Kanuma (sebelipase alfa) / AstraZeneca - LARVOL DELTA

Wolman Disease with Homozygous LIPA p.Arg218Ter: One-Year Follow-Up After Early Sebelipase Alfa (SSIEM 2026) - "This case broadens the genotype– phenotype spectrum of LAL-D by documenting, to our knowledge, the first homozygous presentation of LIPA p.Arg218Ter associated with classic Wolman disease. It also highlights that Wolman disease may mimic secondary hemophagocytic lymphohistiocytosis and supports immediate LAL testing and expedited ERT when adrenal calcifications, hepatosplenomegaly, dyslipidemia, and hyperinflammation coexist. Early high-dose sebelipase alfa can transform an otherwise fatal course into survival beyond infancy, although growth and nutritional issues may persist."

Atopic Dermatitis • Dermatitis • Dyslipidemia • Hematological Disorders • Hemophagocytic lymphohistiocytosis • Hepatology • Hypertriglyceridemia • Immunology • Inflammation • Metabolic Disorders • Rare Diseases

Enzyme replacement therapy and stem cell transplantation in 9 patients with lysosomal acid lipase deficiency (SSIEM 2026) - "Even if this treatment carries a significant risk, SCT may be a viable treatment option for patients with rapidly progressive LAL-D, particularly those who have decreasing clinical response to sebelipase alfa. Clinicians should monitor weight-for-age development and other parameters throughout treatment in this vulnerable patient population."

Clinical • Hemophagocytic lymphohistiocytosis • Hepatology • Immunology • Rare Diseases • Transplantation

Infantile-onset lysosomal acid lipase deficiency – impact of fat intake on growth and duodenal histology. (SSIEM 2026) - "Treatment is with enzyme replacement therapy (Sebelipase alfa) and dietary substrate (lipid) reduction (DSR)...Commencing DSR at birth coincided with normal duodenal histology, with few foamy macrophages. Growth on lower energy intakes combined with reduced duodenal lipid storage suggests dietary fat is stored in the gut and is not available as an energy source."

Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Lipid profile in pediatric and adult patients with lysosomal acid lipase deficiency treated with sebelipase alfa: longitudinal evidence from the International LAL-D Registry. (PubMed, Atherosclerosis) - "In patients with LAL-D not receiving lipid-modifying medication, sebelipase alfa treatment improved lipid abnormalities, with sustained reductions of LDL-C and triglycerides and elevations of HDL-C."

Journal • Dyslipidemia • Metabolic Disorders • Pediatrics

LIVER INJURY IN CHILDREN WITH LYSOSOMAL ACID LIPASE DEFICIENCY: AN ANALYSIS OF THE INTERNATIONAL LAL-D REGISTRY (ESPGHAN 2026) - "Conclusions Signs of liver injury were present in most children with LAL-D regardless of genotype and were a major factor contributing to diagnosis. Sebelipase alfa treatment is associated with reduced transaminase levels."

Clinical • Dyslipidemia • Fibrosis • Hepatology • Hypertriglyceridemia • Immunology • Liver Failure • Metabolic Disorders • Rare Diseases

Cascade Screening Uncovers Lysosomal Acid Lipase Deficiency in Two Adult Sisters: Early Diagnosis Improves Outcomes (ENDO 2026) - "Initially diagnosed with Familial Hypercholesterolemia, she was treated with atorvastatin 40 mg...She began sebelipase alfa 2 enzyme therapy and after 12 months of therapy, liver enzymes normalized (ALT 22 U/L, ALT 20 U/L)... These cases highlight the importance of considering LAL-D in adults with hypercholesterolemia and unexplained liver enzyme elevations, particularly when hepatomegaly is present. Cascade screening can identify affected relatives, enabling timely diagnosis. Early initiation of enzyme replacement therapy offers significant hepatic and metabolic benefits, as demonstrated by normalization of liver enzymes and further LDL-C reduction in both patients."

Clinical • Dyslipidemia • Familial Hypercholesterolemia • Fibrosis • Genetic Disorders • Hepatology • Immunology • Metabolic Disorders

Assessment of liver injury and genotype among children and adults with lysosomal acid lipase deficiency: analysis of the international LAL D registry (EASL 2026) - " Children and adults enrolled in the International LAL-D Registry were included regardless of treatment status with sebelipase alfa (LAL enzyme replacement therapy [ERT])... Across LIPA genotypes, liver damage was a common feature of LAL-D among pediatric and adult patients; children typically present with elevated transaminases. ERT was associated with improvements in transaminase levels."

Clinical • Dyslipidemia • Fibrosis • Hepatology • Immunology • Inflammation • Liver Failure • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Real-World Study of Management and Outcomes of Patients with Lysosomal Acid Lipase Deficiency (LAL-D) in France. (PubMed, Adv Ther) - "This descriptive study based on claims data confirmed the severity of LAL-D and the need to define the best management, considering the heterogeneity of the patients."

Journal • Real-world evidence • Cardiovascular • Dyslipidemia • Fibrosis • Hepatology • Hypertension • Immunology • Liver Failure • Lysosomal Storage Diseases • Metabolic Disorders • Portal Hypertension • Rare Diseases

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