Long-term survival with sebelipase alfa enzyme replacement therapy in infants with rapidly progressive lysosomal acid lipase deficiency: final results from 2 open-label studies

Vijay, Suresh; Brassier, Anaïs; Ghosh, Arunabha; Fecarotta, Simona; Abel, Florian; Marulkar, Sachin; Jones, Simon A.

doi:10.1186/s13023-020-01577-4

Cited by 25 publications

(42 citation statements)

References 15 publications

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“…Most of our patients (4/5) experienced no medically relevant infusion-associated reaction (IAR) during the follow up, thus confirming the acceptable safety profile of the product [ 17 ]. One patient had one medically relevant IAR justifying systematic infusion premedication.The anaphylactic reaction presented by the patient might be favored by the absence of sebelipase alfa titration (i. e. the patient received a 5 mg/kg sebelipase alfa infusion as first dose compared to progressive increase of the dose for the 4 other patients).…”

Section: Discussionsupporting

confidence: 62%

“…WD is an ultrarare disease leading to death before 12 months of age if untreated [ 8 ]. Sebelipase alfa ERT trials reported 68% survival at 5 years [ 17 ] but long-term follow-up in real-life settings are lacking. Here, we report the bio-clinical evolution of 5 WD patients treated with sebelipase alfa up to 10 years and we confirm its strong efficacy.…”

Section: Discussionmentioning

confidence: 99%

“…All patients presented with strongly abolished LIPA activity and clinical manifestations before one month of age. DNA sequence analysis demonstrated 3 pathogenic variants (c.260G>T [ 5 , 10 , 17 , 20 , 21 ], c.481delA [ 22 ], c.676-2A>G [ 10 , 23 ]) reported in patients presenting with LALD. LIPA variants of Patient 1 (c.538G>A) and Patient 3 (c.429-1G>C) were previously published in LAL-CL03 trial [ 16 , 17 ] and in a large-scale screening of LALD in at risk population [ 24 ], respectively.…”

Section: Discussionmentioning

confidence: 99%

“…After one year, patients exhibited improvement in weight, gastrointestinal symptoms, and markers of liver dysfunction. A mid-term follow-up of these patients, and a second trial including 10 patients (LAL-CL08), was recently published [ 17 ]. The median age of surviving patients was 5.2 years and 3.2 years in the two trials, respectively.…”

Section: Introductionmentioning

confidence: 99%

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Sebelipase alfa enzyme replacement therapy in Wolman disease: a nationwide cohort with up to ten years of follow-up

Demaret

Lacaille

Wicker

et al. 2021

Orphanet J Rare Dis

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Background Wolman disease (WD), the rapidly progressive phenotype of lysosomal acid lipase (LAL) deficiency, presents in neonates with failure to thrive and hepatosplenomegaly, and leads to multi-organ failure and death before 12 months of age. In clinical trials, enzyme replacement therapy (ERT) with sebelipase alfa led to improved survival, growth and biological parameters in WD patients followed up to 5 years. Long-term follow-up and health-related quality of life (HRQoL) evaluation are lacking. Results We performed a nationwide, retrospective study of sebelipase alfa in WD patients. Five patients with abolished LAL activity and bi-allelic LIPA mutations were included with a median follow-up of 7 years (1–10). ERT was initiated at a median age of 1 month (0–4). Infusion tolerance was excellent on the long-term with only one patient requiring systematic pre-medication. Cholestyramine, fat-soluble vitamin supplements and a specific diet (high in medium-chain triglycerides and low in long-chain fatty acids) were prescribed. Liver function tests, plasma lipid profiles, fat-soluble vitamin levels and growth parameters improved. Three patients transiently exhibited a neuromyopathic phenotype (footdrop gait, waddling walk or muscle fatigue) but electromyography and muscle strength testing were normal. At last follow-up, all patients were alive with normal growth parameters and a satisfactory HRQoL, no patient had special education needs, and one patient required parenteral nutrition since an acute gastroenteritis. Conclusions Early ERT initiation allowed 100% survival with positive outcomes. Very long-term follow-up and hematopoietic stem cell transplantation while on ERT should be evaluated to strengthen the benefits of sebelipase alfa.

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Section: Discussionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sebelipase alfa enzyme replacement therapy in Wolman disease: a nationwide cohort with up to ten years of follow-up

Demaret

Lacaille

Wicker

et al. 2021

Orphanet J Rare Dis

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“…In our analysis for liver volume change, the overall pooled reduction was not statistically significant; however, all three individual studies have reported a significant decline with the sebelipase intervention. 15,16,18 Here too, Jones et al…”

Section: Change In Other Efficacy Measuresmentioning

confidence: 98%

Enzyme replacement therapy in lysosomal acid lipase deficiency (LAL-D): a systematic literature review

Bashir

Tiwari

Duseja

2021

Therapeutic Advances in Rare Disease

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Background: Lysosomal acid lipase deficiency (LAL-D) is a very rare genetic abnormality caused by LIPA gene mutation. The disease has two distinct clinical variants in humans: Wolman disease in infants and cholesteryl ester storage disease in children and adults. Both conditions are characterized by elevated serum transaminases, dyslipidaemia, severe liver steatosis and accelerated fibrosis or cirrhosis, contributing to its high rate of early mortality. Recently sebelipase alfa (recombinant human LAL) was launched to address its underlying pathology. This systematic review evaluates the safety and efficacy of sebelipase alfa for LAL-D. Methods: This systematic review was performed following the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Clinical trial records were systematically searched in PubMed/Medline, ClinicalTrials.gov ., Cochrane Library and Google Scholar up to September 2020. Records that have reported at least one of the included outcomes were included. Baseline and endpoint mean and standard deviation (SD) for all outcomes were recorded. For safety, frequency and overall distribution of different adverse events were included. Results: A total of seven records from five individual studies with 110 LAL-D patients were included into this study. The mean age ranged from 2.57 months in infants to 31.6 years among adults. Serum transaminases (alanine aminotransferase and aspartate aminotransferase), serum lipids (total cholesterol, triglycerides, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol), gamma-glutamyl transferase and liver volume were included as efficacy outcomes. Final pooled results were synthesized as a change from baseline to end of the treatment. A significant effect on both serum transaminases and other serum lipid was achieved ( p < 0.01), while non-significant differences were seen for GGT and liver volume as p = 0.35 and p = 0.08 was observed. Mostly the adverse events related to the infusions were infrequent and mild-to-moderate in severity. Conclusion: Sebelipase alfa as an enzyme replacement provides an effective, safe and well tolerated treatment in both variants of LAL-D. Plain language summary A systematic literature review on safety and efficacy of enzyme replacement therapy in lysosomal acid lipase deficiency Lysosomal acid lipase deficiency (LAL-D) is a rare, progressive, genetic disorder caused by functional mutations in the LIPA gene, which encodes LAL enzyme. This enzyme maintains lipid homeostasis by hydrolysing the cholesterol esters and triglycerides. Patients with deficient LAL activity are seen with abnormal liver functions which keep them at a high risk of early mortality. Clinical diagnosis of this disease is very challenging due to both its low prevalence and low awareness among patients/clinicians and additionally due to its overlap with other liver/lipid disorders. Also, owing to lack of safe and effective treatment, dietary modifications and some lipid modifying drugs are usually used to control the LAL-D manifestations. Recently, recombinant human LAL named as sebelipase alfa (Kanuma™, Alexion Pharmaceuticals, Inc., New Haven, Connecticut, USA) was approved in 2015 for the European Union and subsequently in the United States as an enzyme replacement therapy for LAL deficiency. The initial clinical trial data indicate that sebelipase alfa produces a significant improvement in all of the wide range of LAL-D manifestations. However, the cumulative evidence is not reported regarding its safety and effective use. Therefore, a systematic literature review of all the clinical trial records by following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines was undertaken. From all of the available clinical trial records, 110 LAL-D patients treated with sebelipase alfa were included. Serum transaminases, serum lipids, gamma-glutamyl transferase (GGT) and liver volume were included as efficacy outcomes. Final pooled results were synthesized as a change from baseline to end of the treatment. A significant effect on both serum transaminases and other serum lipids was achieved ( p < 0.01), while non-significant differences were observed for GGT and liver volume, with p = 0.35 and p = 0.08 respectively. Mostly the adverse events related to the infusions were infrequent and mild-to-moderate in severity. The enzyme replacement provides an effective, safe and well tolerated treatment in both variants of LAL-D.

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Rapid whole‐genome sequencing leading to specific treatment for two infants with haemophagocytic lymphohistiocytosis due to Wolman disease

Selvanathan

Forwood

Russell

et al. 2023

Pediatric Blood & Cancer

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Long-term survival with sebelipase alfa enzyme replacement therapy in infants with rapidly progressive lysosomal acid lipase deficiency: final results from 2 open-label studies

Cited by 25 publications

References 15 publications

Sebelipase alfa enzyme replacement therapy in Wolman disease: a nationwide cohort with up to ten years of follow-up

Sebelipase alfa enzyme replacement therapy in Wolman disease: a nationwide cohort with up to ten years of follow-up

Enzyme replacement therapy in lysosomal acid lipase deficiency (LAL-D): a systematic literature review

Rapid whole‐genome sequencing leading to specific treatment for two infants with haemophagocytic lymphohistiocytosis due to Wolman disease

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