Xenpozyme (olipudase alfa) / Sanofi - LARVOL DELTA

Interstitial lung disease in acid sphingomyelinase deficiency type B before and after olipudase alfa enzyme replacement therapy (ERS 2026) - "9-12 months after ERT initiation, most patients improved DLCO, TLC and 6MWT distance. Follow-up imaging showed a reduction in HRCT score. These results are in line with clinical trials data suggesting a potential benefit of ERT in ASMD type B."

Cardiovascular • Genetic Disorders • Interstitial Lung Disease • Lysosomal Storage Diseases • Musculoskeletal Pain • Pulmonary Disease • Rare Diseases • Respiratory Diseases

Fat Mass deficiency evidence in an ASMD patient: implications for nutritional management and follow-up (SSIEM 2026) - "ERT with olipudase alfa was introduced at 20 months for compassionate use...This case highlights the importance of body composition assessment and targeted nutritional counseling integrated into multidisciplinary management of children with ASMD on ERT. Long-term real-life follow-up is necessary in ASMD patients to clarify whether BMI alterations are related to the disease itself, treatment response, or inadequate nutrient intake."

Clinical • Gaucher Disease • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders

Impact on biochemical markers following reduced dose olipudase alfa in adults with acid sphingomyelinase deficiency (SSIEM 2026) - "In the short term, a significant reduction in olipudase alfa dose was not associated with any deterioration in biochemical markers, or clinical symptoms, in adults with ASMD. In patients, who are stable, with good disease clearance already achieved by treatment, this opens the possibility of maintaining disease control with lower treatment doses. Further studies should be done to investigate this."

Clinical • Genetic Disorders • Lysosomal Storage Diseases

The way they walk - neurological involvement in acid sphingomyelinase deficiency (SSIEM 2026) - "Enzyme replacement therapy (olipudase alfa) does not cross the blood–brain barrier and does not address neurological manifestations, thus the importance of long-term neurological surveillance in patients with ASMD, including those initially classified as non-neuronopathic. Early recognition of neurological signs is essential for optimal management and follow-up."

Alzheimer's Disease • Ataxia • Cognitive Disorders • Developmental Disorders • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Movement Disorders • Rare Diseases

From Childhood to Adulthood: Descriptive Analysis of Clinical Features in Patients with Acid Sphingomyelinase Deficiency (SSIEM 2026) - "This study highlights the clinical heterogeneity of ASMD across age groups. ASMD should be considered in the differential diagnosis of interstitial lung disease and hepatosplenomegaly. Biomarkers such as LysoSM levels are useful for subtype differentiation and may facilitate diagnosis."

Clinical • Cardiomyopathy • Cardiovascular • Dyslipidemia • Fibrosis • Genetic Disorders • Hematological Disorders • Hepatology • Hypertrophic Cardiomyopathy • Immunology • Interstitial Lung Disease • Liver Cirrhosis • Lysosomal Storage Diseases • Metabolic Disorders • Pulmonary Disease • Respiratory Diseases • Thrombocytopenia

Three-year experience with olipudase alfa therapy in acid sphingomyelinase deficiency in pediatric patients in Croatia (SSIEM 2026) - "To our knowledge, this is one of the longest reported follow-ups of olipudase alfa treatment in children. After three years, sustained positive effect was observed in reduction of organomegaly, improvement or stabilization of pulmonary function, lipid profile and bone mineral density and promotion of growth. Therapy was generally well tolerated, with few minor adverse events including rash, bronchospasm, aminotransferases increase and pyrexia."

Clinical • CNS Disorders • Epilepsy • Genetic Disorders • Hematological Disorders • Lysosomal Storage Diseases • Pediatrics • Thrombocytopenia

Olipudase Alfa for Acid Sphingomyelinase Deficiency: evidence of efficacy from the Italian Compassionate Use Program (SSIEM 2026) - "Longer-term studies are needed to better define predictors of response and optimize patient management. Acknowledgements: SIMMESN Italian Enzyme Replacement Therapy Study Group."

Clinical • Genetic Disorders • Hematological Disorders • Immunology • Lysosomal Storage Diseases

A challenging case of ASMD (acid sphingomyelinase deficiency): A severe interstitial lung disorder in an asplenic patient. (PubMed, Mol Genet Metab Rep) - "Treatment with olipudase alfa resulted in significant clinical, functional, and biomarker improvement despite advanced age and disease severity. This case supports the benefit of enzyme replacement therapy in patients with complex, late-presenting ASMD."

Journal • Frontotemporal Lobar Degeneration • Genetic Disorders • Interstitial Lung Disease • Lysosomal Storage Diseases • Metabolic Disorders • Pulmonary Disease • Rare Diseases • Respiratory Diseases

Access to orphan drugs in adults with inherited metabolic diseases in Switzerland: a single-center retrospective cohort study. (PubMed, Orphanet J Rare Dis) - P | "In this cohort from a specialized adult metabolic clinic, most patients with an indication for OD therapy accessed treatment. However, administrative burden, fragmented reimbursement procedures, and regulatory delays may still affect timely treatment initiation in certain situations. These findings highlight the need for continued efforts to streamline regulatory and reimbursement pathways and to ensure equitable access to innovative therapies for rare diseases."

Journal • Orphan drug • Retrospective data • Metabolic Disorders • Rare Diseases

Olipudase alfa IgE-mediated anaphylaxis prevented by omalizumab and tailored desensitization in a child with acid sphingomyelinase deficiency. (PubMed, Pediatr Allergy Immunol) - No abstract available

Journal • Genetic Disorders • Lysosomal Storage Diseases

Improvement in quality of life and general functions in pediatric acid sphingomyelinase deficiency patients after receiving olipudase alfa: A single-center experience in Taiwan. (PubMed, Mol Genet Metab Rep) - "ERT improves functional capacity and quality of life in two pediatric patients with chronic neurovisceral ASMD A/B. Further data from larger samples are required to confirm these findings."

HEOR • Journal • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Pediatrics • Rare Diseases

Adults With Acid Sphingomyelinase Deficiency Have Sustained Improvements in Clinical Outcomes With up to 5 Years of Olipudase Alfa Enzyme Replacement Therapy: ASCEND Trial Final Results. (PubMed, J Inherit Metab Dis) - "No new safety issues emerged during the trial extension and 98% of treatment emergent adverse events were mild/moderate. Improvements in visceral ASMD disease with olipudase alfa treatment will significantly impact the disease burden for those with this progressive multiorgan disorder."

Clinical • Clinical data • Journal • Genetic Disorders • Hepatology • Interstitial Lung Disease • Lysosomal Storage Diseases • Metabolic Disorders • Pulmonary Disease • Rare Diseases • Respiratory Diseases

Acid Sphingomyelinase Activity in Dried Blood Spot from Neonatal Intensive Care Unit-Admitted Neonates: A Pilot Study for Expanded Newborn Screening in Japan. (PubMed, Int J Neonatal Screen) - "Acid sphingomyelinase deficiency (ASMD) is currently treatable with olipudase alfa, increasing the need for early newborn screening (NBS)...In neonates with a birth weight < 2000 g, ASM increased significantly on repeat sampling (mean difference, 1.60 μmol/h/L; p < 0.0001; Cohen's d = 0.912). These findings support NICU-specific reference ranges, hematology-informed interpretations, repeat testing after maturation, and the use of second-tier biomarkers for ASMD NBS implementation in Japan."

Journal • Critical care • Frontotemporal Lobar Degeneration • Genetic Disorders • Hematological Disorders • Lysosomal Storage Diseases • Metabolic Disorders

Olipudase alfa treatment for pediatric acid sphingomyelinase deficiency in Egypt: A prospective, observational cohort study with an interventional subgroup. (PubMed, Mol Genet Metab Rep) - "This case series contributes to the clinical and biochemical understanding of ASMD and may help reduce diagnostic delays and improve clinical management. Olipudase alfa was generally well tolerated, and promising clinical improvements were observed."

Journal • Observational data • Frontotemporal Lobar Degeneration • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Pediatrics

Pathogenic Variants and Olipudase Alfa Treatment of Patients With Acid Sphingomyelinase Deficiency in Taiwan. (PubMed, Mol Genet Genomic Med) - "This study highlights distinct genotype-phenotype correlations in ASMD and supports the clinical benefits of olipudase alfa. Increased awareness and early diagnosis, potentially through newborn screening, are essential for optimizing outcomes in ASMD."

Journal • Frontotemporal Lobar Degeneration • Genetic Disorders • Hematological Disorders • Interstitial Lung Disease • Lysosomal Storage Diseases • Metabolic Disorders • Pulmonary Disease • Respiratory Diseases • Thrombocytopenia

A real-world evidence study into the usage of olipudase alfa for acid sphingomyelinase deficiency in the United States (ACMG 2026) - "This study reveals delays in diagnosis, variable institutional treatment criteria, and payer barriers as key challenges to olipudase alfa use. These findings underscore the need for standardized guidelines, broader diagnostic education, comprehensive monitoring, and improved insurance access."

Clinical • HEOR • Real-world • Real-world evidence • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Natural-History Mapping of Lysosomal Storage Disorders (LSDs): Gaucher Disease as a Model for Precision Care. (PubMed, J Inherit Metab Dis) - P | "Key observations include: (i) Whole-gene sequencing has expanded genotype-phenotype maps, revealing more than 70 recombinant GBA alleles that confound panel tests; (ii) registry trajectories suggest that formal multi-state models could capture treatment-modified courses and silent endpoints-monoclonal gammopathy, malignancy, Parkinson's disease, pulmonary arterial hypertension-better than current summary statistics; (iii) lyso-Gb1 outperforms legacy biomarkers and now serves as a second-tier newborn-screening marker; (iv) Robust natural-history evidence has already underpinned regulatory approvals across several lysosomal disorders-including olipudase alfa for ASMD, cerliponase alfa for CLN2, vestronidase alfa for MPS VII, and sebelipase alfa for infantile-onset LAL-D-demonstrating that well-curated registries can serve as viable external controls for future LSD submissions. Gaucher disease offers a working template that, when extended across the LSD spectrum,..."

Biomarker • Journal • Review • Cardiovascular • CNS Disorders • Gaucher Disease • Genetic Disorders • Hypertension • Lysosomal Storage Diseases • Metabolic Disorders • Monoclonal Gammopathy • Movement Disorders • Oncology • Parkinson's Disease • Pulmonary Arterial Hypertension • Pulmonary Disease • Rare Diseases • Respiratory Diseases

Innovation in Off-Patent Competitive Environment: Key Learnings From Successes and Failures (ISPOR-EU 2025) - "Products were evaluated based on payer-perceived value, with higher ratings classified as ASMR III or "considerable added benefit" (or better), and lower ratings as ASMR V/VI or "no added benefit." Only a few products (e.g., Camzyos and Xenpozyme) achieved positive P&MA outcomes in off-patent spaces, largely due to high unmet need and meaningful improvements in clinical or quality-of-life outcomes. Success in off-patent environments remains rare and hinges on clear differentiation, high unmet need, and robust clinical evidence. Payers expect incremental benefit demonstrated through well-designed trials, with quality-of-life and secondary endpoints viewed as supportive but not sufficient. Trial design limitations remain a major barrier to positive HTA and pricing outcomes."

Plasma Lyso-Sphingomyelin Levels Correlate with Baseline Disease and Decline with Olipudase Alfa Treatment in Clinical Trials of Adults and Children with Acid Sphingomyelinase Deficiency (SSIEM 2023) - No abstract available

Clinical • Genetic Disorders • Lysosomal Storage Diseases

Plasma Lyso-Sphingomyelin Levels Correlate with Baseline Disease and Decline with Olipudase Alfa Treatment in Clinical Trials of Adults and Children with Acid Sphingomyelinase Deficiency (SSIEM 2023) - No abstract available

Clinical • Genetic Disorders • Lysosomal Storage Diseases

Plasma Lyso-Sphingomyelin Levels Correlate with Baseline Disease and Decline with Olipudase Alfa Treatment in Clinical Trials of Adults and Children with Acid Sphingomyelinase Deficiency (SSIEM 2023) - No abstract available

Clinical • Genetic Disorders • Lysosomal Storage Diseases

Plasma Lyso-Sphingomyelin Levels Correlate with Baseline Disease and Decline with Olipudase Alfa Treatment in Clinical Trials of Adults and Children with Acid Sphingomyelinase Deficiency (SSIEM 2023) - P1, P1/2, P2/3 | "In summary, plasma lyso-sphingomyelin was highly elevated in untreated patients with ASMD and these elevations correlated with most indices of disease severity. Treatment with olipudase alfa led to rapid plasma lyso-sphingomyelin reduction."

Clinical • Genetic Disorders • Lysosomal Storage Diseases

Continued improvement in liver and lipid outcomes in clinical trials of olipudase alfa in children and adults with chronic acid sphingomyelinase deficiency treated for 2 to 6.5 years (SSIEM 2023) - P1, P1/2, P2, P2/3 | "Olipudase alfa was generally safe and well tolerated; most adverse events (AEs) were mild or moderate with no trial withdrawals due to drug-related AEs. In summary, olipudase alfa treatment resulted in sustained improvements or normalization in liver and lipid parameters in adults and children with ASMD."

Clinical • Dyslipidemia • Genetic Disorders • Hepatology • Hypertriglyceridemia • Liver Failure • Lysosomal Storage Diseases • Pulmonary Disease • Rare Diseases • Respiratory Diseases

Current and Emerging Treatments for Acid Sphingomyelinase Deficiency. (PubMed, Drugs) - "In 2022, a specific enzyme replacement therapy with olipudase alfa was approved, and the results available indicate that it changed the therapeutic landscape for patients with acid sphingomyelinase deficiency type B and A/B. Research is being developed to address the needs of patients with acid sphingomyelinase deficiency type A, with gene therapy remaining as a promising approach."

Journal • Review • Gene Therapies • Genetic Disorders • Hematological Disorders • Lysosomal Storage Diseases • Rare Diseases • Thrombocytopenia • Transplantation

Lysosomal storage disorders. (PubMed, Semin Respir Crit Care Med) - "Olipudase alfa administration decreased liver and spleen volume, increased DLCO value and improved radiological lung involvement. Available enzyme replacement therapy supports an early diagnosis to implement therapy before any irreversible organ damage."

Journal • Genetic Disorders • Infectious Disease • Interstitial Lung Disease • Lysosomal Storage Diseases • Metabolic Disorders • Pediatrics • Pulmonary Disease • Rare Diseases • Respiratory Diseases • Thrombocytopenia