Kanuma (sebelipase alfa) / AstraZeneca - LARVOL DELTA

Pharmaceutical protein production by transgenic chickens: several viewpoints towards the next stage. (PubMed, Protein Expr Purif) - "Several pharmaceuticals produced by transgenic chickens, Kanuma and Epovet, are already in commercial use, which indicates the potential cost competitiveness of this approach as an "animal bioreactor." Since the establishment of reliable cultivation and genetic modification methods for chicken primordial germ cells, the robustness of this system has increased significantly...Recent advances in site-specific genome modification technology are promising in this regard, provided that patent disputes can be resolved. The integration of these emerging strategies into transgenic chicken bioreactor platforms could further enhance their competitiveness as systems for recombinant protein production."

Journal

Best Practices for the Nutritional Management of Infantile-Onset Lysosomal Acid Lipase Deficiency: A Case-Based Discussion. (PubMed, Nutrients) - "Treatment takes the two-pronged approach of sebelipase alfa, a human lysosomal acid lipase enzyme replacement therapy (ERT) that improves lipid metabolism, combined with nutritional management...A review of guidance for best practice nutritional management is needed. This narrative review aims to provide updated recommendations and guidance for the optimal nutritional management of infantile-onset LAL-D."

Journal • Review • Gastrointestinal Disorder • Inflammation • Metabolic Disorders

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

Hepatic Steatosis: A Presentation of Cholesteryl Ester Storage Disease. (PubMed, ACG Case Rep J) - "We describe a case of late-onset cholesteryl ester storage disease in a woman with elevated liver enzymes, histologic evidence of microvesicular steatosis and cirrhosis, with a confirmed LIPA mutation, who initiated enzyme replacement therapy with sebelipase alfa. This case highlights the importance of considering hereditary disorders of lipid metabolism in patients presenting unexpectedly with steatotic liver disease in the absence of significant metabolic risk factors."

Journal • Dyslipidemia • Fibrosis • Genetic Disorders • Hepatology • Immunology • Metabolic Disorders

Long-term clinical outcomes in lysosomal acid lipase deficiency: Fibrosis regression with sebelipase alfa therapy. (PubMed, Can Liver J) - "While early initiation of ERT may optimize outcomes, this case supports its continued use in advanced disease stages. Further research is needed to assess the long-term metabolic and histologic benefits of ERT in LAL-D patients."

Clinical data • Journal • Dyslipidemia • Fibrosis • Hematological Disorders • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders

Survival, growth, and safety findings in patients with rapidly progressive, infantile-onset LAL-D: Results from the international LAL-D registry. (PubMed, Mol Genet Metab) - P | "Four patients among 7 tested developed antidrug antibodies, and 3 had positive results for neutralizing antidrug antibodies. These results confirmed the dramatic survival and metabolic benefit associated with sebelipase alfa ERT in patients with symptomatic, rapidly progressive LAL-D."

Journal • Hematological Disorders • Hemophagocytic lymphohistiocytosis • Hepatology • Immunology • Inflammation • Liver Failure • Metabolic Disorders • Rare Diseases

Disease Progression Modeling for an Ultra-Rare Disease: Lysosomal Acid Lipase Deficiency (LAL-D) (ISPOR-EU 2025) - "Both profiles were assessed separately, and for each, three treatment scenarios were evaluated: untreated patients, early treatment with sebelipase alfa (SA), and delayed SA treatment post-diagnosis... To the best of our knowledge, this is the first model to simulate LAL-D progression. The model supports early treatment of LAL-D patients to improve survival and manage cardiovascular events."

Cardiovascular • Dyslipidemia • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Myocardial Infarction • Rare Diseases

Enzyme replacement therapy in cholesteryl ester storage disease: A case report on lysosomal acid lipase deficiency management. (PubMed, J Clin Lipidol) - "This case underscores the importance of early recognition of CESD in patients with unexplained dyslipidemia, elevated liver enzymes, and growth delay. Timely initiation of sebelipase alfa resulted in favorable biochemical and clinical outcomes. Comprehensive diagnostic evaluation-including enzymatic and genetic testing-is critical for accurate diagnosis and personalized management of LAL-D."

Journal • Dyslipidemia • Metabolic Disorders

Effects of Two Dental Implant Micromotor Systems for Dental Implant Placement on Implant Stability and Removal Torque: An Animal Experiment. (PubMed, Materials (Basel)) - "In a within-animal crossover design, twenty titanium implants (AnyOne fixture; internal type; diameter, 3.5 mm; length, 7.0 mm; Megagen, Daegu, Republic of Korea) were placed in the tibiae of five rabbits using a conventional micromotor system (NSK group: SurgicPro+; NSK, Kanuma, Japan) and a diode laser-integrated micromotor system (SAESHIN group: BLP 10; Saeshin, Daegu, Republic of Korea)...The immediate ISQ should be interpreted as stiffness under fixed torque rather than superior device-dependent interlocking. These findings support the clinical interchangeability of the two systems for early osseointegration endpoints in preclinical settings."

Journal

Sebelipase Alfa Improves Aminotransferase Levels in Lysosomal Acid Lipase Deficiency: Data From an International Registry. (PubMed, Liver Int) - P | "Aminotransferase levels were elevated in most patients with LAL-D at baseline. There were sustained improvements with sebelipase alfa treatment."

Journal • Observational data

† Sebelipase alfa results in sustained improvement of lipid parameters in symptomatic LAL-D: Longitudinal data from the International LAL-D Registry (NLA 2025) - P | "Conclusions Patients with LAL-D exhibit marked lipid abnormalities at baseline, which are most severe in patients aged < 12 years and are in the range of heterozygous familial hypercholesterolemia. Significant improvements in LDL-C and HDL-C in all age groups were observed within 1 year of treatment with sebelipase alfa, with results sustained over 3 years."

Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Metabolic Disorders • Rare Diseases

LYSOSOMAL ACID LIPASE DEFICIENCY: A DECADE OF SLOVENIAN EXPERIENCE IN SCREENING, DIAGNOSIS AND INSIGHTS INTO COHORT CHARACTERISTICS (ESPGHAN 2025) - "Sebelipase alpha treatment, initiated in three patients, improved cholesterol, transaminase levels, and liver steatosis...Slovenia's successful FH screening program helped diagnose three presymptomatic patients with LAL-D. Two additional patients were diagnosed outside the screening program, but by promptly using its NGS dyslipidemia gene panel, we significantly reduced diagnostic delays, enabling earlier treatment and improved outcomes."

Dyslipidemia • Familial Hypercholesterolemia • Gastroenterology • Genetic Disorders • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Pediatrics

SEBELIPASE ALFA IMPROVES LIVER AND LIPID PARAMETERS IN PATIENTS WITH LYSOSOMAL ACID LIPASE DEFICIENCY: RESULTS FROM THE INTERNATIONAL LAL-D REGISTRY (ESPGHAN 2025) - No abstract available

Clinical

Sebepliase alfa improves lipid metabolism and liver outcomes in pediatric patients with lysosomal acid lipase deficiency (EASL 2025) - P | "The aim of this analysis was to quantify baseline lipid and liver parameters in patients with LAL-D and examine if these values changed in patients treated with the LAL enzyme replacement therapy sebelipase alfa (SA)... Patients with LAL-D diagnosed before age 18 years had substantial signs of liver injury and dysregulation of lipid metabolism, with ~75% of patients meeting the LDL-C criterion of familial hypercholesterolemia. Treatment with SA may improve lipid metabolism (LDL-C, HDL-C) and parameters of liver injury (ALT, AST) in this population."

Clinical • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Hepatology • Liver Failure • Metabolic Disorders • Pediatrics

Successful pregnancy outcome in a woman with cholesteryl ester storage disease treated with enzyme replacement therapy. (PubMed, J Clin Lipidol) - "Enzyme replacement therapy (ERT) using sebelipase alfa, a recombinant form of LAL, is effective in improving lipid profiles and reversing liver dysfunction in patients with CESD...Given the absence of CESD complications, colestimide was the only medication administered during pregnancy...Following delivery, transient triglycerides, low-density lipoprotein-cholesterol, and liver enzyme increases were observed. However, restarting ERT led to a gradual improvement in the liver function and lipid profile."

Journal • Atherosclerosis • Dyslipidemia • Hepatology • Liver Failure • Metabolic Disorders • Obstetrics

EXTENSIVE THROMBOSIS AFTER UTILIZING ECMO IN A CHILD WITH LYSOSOMAL ACID LIPASE DEFICIENCY (SCCM 2025) - "Description: A 20-month-old female with WD receiving weekly ERT (Sebelipase) via an indwelling central line since 5 weeks of age presented with fever and central line erythema, then rapidly progressed to severe vasoplegic shock. She required intubation and her vascular tone was refractory to norepinephrine, epinephrine, and vasopressin infusions, as well as stress dose hydrocortisone and methylene blue...While there are no reports of ECMO outcomes for patients with WD, the ELSO database identified 4 children under age 10 years with some form of LAL-D who received ECMO, and only 2 survived to discharge. Due to known thrombotic complications, we would consider these patients high-risk for ECMO support, and suggest a thoughtful anticoagulation strategy to combat the observed thrombotic complications."

Clinical • Cardiovascular • Dermatology • Hematological Disorders • Ischemic stroke • Metabolic Disorders • Thrombosis

The role of lysosomal acid lipase deficiency in dyslipidemia and liver disorders. (PubMed, Rev Esp Enferm Dig) - "CESD often mimics other metabolic and hepatic conditions, such as familial hypercholesterolemia or non-alcoholic fatty liver disease, necessitating high clinical suspicion and genetic confirmation for diagnosis. This case underscores the importance of recognizing CESD in patients with atypical dyslipidemia and persistent hepatic abnormalities, as early identification enables targeted therapeutic interventions, including Sebelipase alfa enzyme replacement therapy."

Journal • Cholestasis • Dyslipidemia • Familial Hypercholesterolemia • Fibrosis • Genetic Disorders • Hepatology • Immunology • Inflammation • Liver Failure • Lysosomal Storage Diseases • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Rare Diseases

Lysosomal Acid Lipase Deficiency: A Report of Two Cases and a Review of the Literature. (PubMed, Cureus) - "Since 2015, sebelipase alfa has been authorised for the treatment of LAL-D in the European Union, changing the course of this disease...Thus, most asymptomatic or minimally symptomatic patients might remain undiagnosed, and multiple complications without clear aetiology might arise, making this disease even harder to diagnose and manage. Nevertheless, even though the introduction of enzyme replacement therapy has improved outcomes for many patients, there still remains a need for increased awareness and understanding of this rare condition among health professionals."

Journal • Review • Dyslipidemia • Genetic Disorders • Hepatology • Immunology • Infectious Disease • Inflammation • Metabolic Disorders • Pediatrics

Health Technology Appraisals of Gene Therapies Appraised Through NICE Highly Specialized Technology Route (ISPOR-EU 2024) - " To date (May 2024), NICE has appraised eight gene therapies through the HST route; five single-dose therapies (Strimvelis; Luxturna; Zolgensma; Libmeldy; Upstaza), and three enzyme replacement therapies with long-term dosages (Strensiq; Lamzede; Kanuma)... This overview of prior NICE HST appraisals of gene therapies provides insight to the potential issues faced by all stakeholders involved in technology appraisals of these innovative treatments. It also demonstrates the array of products that “gene therapies” captures, the differences in acquisition prices, and variation in economic model structure and approach."

Gene therapy • Gene Therapies • Rare Diseases

PATIENT CHARACTERISTICS, MANAGEMENT, AND PROGRESSION OF LYSOSOMAL ACID LIPASE DEFICIENCY (LAL-D) IN FRANCE USING REAL-WORLD DATA FROM THE NATIONAL HEALTH DATA SYSTEM (SNDS) (AASLD 2024) - "In this first study using SNDS data to investigate patients with LAL-D, the analysis showed that most patients presented severe symptoms and comorbidities. The mortality rate among untreated infants with sebelipase alfa was high. Furthermore, despite the severity of the disease, several patients remained untreated, highlighting potential gap in clinical management of LAL-D."

Clinical • Real-world • Real-world evidence • Cardiovascular • Diabetes • Dyslipidemia • Fibrosis • Hepatology • Immunology • Liver Failure • Lysosomal Storage Diseases • Metabolic Disorders • Portal Hypertension • Pulmonary Arterial Hypertension • Rare Diseases • Type 2 Diabetes Mellitus

SUSTAINED IMPROVEMENT OF AMINOTRANSFERASE LEVELS IN PATIENTS WITH LYSOSOMAL ACID LIPASE DEFICIENCY TREATED WITH SEBELIPASE ALFA ENZYME REPLACEMENT THERAPY: LONGITUDINAL DATA FROM THE INTERNATIONAL LYSOSOMAL ACID LIPASE DEFICIENCY REGISTRY (AASLD 2024) - P | "Liver injury in patients with LAL-D is common early in life, as demonstrated by baseline ALT and AST levels. Sustained reduction of aminotransferases was observed in patients receiving ERT. Further longitudinal studies are needed to evaluate disease progression and the effects of sebelipase alfa in patients with LAL-D."

Clinical • Hepatology • Liver Failure • Rare Diseases

LYSOSOMAL ACID LIPASE DEFICIENCY: SEVEN YEARS JOURNEY OF ENZYME REPLACEMENT TREATMENT UNDER THE AGE OF FOUR (SSIEM 2024) - "Here, we present this case as the infantile form of LAL deficiency except the newborn period is very rare, and to emphasize the favorable response to Sebelipase alfa in terms of clinical, laboratory, and histological findings. Also with this case, we want to point out the nonspecific clinical manifestations of LAL deficiency in infancy, mimicking various acquired and inherited disorders. Phenylketonuria"

Anemia • Dyslipidemia • Fibrosis • Genetic Disorders • Hematological Disorders • Hepatology • Immunology • Infectious Disease • Inflammation • Liver Failure • Metabolic Disorders • Phenylketonuria • Rare Diseases

Evaluation of 73 Enlisted Patients for Liver Transplant with Unknown Etiology Reveals a Late-Diagnosed Case of Lysosomal Acid Lipase Deficiency. (PubMed, Int J Mol Sci) - "Detecting low/absent LAL activity and identifying the LIPA causal variant are essential for diagnosis and specific treatment, as well as for appropriate genetic counseling. Early diagnosis, along with sebelipase alfa therapy, may improve the prognosis of affected patients."

Journal • Dyslipidemia • Hepatology • Liver Failure • Metabolic Disorders • Transplantation

Twice weekly dosing with Sebelipase alfa (Kanuma®) rescues severely ill infants with Wolman disease. (PubMed, Orphanet J Rare Dis) - "5 mg/kg twice weekly dosing with Sebelipase alfa rescues severely ill infants with WD by increasing substrate clearance. There is biologically relevant lipid accumulation in the 'trough' periods before the next dosing, even with this intensive regimen."

Journal • Metabolic Disorders

Sustained improvement of alanine aminotransferase levels in patients with lysosomal acid lipase deficiency treated with sebelipase alfa enzyme replacement therapy: longitudinal data from the international lysosomal acid lipase deficiency registry (EASL-ILC 2024) - P=N/A | "Findings from this first longitudinal analysis of International LAL-D Registry data reflect a favorable treatment response to ERT. ALT values were elevated in most patients at baseline. Following ERT treatment, most patients experienced improvements in ALT levels."

Clinical • Hepatology