Kanuma® (sebelipase alfa) is an innovative enzyme therapy approved for the treatment of patients with lysosomal acid lipase deficiency (LAL-D).1 Kanuma is approved in the United States, European Union and Japan.
LAL-D is a genetic and progressive ultra-rare metabolic disease associated with multi-organ damage in infant, pediatric and adult patients and premature death in infants.1 In patients with LAL-D, genetic mutations result in decreased or loss in activity of the LAL enzyme, leading to continuous accumulation of cholesteryl esters and triglycerides in the liver, blood vessel walls and other tissue. This can result in progressive complications in multiple organs, including the liver, spleen, and intestine.2,3
LAL-D affects patients of all ages with clinical manifestations from infancy through adulthood and may have sudden and unpredictable clinical complications.
Without treatment, infants with LAL-D can face rapid disease progression over a period of weeks that is typically fatal within a matter of months. The median age of death in these patients is 3.7 months (range 1.4 to 46.3 months).4 Pediatric and adult patients with LAL-D face substantial disease burden.
Approximately 50% of children and adults with LAL-D progress to fibrosis, cirrhosis, or liver transplant within 3 years of clinical manifestation onset.5 The median age of onset in children and adults with LAL-D is 5.8 years (range 0 to 42 years).6 LAL-D can be diagnosed with a simple blood test.7
Treating Patients Who Have LAL-D with Kanuma
Kanuma is the first approved treatment for patients with LAL-D. It is administered via intravenous infusion. In a clinical study, 67% of infants (6 of 9) with LAL-D (patients who presented with rapidly progressive disease within the first 6 months of life) who were treated with Kanuma survived beyond 12 months of age compared with 0% of untreated infants (0 of 21) in a historical cohort, all of whom died by 8 months of age.1
In a clinical study of 66 pediatric and adult patients with LAL-D, patients treated with Kanuma had larger reductions from baseline in ALT values and liver fat content, as measured by MRI, compared to patients treated with placebo. Reduced ALT values were generally seen within two weeks. The significance of these findings as they relate to progression of liver disease in LAL-D has not been established. In addition, treated patients had significant improvements in lipid parameters, including LDL-c, triglycerides, and HDL-c, compared to placebo. The effect of Kanuma on cardiovascular morbidity and mortality has not been established.1
IMPORTANT SAFETY INFORMATION FOR KANUMA
Indications and Usage
KANUMA® is indicated for the treatment of patients with a diagnosis of lysosomal acid lipase deficiency (LAL-D).
WARNINGS AND PRECAUTIONS
Hypersensitivity Reactions Including Anaphylaxis
Hypersensitivity reactions, including anaphylaxis, have been reported in KANUMA-treated patients. In clinical trials, 3 of 106 (3%) patients treated with KANUMA experienced signs and symptoms consistent with anaphylaxis. These patients experienced reactions during infusion with signs and symptoms including chest discomfort, conjunctival injection, dyspnea, generalized and itchy rash, hyperemia, swelling of eyelids, rhinorrhea, severe respiratory distress, tachycardia, tachypnea, and urticaria. Anaphylaxis has occurred as early as the sixth infusion and as late as 1 year after treatment initiation.
In clinical trials, 21 of 106 (20%) KANUMA-treated patients, including 9 of 14 (64%) infants and 12 of 92 (13%) pediatric patients, 4 years and older, and adults experienced signs and symptoms either consistent with or that may be related to a hypersensitivity reaction. Signs and symptoms of hypersensitivity reactions, occurring in two or more patients, included abdominal pain, agitation, fever, chills, diarrhea, eczema, edema, hypertension, irritability, laryngeal edema, nausea, pallor, pruritus, rash, and vomiting. The majority of reactions occurred during or within 4 hours of the completion of the infusion. Patients were not routinely pre-medicated prior to infusion of KANUMA in these clinical trials.
Due to the potential for anaphylaxis, appropriate medical support should be readily available when KANUMA is administered.
Hypersensitivity to Eggs or Egg Products
Consider the risks and benefits of treatment in patients with known systemic hypersensitivity reactions to eggs or egg products.
The most common adverse reactions are: In Patients with Rapidly Progressive Disease Presenting within the First 6 Months of Life (≥30%): diarrhea, vomiting, fever, rhinitis, anemia, cough, nasopharyngitis, and urticaria. In Pediatric and Adult Patients (≥8%): headache, fever, oropharyngeal pain, nasopharyngitis, asthenia, constipation, and nausea.
Kanuma [package insert]. New Haven, CT: Alexion Pharmaceuticals, Inc; 2015.
Bernstein DL,Hülkova H, Bialer G, Desnick R. Chloesteryl ester storage disease: review of the findings in 135 reported patients with an underdiagnosed disease. J Hepatol. 2013;58:1230-43. doi:10.1016/j.jhep.2013.02.014.
Reiner Z, Guardamagna O, Nair D, et al. Lysosomal acid lipase deficiency – an under-recognized cause of dyslipidemia and liver dysfunction. Atherosclerosis. 2014;235:21-30. doi:10.1016/j.atherosclerosis.2014.04.003.
Jones SA, Valayannopoulos V, Schneider E, et al. Rapid progression and mortality of lysosomal acid lipase deficiency presenting in infants. Genet Med. 2016;18(5):452-458. doi: 10.1038/gim.2015.108.
Data on file. Alexion Pharmaceuticals, Inc. 2015.
Burton BK, Deegan PB, Enns GM, et al. Clinical Features of Lysosomal Acid Lipase Deficiency. J Pediatr Gastroenterol Nutr. 2015;61(6):619-25. doi: 10.1097/MPG.0000000000000935.
Hamilton J, Jones I, Srivastana R, Galloway P. A new method for the measurement of lysosomal acid lipase in dried blood spots using the inhibitor Lalistat 2. Clin Chim Acta. 2012;413:1207-10. doi:10.1016/j.cca.2012.03.019.