Xenpozyme (olipudase alfa) / Sanofi - LARVOL DELTA

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

Real-life impacts of olipudase alfa: experiences of adults receiving enzyme replacement therapy for acid sphingomyelinase deficiency-results from an international survey study. (PubMed, Orphanet J Rare Dis) - "This study highlights the burden of ASMD and the positive impact of olipudase alfa on patients' quality of life. Findings reinforce the importance of early diagnosis and accessible treatment. Despite the favourable outcomes, there remains a need for therapies targeting neurological manifestations and reducing treatment burden. Future research should focus on long-term outcomes and continue to prioritise patient-reported experiences to guide therapeutic development."

Journal • Retrospective data • Frontotemporal Lobar Degeneration • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Efficacy and Safety of Olipudase Alfa for the Treatment of Acid Sphingomyelinase Deficiency (ASMD): A Systematic Review and Meta-Analysis. (PubMed, Am J Med Genet A) - "The olipudase alfa demonstrates substantial clinical benefits in ASMD, significantly improving lung function and reducing organomegaly. Further studies are needed to confirm long-term safety and efficacy."

Journal • Retrospective data • Review • Frontotemporal Lobar Degeneration • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Long-Term Safety and Clinical Outcomes With Olipudase Alfa Enzyme Replacement Therapy in Children and Adolescents With Acid Sphingomyelinase Deficiency. (PubMed, J Inherit Metab Dis) - P2 | " Enzyme replacement therapy with olipudase alfa in children and adolescents with chronic ASMD was well-tolerated with clinically meaningful improvements in multiple disease parameters. Trial Registration: NCT02004704."

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

Outcome of enzyme replacement therapy for hematological and visceral manifestations in children with acid sphingomyelinase deficiency: a single center experience in upper Egypt. (PubMed, Mol Cell Pediatr) - "Our findings indicate that olipudase alfa provides significant benefits in key hematological and visceral clinical outcomes in pediatric patients with ASMD."

Journal • Dermatology • Genetic Disorders • Hematological Disorders • Immunology • Interstitial Lung Disease • Lysosomal Storage Diseases • Pediatrics • Pulmonary Disease • Respiratory Diseases • Thrombocytopenia • Urticaria

Acid sphingomyelinase deficiency: A review (PubMed, Rev Med Interne) - "Knowing and recognizing this disease is important, especially since there is an effective specific treatment through enzyme replacement therapy. In this article, we describe the clinical manifestations of acid sphingomyelinase deficiency, to understand when to suspect it, how to confirm it, and how to manage it."

Journal • Review • Frontotemporal Lobar Degeneration • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Reversal of Interstitial Lung Disease in Children and Adults With Chronic Acid Sphingomyelinase Deficiency Treated With Olipudase Alfa Enzyme Replacement Therapy (ATS 2025) - P1, P1/2, P2, P2/3 | "Olipudase-alfa treatment results in progressive resolution of GGO and normalization of lung parenchyma by imaging and mechanics (FVC) with marked improvement in gas exchange (DLCO) in adults and children with ASMD."

Clinical • Dyslipidemia • Genetic Disorders • Interstitial Lung Disease • Lysosomal Storage Diseases • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

Development of a Durable Gene Therapy for Targeting CNS and Visceral Pathologies in Acid Sphingomyelinase Deficiency (ASGCT 2025) - "The current enzyme replacement therapy (ERT), Olipudase alfa, is limited to treating non-CNS pathologies due to its inability to cross the blood-brain barrier (BBB)...This innovative gene therapy approach not only reduces the need for frequent ERT infusions required by the current standard-of-care but also effectively targets and mitigates CNS deficits in ASMD, making it a potential therapeutic to address unmet need in neurovisceral ASMD. Disease Focus of Abstract:Storage/Lysosomal Disorders"

Gene therapy • CNS Disorders • Gene Therapies • Genetic Disorders • Lysosomal Storage Diseases • Rare Diseases • TFRC

A case of acid sphingomyelinase deficiency type B with prominent histiocytes with engulfed nucleated cells and compound heterozygosity. (PubMed, J Hematop) - "The patient was started on enzyme replacement therapy with olipudase alfa...One recent study reported finding emperipolesis in some cases of ASMD. Thus, this may be an uncommon but recurrent finding in some NPB patients."

Journal • Frontotemporal Lobar Degeneration • Gastrointestinal Disorder • Genetic Disorders • Hematological Disorders • Hepatology • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

A Study to Evaluate Safety and Tolerability of Olipudase Alfa in Pediatric and Adult Participants With Acid Sphingomyelinase Deficiency (ASMD) Who Completed the DFI12712 or the LTS13632 Study in France (clinicaltrials.gov) - P2 | N=3 | Completed | Sponsor: Sanofi

New P2 trial • Frontotemporal Lobar Degeneration • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Pediatrics

Benefits of early intervention with olipudase alfa in symptomatic children with acid sphingomyelinase deficiency: A sibling case-comparison study. (PubMed, Mol Genet Metab Rep) - "Treatment has resulted in sustained improvements in both patients. These findings suggest that early intervention with ERT in ASMD may have cumulative benefits for pediatric health and motivate early screening for ASMD in pediatric patients."

Journal • CNS Disorders • Genetic Disorders • Hematological Disorders • Interstitial Lung Disease • Lysosomal Storage Diseases • Metabolic Disorders • Pediatrics • Pulmonary Disease • Rare Diseases • Respiratory Diseases

From Genes to Treatment: Literature Review and Perspectives on Acid Sphingomyelinase Deficiency in Children. (PubMed, Diagnostics (Basel)) - "Since 2022, the FDA has given a green light to a revolutionary enzymatic replacement therapy with human recombinant ASM called Olipudase-alfa. Clinical trial outcomes support its reliability and efficacy in the pediatric population."

Journal • Review • Frontotemporal Lobar Degeneration • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Pediatrics • Pulmonary Disease • Respiratory Diseases

Novel Case of Olipudase Alfa Enzyme Replacement Therapy to Treat Niemann-Pick Disease Type-B Following Lung Transplant (ISHLT 2025) - "At week 30, bilirubin, liver transaminases and thrombocytopenia have improved. No recurrence of native lung disease or acute rejection has hitherto been observed in his allograft on routine surveillance with transbronchial biopsies.Summary This novel case study suggests that treatment of NPD-B with Olipudase Alfa following lung transplant is well-tolerated, safe, feasible and improves visceral manifestations of the condition."

Clinical • Atherosclerosis • Cardiovascular • Dyslipidemia • Frontotemporal Lobar Degeneration • Genetic Disorders • Hematological Disorders • Interstitial Lung Disease • Lysosomal Storage Diseases • Metabolic Disorders • Pulmonary Disease • Respiratory Diseases • Thrombocytopenia • Transplant Rejection • Transplantation • APOA1 • APOB

OPERA: Data Analysis of Adult and Pediatric Participants With Acid Sphingomyelinase Deficiency (ASMD) on Early Access to Olipudase Alfa in France (clinicaltrials.gov) - P=N/A | N=40 | Completed | Sponsor: Sanofi | Recruiting ➔ Completed

Trial completion • Genetic Disorders • Lysosomal Storage Diseases • Pediatrics

Case Report: Two years of compassionate use with Olipudase-alfa in a child with neurovisceral acid sphingomyelinase deficiency. (PubMed, Front Pediatr) - "This report highlights the importance of early intervention, even in patients with neurovisceral phenotypes, as it can enhance quality of life for both patients and their families. Our findings advocate for reconsidering treatment eligibility criteria based solely on clinical phenotype definitions, highlighting the need for a tailored approach in ASMD management."

Journal • Frontotemporal Lobar Degeneration • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

The impact of sphingomyelin on the pathophysiology and treatment response to olipudase alfa in acid sphingomyelinase deficiency. (PubMed, Genet Med Open) - "This review article expounds on the complex and multifaceted role of sphingomyelin in the pathophysiology of ASMD and discusses the animal studies and human interventional trials demonstrating that sphingomyelin and its related metabolites are linked to ASMD clinical manifestations, disease burden, and response to treatment. The relationship between the diverse manifestations of ASMD and sphingomyelin accumulation and the connections between sphingomyelin clearance and reversal of the noncentral nervous system manifestations by olipudase alfa therapy also are described."

Journal • Review • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases