Clinical UM Guideline

 

Subject: Sebelipase alfa (KANUMA™)
Guideline #: CG-DRUG-111 Publish Date:    09/20/2018
Status: New Last Review Date:    07/26/2018

Description

This document addresses the use of sebelipase alfa (KANUMA, Alexion Pharmaceuticals Inc., Cheshire, CT), a hydrolytic lysosomal cholesteryl ester and triacylglycerol-specific enzyme administered intravenously for the treatment of the rare disease lysosomal acid lipase deficiency (LAL-D), also known as Wolman disease (WD) and cholesteryl ester storage disease (CESD). WD is an early onset form of LAL-D that is seen in infants and CESD another form of LAL-D with a later onset, seen in early childhood or later in life.

Clinical Indications

Medically Necessary:

  1. Initial treatment with sebelipase alfa is considered medically necessary when used for the treatment of individuals less than 4 years of age when the following criteria are met:
    1. Individual has a diagnosis of LAL-D disorder (also known as WD); and
    2. Diagnosis has been confirmed by one of the following:
      1. A dried blood spot test demonstrating deficient lysosomal acid lipase activity; or
      2. Documented molecular genetic test revealing mutations in the lipase A, lysosomal acid type (LIPA) gene; or
  2. Initial treatment with sebelipase alfa is considered medically necessary when used for the treatment of individuals 4 years of age and older when all the following criteria are met:
    1. Individual has a diagnosis of LAL-D disorder (also known as CESD); and
    2. Diagnosis has been confirmed by one of the following:
      1. A dried blood spot test demonstrating deficient lysosomal acid lipase activity; or
      2. Documented molecular genetic test revealing mutations in the LIPA gene; and
    3. Individual has a baseline alanine aminotransferase (ALT) level greater than or equal to 1.5 times the upper limit of normal.

Maintenance therapy with sebelipase alfa for ongoing treatment of lysosomal acid lipase (LAL) disorder is considered medically necessary when the following criteria are met:

  1. Individual previously met criteria for initial therapy; and
  2. Documentation of clinical improvement in symptoms or lab values is provided.

Not Medically Necessary:

The use of sebelipase alfa is considered  not medically necessary for all other indications not listed above as medically necessary.

Coding

The following codes for treatments and procedures applicable to this guideline are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

HCPCS

 

J2840

Injection, sebelipase alfa, 1 mg [KANUMA]

 

 

ICD-10 Diagnosis

 

 

E75.5

Other lipid storage disorders (Wolman’s disease)

 

E75.6

Lipid storage disorder, unspecified

 

Discussion/General Information

LAL-D is a rare autosomal recessive metabolic disease that ranges in severity and age of onset. Infants with a rapidly progressive form of LAL-D, also known as WD, rarely survive beyond 1 year of age and are believed to have complete loss of lysosomal acid lipase. The later-onset forms, associated with partial enzyme loss, are collectively known as CESD which present in childhood with lipid abnormalities, elevated liver enzymes, and enlargement of the liver and spleen. It is estimated that WD affects approximately 1-2 infants per million births, and CESD affects 25 individuals per million births, but may be as high as 1 in 40,000. Most patients present before 5 years of age. Hepatomegaly and splenomegaly are common. Serum transaminases and lipids are often elevated. Gastrointestinal symptoms are present in approximately one-third of cases. Two-thirds of patients have liver fibrosis. In older individuals, progression of the disease leads to cirrhosis and early atherosclerotic cardiovascular disease.

Sebelipase alfa was granted priority review by the U.S. Food and Drug Administration (FDA) and received breakthrough therapy designation on December 8, 2015 as the first enzyme replacement therapy (ERT) developed to help break down cholesteryl ester and triacylglycerol-specific enzyme indicated for individuals diagnosed with LAL-D. Previous treatments focused on management of symptoms caused by the disease and included diet modifications, cholesterol medications, and liver or stem cell transplants.

The FDA approval is based on data from two studies which met their primary endpoints, the Acid Lipase Replacement Investigating Safety and Efficacy trial (ARISE) and LAL-CL03 trial, in addition to a supporting open-label extension study (LAL-CL01/CL04) that included infant, pediatric and adult participants with confirmed LAL-D. Results from the LAL-CL03 study indicated significant benefit in terms of survival (6 of 9 participants, or 67%) in individuals with infant form of LAL-D beyond 12 months of age, compared with 0 of 21 participants in an untreated historical cohort. Treatment with sebelipase alfa also led to a larger reduction from baseline in ALT values and liver fat content versus the placebo.

In 2015, Burton and colleagues reported findings from the ARISE trial, a multicenter, phase 3 randomized controlled trial that evaluated safety and effectiveness of ERT in participants 4 years or older with LAL-D (known as CESD) with sebelipase alfa (n=36) administered intravenously every other week compared to placebo infusion (n=30). Additional study inclusion criteria included confirmed enzyme activity and ALT at least 1.5 upper limits of normal range. In conclusion the authors found that:

At 20 weeks, the alanine aminotransferase level was normal in 11 of 36 patients (31%) in the sebelipase alfa group and in 2 of 30 (7%) in the placebo group (P=0.03), with mean changes from baseline of −58 U per liter versus −7 U per liter (P<0.001). With respect to prespecified key secondary efficacy end points, we observed improvements in lipid levels and reduction in hepatic fat content (P<0.001 for all comparisons, except P=0.04 for triglycerides). The number of patients with adverse events was similar in the two groups; most events were mild and were considered by the investigator to be unrelated to treatment.

Study results found that infusion with sebelipase alfa therapy “resulted in a reduction in multiple disease-related hepatic and lipid abnormalities in children and adults with lysosomal acid lipase deficiency”.

Sebelipase alfa (KANUMA) 2015 FDA Product Information label includes the following contraindications, warnings, precautions and adverse events:

Contraindications:

Warning and Precautions:
Hypersensitivity reactions including anaphylaxis:

Hypersensitivity to eggs or egg products:

Adverse Reactions

References

Peer Reviewed Publications:

  1. Balwani M, Breen C, Enns GM, et al. Clinical effect and safety profile of recombinant human lysosomal acid lipase in patients with cholesteryl ester storage disease. Hepatology. 2013; 58(3):950-957.
  2. Burton BK, Blawani M, Feillet F, et al. A phase 3 trial of sebelipase alfa in lysosomal acid lipase deficiency. N Engl J Med. 2015; 373:1010-1020.
  3. Hamilton J, Jones I, Srivastava R, Galloway P. A new method for the measurement of lysosomal acid lipase in dried blood spots using the inhibitor Lalistat 2. Clinica Chimica Acta. 2012; 413(15-16):1207-1210.
  4. Jones SA, Rojas-Caro S Quinn AG, et al. Survival in infants treated with sebelipase alfa for lysosomal acid lipase deficiency: an open-label, multicenter, dose-escalation study. Orphanet J Rare Dis. 2017; 12(1):25.
  5. Reiner Z, Guardamagna O, Nair D, et al. Lysosomal acid lipase deficiency- an under recognized cause of dyslipaemia and liver dysfunction.. Atherosclerosis. 2014; 235:21-30.
  6. Valayannopoulos V, Malinova V, Honzik T, et al. Sebelipase alfa over 52 weeks reduced serum transaminases, liver volume and improves serum lipids in patients with lysosomal acid lipase deficiency. J hepatol. 2014; 61(5):1135-1142.
  7. Zhang B, Porto AF. Cholesteryl ester storage disease: protean presentations of lysosomal acid lipase deficiency. J Pediatr Gastroenterol Nutr. 2013; 56(6):682.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. Alexion Pharmaceuticals. An extended access protocol for sebelipase alfa for patients with lysosomal acid lipase deficiency. NLM Identifier: NCT02376751. Last updated: June 6, 2016. Available at: https://clinicaltrials.gov/ct2/show/NCT02376751?term=sebelipase+alfa+AND+lysosomal+acid+lipase+deficiency&rank=6. Accessed on May 14, 2018.
  2. Alexion Pharmaceuticals. A multicenter study of SBC-102 (sebelipase alfa) in patients with lysosomal acid lipase deficiency ARISE (ACID Lipase Replacement Investigating Safety and Efficacy). NLM Identifier: NCT01757184. Last updated: March 20, 2017. Available at: https://clinicaltrials.gov/ct2/show/NCT01757184. Accessed on May 14, 2018.
  3. Alexion Pharmaceuticals. Trial in children with growth failure due to early onset lysosomal acid lipase (LAL) deficiency/Wolman disease. NLM Identifier: NCT01371825. Last updated: November 14, 2017. Available at: https://clinicaltrials.gov/ct2/show/NCT01371825?term=LAL-CL03&rank=1. Accessed on May 14, 2018.
  4. Kanuma [Product Information], Cheshirt, CT. Alexion Pharmaceuticals Inc.; December 8, 2015. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/125561s000lbl.pdf. Accessed on May 14, 2018.
  5. National Institute of Health. National Centers for Aging Translation Services. Genetic and Rare Diseases Information Center (GARD). Lysosomal acid lipase deficiency. Last updated April 2, 2016. Available at: https://rarediseases.info.nih.gov/gard/12097/lysosomal-acid-lipase-deficiency/resources/1. Accessed on May 14, 2018.
  6. Sebelipase alfa (systemic). In: DrugPoints® System (electronic version). Truven Health Analytics, Greenwood Village, CO. Updated April 30, 2018. Available at: http://www.micromedexsolutions.com. Accessed on May 14, 2018.
  7. Sebelipase alfa Monograph. Lexicomp® Online, American Hospital Formulary Services® (AHFS®) Online, Hudson, Ohio, Lexi-Comp., Inc. Last revised March 22, 2017. Accessed on May 14, 2018.
Websites for Additional Information
  1. National Institute of Neurological Disorders and Stroke. NINDS acid lipase disease information page. Last updated December 17, 2017. Available at: https://www.ninds.nih.gov/Disorders/All-Disorders/Acid-Lipase-Disease-Information-Page. Accessed on May 14, 2018.
  2. National Organization for Rare Diseases. Available at: https://rarediseases.org/for-patients-and-families/information-resources/rare-disease-information/. Accessed on May 14, 2018.
Index

Cholesteryl ester storage disease
Enzyme replacement therapy
KANUMA
Lysosomal acid lipase deficiency
Sebelipase alfa
Wolman disease

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

History

Status

Date

Action

New

07/26/2018

Medical Policy & Technology Assessment Committee (MPTAC) review. Initial document development.  Moved content of DRUG.00093 Sebelipase alfa (KANUMA™) to new clinical utilization management guideline document with the same title.