role of Real-World Evidence (RWE) in Pricing and Reimbursement Decisions for Rare Disease in Health Technology Assessment (HTA) Submissions Across EU4 + UK (ISPOR-EU 2025) - "Onasemnogene abeparvovec and Elosulfase alfa were reimbursed in all five markets... HTA bodies have primarily accepted RWE to provide external comparators or to supplement clinical effectiveness data in rare disease therapies, though acceptance remains variable across agencies and may become more standardized under the EU Joint Clinical Assessment (EU-JCA)."

Clinical • HEOR • Pricing • Real-world • Real-world evidence • Reimbursement • US reimbursement • CNS Disorders • Gene Therapies • Rare Diseases

Association of Elosulfase Alpha for Quality of Life In Morquio IV-A Syndrome: A Case Series (SSIEM 2023) - No abstract available

Clinical • HEOR

Long-term outcomes of elosulfase alfa enzyme replacement therapy in adults with MPS IVA: a sub-analysis of the Morquio A Registry Study (MARS). (PubMed, Orphanet J Rare Dis) - "Real-world data collected from MARS suggest that patients with MPS IVA who initiated ERT in adulthood remained stable over 7 years of follow-up. No new safety signals were identified."

Journal • Rare Diseases

Recent advances in mucopolysaccharidosis IVA treatment. (PubMed, Orphanet J Rare Dis) - "Although enzyme replacement therapy (ERT) with elosulfase alfa is currently the only approved treatment, its clinical benefit on bone pathology is limited due to rapid clearance and poor penetration into avascular cartilage. Strategies to enhance enzyme stability and targeting, such as PEGylated hydrogels and extracellular vesicles, have shown promise in enhancing the biodistribution and stability of GALNS, while pharmacological chaperones, including ezetimibe, pranlukast, and bromocriptine, seem to stabilize GALNS in vitro...Importantly, recent evidence revealed that mitochondrial dysfunction in chondrocytes may contribute to the pathology of MPS IVA, uncovering new targets beyond GALNS enzyme activity recovery. This review highlights recent advances in the treatment of MPS IVA and discusses new directions to improve outcomes in MPS IVA treatment."

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

Natural History of Atypical Morquio A Disease (clinicaltrials.gov) - P=N/A | N=7 | Completed | Sponsor: GOIZET | Recruiting ➔ Completed | N=10 ➔ 7 | Trial completion date: Jul 2027 ➔ Sep 2025

Enrollment change • Trial completion • Trial completion date

Real-world treatment with elosulfase alfa in patients with MPS IVA is associated with improved endurance over time. (PubMed, Genet Med Open) - "Standing height was also associated with longer 6MWT in the multivariate quantile analysis, except in participants aged 5 to <7 years. This analysis assessed associations between ERT exposure and endurance to confirm the real-world, long-term effectiveness of elosulfase alfa in participants with MPS IVA."

HEOR • Journal • Real-world evidence

Exploring Multivalent Architectures for Binding and Stabilization of N-Acetylgalactosamine 6-Sulfatase. (PubMed, Molecules) - "Currently, enzyme replacement therapy (ERT) is used to treat Morquio A through the infusion of the recombinant enzyme VIMIZIM® (elosulfase alfa, BioMarin)...We report in this work the synthesis of a library of multivalent glycomimetics exploiting the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction between several dendrimeric scaffolds armed with terminal alkynes and azido ending iminosugars of different structures (pyrrolidines, piperidines, and pyrrolizidines) or simple azido ending carbohydrates as bioactive units. The biological evaluation identified pyrrolidine-based nonavalent dendrimers 1 and 36 as the most promising compounds, able both to bind the native enzyme with IC50 in the micromolar range and to act as enzyme stabilizers toward rhGALNS in a thermal denaturation study, thus identifying promising compounds for a combined PC/ERT therapy."

Journal

Efficacy of different treatment strategies in patients with mucopolysaccharidosis: a systematic review and network meta-analysis of randomized controlled trials. (PubMed, Orphanet J Rare Dis) - "In MPS IV, 6-min walking test (6MWT) (40.82, 95% CI[16.19, 64.92]) and 3-min stair climb test (3MSCT) (16.07, 95% CI[12.16, 21.62]) were significantly increased in patients who took elosulfase alfa at a dose of 4.0 mg/kg/week compared with the placebo group. In MPS VI, recombinant human arylsulfatase B (rhASB) and galsulfase (1.0 mg/kg/week) significantly reduced uGAG aggregation compared with the placebo group (-217, 95% CI[-258, -176]) and galsulfase (2.0 mg/kg/week) group (-286.5, 95% CI[-436.5, -136.5]), respectively...ERT alleviated symptoms to some extent, but current evidence was insufficient. Hence, further evidence from large-sample RCT is needed."

Journal • Retrospective data • Review

Long-term outcomes of enzyme replacement therapy from a large cohort of Korean patients with mucopolysaccharidosis IVA (Morquio A syndrome). (PubMed, Mol Genet Metab Rep) - "At follow-up, patients experienced improvements in functional independence measure score, ejection fraction, and the 6-min walk test compared with the pre-treatment baseline. This study provides real-world evidence for long-term stabilization of functional independence, endurance, and respiratory function among patients with MPS IVA treated with ERT, with no new safety concerns identified."

Journal • Dermatology • Hurler Syndrome • Immunology • Lysosomal Storage Diseases • Metabolic Disorders • Pain • Rare Diseases • Urticaria

The Impact of Weight-Based Dosing on Pricing and Reimbursement Outcomes for Ultra-Rare Disease Treatments in the EU4 (ISPOR-EU 2024) - "All 7 drugs were reimbursed in all EU4 markets, except for vestronidase alfa in France and elosulfase alfa, asfotase alfa, velmanase alfa and olipudase alfa in Spain where these treatments were not recommended for reimbursement. Although most treatments were reimbursed in all markets at a relatively high list price, it is likely that significant confidential discounts would have been required, as suggested by price reductions following negotiations in Germany. The high number of treatments not recommended for reimbursement in Spain suggests payer uncertainty due to high costs and weight-based dosing in this budget-focused market. It is important for payers and manufacturers to work together to manage the uncertainty of weight-based dosing to reach an agreement that satisfies all stakeholders and enables access for patients in need."

Pricing • Reimbursement • US reimbursement • Pediatrics • Rare Diseases

Cost of Treatment for Mucopolysaccharidosis IV-A in a Poor Population in Colombia (ISPOR-EU 2024) - "Elosulfase Alfa IV was the main and most expensive treatment consumed by these patients... This study provides strategic information for the planning of health care strategies. Extrapolating the costs to the prevalence of the disease in Colombia could estimate the economic burden and its impact on the Colombian health system. The use of enzyme replacement therapy (ERT) contributes to cost reduction by minimizing the risk of bone, respiratory, infectious, ear/hearing, cardiovascular, dental, and ophthalmological complications that deteriorate the quality of life of patients."

Clinical • HEOR • Treatment costs • Cardiovascular • Genetic Disorders • Ophthalmology

FOUR SIBLINGS WITH MUCOPOLYSACCHARIDOSIS TYPE IV A RECEIVING ENZYME REPLACEMENT THERAPY: IMPACT OF CONSANGUINITY (SSIEM 2024) - "Lysosomal storage disease was suspected clinically, and the diagnosis was confirmed by whole exome sequence showing homozygous pathogenic mutation in the GALNS gene and was accordingly started on ERT, Elosulfase Alfa...Given the disease's mode of inheritance, this family reflects the effects of increased consanguinity rate among Saudi population, therefore we recommend to add MPS IVA to premarital screening for families at risk. Palavras-chave : Mucopolysaccharidosis, Consanguinity, Enzyme Replacement Therapy (ERT)"

Hurler Syndrome • Lysosomal Storage Diseases • Metabolic Disorders • Musculoskeletal Diseases • Orthopedics • Rare Diseases

MUCOPOLYSACCHARIDOSES IN ADULT PATIENTS – ONE CENTRE EXPERIENCE (SSIEM 2024) - "ERT depended on the MPS`s type and included laronidase, idursulfase, elosulfase alfa, and galsulfase. Our patients treated with ERT have good compliance and almost no significant progression of their diseases in ten-year follow-up."

Clinical • Alzheimer's Disease • Atrial Fibrillation • Cardiovascular • Cognitive Disorders • Hurler Syndrome • Infectious Disease • Lysosomal Storage Diseases • Metabolic Disorders • Musculoskeletal Diseases • Rare Diseases • Respiratory Diseases

LONG-TERM OUTCOME OF ENZYME REPLACEMENT THERAPY FROM A LARGE COHORT OF KOREAN PATIENTS WITH MUCOPOLYSACCHARIDOSIS IVA (MORQUIO A SYNDROME) (SSIEM 2024) - "We report the long-term outcome of elosulfase alfa enzyme replacement therapy (ERT) as well as clinical and genetic features in Korean patients with MPS IVA... This is a long-term observational study of Korean MPS IVA patients in one single center. We provide real-world evidence for long-term stabilization of functional independence, endurance, and respiratory function among ERT-treated patients, with no new safety concerns identified."

Clinical • Lysosomal Storage Diseases • Metabolic Disorders • Orthopedics • Rare Diseases

Potential Targeting Mechanisms for Bone-Directed Therapies. (PubMed, Int J Mol Sci) - "Although direct recombinant enzymes (e.g., Vimizim for Morquio, Cerezyme for Gaucher, Elaprase for Hunter, Mepsevii for Sly diseases) or hormone infusions (estrogen for osteoporosis and osteoarthritis), traditional gene delivery (e.g., direct infusion of viral or non-viral vectors with no modifications on capsid, envelope, or nanoparticles), and cell therapy strategies (healthy bone marrow or hematopoietic stem cell transplantation) partially improve bone lesions, novel delivery methods must be addressed regarding target specificity, less immunogenicity, and duration in circulation. Targeted drug delivery using organic and inorganic compounds is a promising approach in mostly preclinical settings and future clinical translation. This review comprehensively summarizes the current bone-targeting strategies based on bone structure and remodeling concepts while emphasizing potential approaches for future bone-targeting systems."

Journal • Review • Bone Marrow Transplantation • Immunology • Osteoarthritis • Osteoporosis • Pain • Rheumatology • Transplantation

A Multicenter, Multinational, Observational Morquio A Registry Study (MARS) (clinicaltrials.gov) - P=N/A | N=418 | Completed | Sponsor: BioMarin Pharmaceutical | Active, not recruiting ➔ Completed | Trial completion date: Sep 2024 ➔ Feb 2024 | Trial primary completion date: Sep 2024 ➔ Feb 2024

Trial completion • Trial completion date • Trial primary completion date