Xenpozyme (olipudase alfa) / Sanofi - LARVOL DELTA

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

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

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

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

Application of Quantitative Systems Pharmacology Approaches to Support Pediatric Labeling in Rare Diseases. (PubMed, Handb Exp Pharmacol) - "The mechanistic nature of QSP models is well suited to pediatric extrapolation concepts, providing a quantitative method to assess disease and drug response similarity between adults and pediatric patients. The application of a QSP-based assessment of the disease and drug similarity in adult and pediatric patients in the clinical development program of olipudase alfa, a treatment for Acid Sphingomyelinase Deficiency (ASMD), illustrates the potential of this approach."

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

Imaging improvement in acid sphingomyelinase deficiency on enzyme replacement therapy. (PubMed, Mol Genet Metab) - No abstract available

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

Unexplained splenomegaly as a diagnostic marker for a rare but severe disease with an innovative and highly effective new treatment option: A case report. (PubMed, Mol Genet Metab Rep) - "Acid Sphingomyelinase Deficiency (ASMD) is a lysosomal storage disorder that can lead to severe complications if not promptly treated. This case aims to highlight the critical importance of early awareness of ASMD and to introduce, for the first time in the literature, a new and highly effective treatment option for children."

Journal • Gaucher Disease • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

LONG-TERM IMPACT OF OLIPUDASE ALFA TREATMENT IN CHILDREN WITH CHRONIC ACID SPHINGOMYELINASE DEFICIENCY: FINAL RESULTS OF THE ASCEND-PEDS TRIAL (SSIEM 2024) - P1/2, P2 | "Children with ASMD experienced significant improvements in hepatosplenomegaly and lung, lipid, and growth outcomes with ≥4Y of olipudase alfa treatment."

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

Efficacy and Safety data for olipudase alfa: the first and only disease specific treatment for ASMD type A/B or type B (non-CNS manifestations) (SSIEM 2024) - "Sponsored by Sanofi"

Clinical

ENZYME REPLACEMENT THERAPY FOR ACID SPHINGOMYELINASE DEFICIENCY - A REAL-WORLD EXPERIENCE OF A SINGLE CENTER IN BRAZIL (SSIEM 2024) - "The current disease-specific treatment is enzyme replacement therapy (ERT) with a recombinant human acid sphingomyelinase, olipudase alfa... ERT was safe, improved liver transaminases and hematological parameters, attenuated facial features, and markedly reduced hepatosplenomegaly."

Clinical • Real-world • Real-world evidence • Anemia • Cardiovascular • Dyslipidemia • Genetic Disorders • Hematological Disorders • Hepatology • Leukopenia • Lysosomal Storage Diseases • Portal Hypertension • Thrombocytopenia

EARLY RESULTS OF OLIPUDSE ALPHA TREATMENT IN A CASE DIAGNOSED WITH ACID SPHINGOMYELINASE DEFICIENCY (SSIEM 2024) - "Early initiation of ERT, a specific treatment for ASMD deficiency, in NP type B and A/B cases will cause changes in the natural course of the disease. Palavras-chave : ACID SPHINGOMYELINASE DEFICIENCY, OLIPUDASE ALPHA"

Clinical • Genetic Disorders • Infectious Disease • Interstitial Lung Disease • Lysosomal Storage Diseases • Pulmonary Disease • Respiratory Diseases

A REAL-WORLD EFFECT OF OLIPUDASE ALFA ON ASMD CHILDREN OF VARIABLE PRESENTATIONS (SSIEM 2024) - "Despite the short follow up period, olipudase alfa showed an exceptional effect on linear growth in type A/B patient as well as a noticeable decrease in organ volume, chest infiltration and normalization of hemoglobin and liver function tests. The effect on weight was variable between the three patients (keeping in mind that all patients had decrease in organ volumes which is part of their weight). Long term follow up is needed to verify the impact of olipudase alfa on other manifestations in type A/B patients."

Clinical • Real-world • Real-world effectiveness • Real-world evidence • Genetic Disorders • Hematological Disorders • Lysosomal Storage Diseases

ENZYME REPLACEMENT THERAPY FOR CHILDREN WITH ACID SPHINGOMYELINASE DEFICIENCY: A 3-YEAR REAL-WORLD EXPERIENCE AT A SINGLE CENTER IN TAIWAN (SSIEM 2024) - P=N/A | "The 3Y results in our study provide real-world experience indicating that olipudase alfa is safe and effective in improving clinical outcomes for pediatric chronic ASMD patients. Monitoring liver and spleen volumes, as well as liver stiffness, using abdominal ultrasonography and shear wave elastography, represents a noninvasive procedure that can monitor treatment efficacy during enzyme replacement therapy."

Clinical • Real-world • Real-world evidence • Genetic Disorders • Interstitial Lung Disease • Lysosomal Storage Diseases • Pediatrics • Pulmonary Disease • Respiratory Diseases

LONG-TERM IMPACT OF OLIPUDASE ALFA TREATMENT IN CHILDREN WITH CHRONIC ACID SPHINGOMYELINASE DEFICIENCY: FINAL RESULTS OF THE ASCEND-PEDS TRIAL (SSIEM 2024) - P1/2, P2 | "Children with ASMD experienced significant improvements in hepatosplenomegaly and lung, lipid, and growth outcomes with ≥4Y of olipudase alfa treatment."

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

CASE REPORT: TREATMENT WITH OLIPUDASE ALFA AMONG US ASMD PATIENTS WITH SIGNIFICANT NEUROLOGICAL SYMPTOMS (SSIEM 2024) - "By leveraging recruitment through WylderNation Foundation and PicnicHealth medical record data, this case study provides insight into the clinical outcomes of ERT in ASMD patients with more severe phenotypes."

Case report • Clinical • CNS Disorders • Developmental Disorders • Epilepsy • Gastrointestinal Disorder • Genetic Disorders • Lysosomal Storage Diseases

ACID SPHINGOMYELINASE DEFICIENCY - INITIAL OUTCOMES OF TREATMENT WITH ENZYME REPLACEMENT THERAPY IN INDIAN CHILDREN (SSIEM 2024) - "Olipudase alfa is the first diseasemodifying treatment approved for adults and children with ASMD. Replicating literature findings, the results from our data demonstrate the clinical efficacy and safety of ERT in patients with ASMD, specifically focusing on its impact on various clinical parameters and patient outcomes over a short term."

Clinical • Anemia • Dyslipidemia • Frontotemporal Lobar Degeneration • Genetic Disorders • Hematological Disorders • Lysosomal Storage Diseases

Transforming ASMD Management: Clinical Perspectives on Timely Diagnosis and Treatment of ASMD (SSIEM 2024) - "Cassiman and Ganesh will discuss the disease burden and unmet needs among patients with ASMD by leveraging real- world patient cases. This program will also feature olipudase alfa efficacy and safety data that supports use in appropriate real-world patients and highlight the significant impact of accurate diagnosis and timely intervention with olipudase alfa."

Clinical

Desensitization of olipudase alfa-induced anaphylaxis in a child with chronic neurovisceral acid sphingomyelinase deficiency. (PubMed, Mol Genet Metab Rep) - "We report a case of anaphylaxis to olipudase alfa in a child affected by chronic neurovisceral Acid sphingomyelinase deficiency (ASMD) and describe a 7-step desensitization procedure. This procedure, with the total administered dose of 0.03 mg/kg, followed by gradual dose escalation, allowed to reach the dose of 0.3 mg/kg without adverse reactions; however, at the second administration of the dose of 0.6 mg/kg our patient presented another adverse reaction suggesting the need of a different desensitization strategy."

Journal • Dermatology • Genetic Disorders • Immunology • Lysosomal Storage Diseases • Urticaria

On the role of excipients in biopharmaceuticals manufacture: Modelling-guided formulation identifies the protective effect of arginine hydrochloride excipient on spray-dried Olipudase alfa recombinant protein. (PubMed, Int J Pharm) - "The Arg-HCl effect was explained by the calculated thermal stability and structural order of the protein wherein Arg-HCl acted as a crowding agent to suppress protein aggregation and promote stabilization of Olipudase post-spray-drying. Therefore, by rational selection of appropriate excipients, our experimental and modelling dataset confirms spray-drying is a promising technology for the manufacture of Olipudase and demonstrates the potential to accelerate development of continuous manufacturing of parenteral biopharmaceuticals."

Journal