Mepsevii (vestronidase alfa) / Ultragenyx, Amicus - LARVOL DELTA

Vestronidase Alfa for the treatment of mucopolysaccharidosis VII (MPS VII): Updated results from a novel, longitudinal, multicenter disease monitoring program (DMP) (SSIEM 2023) - No abstract available

Clinical • Hunter Syndrome

Vestronidase Alfa for the treatment of mucopolysaccharidosis VII (MPS VII): Updated results from a novel, longitudinal, multicenter disease monitoring program (DMP) (SSIEM 2023) - No abstract available

Clinical • Hunter Syndrome

Vestronidase Alfa for the treatment of mucopolysaccharidosis VII (MPS VII): Updated results from a novel, longitudinal, multicenter disease monitoring program (DMP) (SSIEM 2023) - No abstract available

Clinical • Hunter Syndrome

Vestronidase Alfa for the treatment of mucopolysaccharidosis VII (MPS VII): Updated results from a novel, longitudinal, multicenter disease monitoring program (DMP) (SSIEM 2023) - "The benefit-risk profile of vestronidase alfa continues to be unchanged and favorable for use in pediatric and adult patients with MPS VII. Reductions in dermatan sulfate demonstrate effectiveness to at least Month 24 and clinical parameters are stable. Enrollment is ongoing, and patients continue to be assessed."

Clinical • Cough • Hunter Syndrome • Lysosomal Storage Diseases • Metabolic Disorders • Pediatrics • Rare Diseases • Respiratory Diseases

Enzyme Replacement Therapy in Mucopolysaccharidosis Type VII: A Three-Year Clinical Outcome Study of the First Taiwanese Case. (PubMed, Diagnostics (Basel)) - "ERT with vestronidase alfa was initiated at age 6... This case demonstrates the effectiveness and safety of long-term ERT in MPS VII, particularly in improving respiratory function and physical performance. Our experience highlights the importance of early diagnosis and treatment initiation, while providing valuable insights into the management of this ultrarare disease in the Asian population."

Clinical data • Journal • Developmental Disorders • Hunter Syndrome • Lysosomal Storage Diseases • Metabolic Disorders • Orthopedics • Rare Diseases

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

EVALUATING CHANGES IN CLINICAL OUTCOMES IN MPS VII: RESULTS FROM THE MPS VII DISEASE MONITORING PROGRAM (DMP) (SSIEM 2024) - "Vestronidase alfa (VA; recombinant human GUS) enzyme replacement therapy is approved in multiple global regions for MPS VII... Findings show the heterogeneity of clinical presentation and further advance our understanding of the potential impact of treatment with VA upon natural history of MPS VII. The benefit-risk profile of VA remains favorable for children and adults with MPS VII."

Clinical • Clinical data • Fatigue • Lysosomal Storage Diseases • Metabolic Disorders • 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

Disease characteristics, effectiveness, and safety of vestronidase alfa for the treatment of patients with mucopolysaccharidosis VII in a novel, longitudinal, multicenter disease monitoring program. (PubMed, Orphanet J Rare Dis) - "To date, the DMP has collected invaluable MPS VII disease characteristic data. The benefit-risk profile of vestronidase alfa remains unchanged and favorable for its use in the treatment of pediatric and adult patients with MPS VII. Reductions in DS and CS uGAG demonstrate effectiveness of vestronidase alfa to Month 24. Enrollment is ongoing."

Journal • Hunter Syndrome • Lysosomal Storage Diseases • Metabolic Disorders • Pediatrics • Rare Diseases

Early clinical response and continued safety with vestronidase ALFA for the treatment of mucopolysaccharidosis VII (MPS VII) (SIMD 2024) - "These results support the heterogeneity of clinical presentation and contribute to the understanding of the natural history of MPS VII. The benefit-risk profile of vestronidase alfa continues to be favorable for use in pediatric and adult patients with MPS VII. Enrollment is ongoing, and patients continue to be assessed."

Clinical • Alzheimer's Disease • Cognitive Disorders • Fatigue • Hunter Syndrome • Lysosomal Storage Diseases • Metabolic Disorders • Orthopedics • Pediatrics • Rare Diseases • Respiratory Diseases

Vestronidase Alfa for the treatment of mucopolysaccharidosis VII (MPS VII): Updated results from a longitudinal, multicenter disease monitoring program (DMP) (ACMG 2024) - "The benefit-risk profile of vestronidase alfa continues to be unchanged and favorable for use in pediatric and adult patients with MPS VII. Reductions in dermatan sulfate demonstrate effectiveness to at least Month 24. Clinical parameters were stable over time and improved for some groups."

Clinical • Alzheimer's Disease • Cognitive Disorders • Cough • Hunter Syndrome • Lysosomal Storage Diseases • Metabolic Disorders • Orthopedics • Pediatrics • Rare Diseases • Respiratory Diseases

Mucopolysaccharidosis type VII (Sly syndrome) - What do we know? (PubMed, Mol Genet Metab) - "Current treatments include hematopoietic stem cell transplantation and enzyme replacement therapy with vestronidase alfa. Care should be individualized for each patient. Development of consensus guidelines for MPS VII management and treatment is needed, as consolidation of expert knowledge and experience (for example, through the MPS VII Disease Monitoring Program) may provide a significant positive impact to patients."

Journal • Review • Alzheimer's Disease • Bone Marrow Transplantation • Cognitive Disorders • Hunter Syndrome • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases • Transplantation

Lifetime Cost of Orphan Therapies in Paediatric Indications in Europe (ISPOR-EU 2023) - " Eleven therapies were identified: burosumab, cannabidiol, chenodeoxycholic acid, cerliponase alfa, dinutuximab beta, glibenclamide, metreleptin, nusinersen, tisagenlecleucel, velmanase alfa, and vestronidase alfa. Lifetime treatment costs in Europe vary up to 50-fold between therapies and 2-fold between countries. Treatment duration is a major contributor to the estimate. Our results are in line with previous findings that the clinical benefit is not associated with the lifetime cost and that potentially curative therapies offer a good value to payers."

Pediatrics

Exploring the feasibility of using the ICER Evidence Rating Matrix for Comparative Clinical Effectiveness in assessing treatment benefit and certainty in the clinical evidence on orphan therapies for paediatric indications. (PubMed, Orphanet J Rare Dis) - "Using the ICER Matrix to grade orphan therapies according to their treatment benefit and certainty is feasible. However, the assessment involves subjective judgements based on heterogenous evidence. Tools such as the ICER Matrix might aid decision makers to evaluate treatment benefit and its certainty when comparing therapies across indications."

Journal • CNS Tumor • Neuroblastoma • Neuroendocrine Tumor • Oncology • Pediatrics • Rare Diseases • Solid Tumor

Growth patterns in patients with mucopolysaccharidosis VII. (PubMed, Mol Genet Metab Rep) - P2, P3 | "Patients with MPS VII and a history of NIHF had greater declines in height Z-score with age than did patients without a history of NIHF.Clinical trial registration: This retrospective analysis included patients enrolled in an open-label phase 2 study (UX003-CL203; ClinicalTrials.gov, NCT02418455), a randomized, placebo-controlled, blind-start phase 3 study (UX003-CL301; ClinicalTrials.gov, NCT02230566), or its open-label, long-term extension (UX003-CL202; ClinicalTrials.gov, NCT02432144)...Data will be shared via secured portal. The study protocol and statistical analysis plan for this study are available on the relevant clinical trial registry websites with the tabulated results."

Journal • Hunter Syndrome

Dose-dependent effects of enzyme replacement therapy on skeletal disease progression in mucopolysaccharidosis VII dogs. (PubMed, Mol Ther Methods Clin Dev) - "Enzyme replacement therapy (ERT) for MPS VII using recombinant human β-glucuronidase (vestronidase alfa) was recently approved for use in patients; however, to date there have been no studies evaluating therapeutic efficacy in a large animal model of MPS VII...Vertebral bone disease was recalcitrant to ERT irrespective of dose. Overall, our findings indicate that ERT administered at higher doses results in significantly improved skeletal disease outcomes in MPS VII dogs."

Journal • Hunter Syndrome • Lysosomal Storage Diseases • Metabolic Disorders • Orthopedics • Rare Diseases • Rheumatology

IUERT: In Utero Enzyme Replacement Therapy for Lysosomal Storage Diseases (clinicaltrials.gov) - P1 | N=10 | Recruiting | Sponsor: University of California, San Francisco | Trial completion date: Apr 2032 ➔ Jul 2032 | Trial primary completion date: Apr 2031 ➔ Jul 2031

Trial completion date • Trial primary completion date • Gaucher Disease • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Pompe Disease • Rare Diseases