ENDARI (l-glutamine oral powder)

ENDARI (l-glutamine oral powder)

Self-Administration (powder for oral solution)

Diagnosis considered for coverage:

• Endari is an amino acid indicated to reduce the acute complications of sickle cell disease in adult and pediatric patients 5 years of age and older.

Coverage Criteria:

For diagnosis of sickle cell disease:

• Dose does not exceed recommended weight-based dosing (see below); AND
  • Less than 30 kg (60 lbs) – 5 gm twice daily (10 mg total per day)
  • 30 kg to 65 kg (66 lbs to 143 lbs) – 10 gm twice daily (20 mg total per day)
  • More than 65 kg (143 lbs) – 15 gm twice daily (30 mg total per day)
• Patient is 5 years of age or older; AND
• Prescribed by or in consultation with a hematologist or oncologist; AND
• Diagnosis of sickle cell disease or sickle β^o-thalassemia is supported by medical records; AND
• Trial and failure, contraindication, or intolerance to hydroxyurea therapy; AND
• Medical records support that the patient has had 2 or more painful sickle cell crises within the past 12 months requiring visits to an emergency room or medical facility.

Reauthorization Criteria:

For diagnosis of sickle cell disease:

• Dose does not exceed recommended weight-based dosing; AND
• Documentation of positive clinical response to therapy (e.g., a reduction in the number of sickle cell crises, lower incidence of acute chest syndrome, etc.).

Coverage Duration:

• Initial: 1 year
• Reauthorization: 1 year

Authorization is not covered for the following:

• The use of this drug for indications not listed in this policy does not meet the coverage criteria established by the Western Health Advantage (WHA) Pharmacy and Therapeutics (P&T) Committee.

Additional Information:

• The mechanism of action of the amino acid L-glutamine in treating sickle cell disease is not fully understood. In general, Endari works to increase the amount of free glutamine circulating in the blood. Sickle cells can take up this free glutamine and use it to generate anti-oxidant molecules. These new antioxidants can help neutralize the oxidative stress in sickle cells. This can allow them to regain the flexibility necessary to travel through blood vessels and capillaries, carrying oxygen to tissues throughout the body.
• The clinical studies enrolled 110 pediatric patients in the following age groups: 46 children (5 years up to less than 12 years) and 64 adolescents (12 years to less than 17 years). The safety and effectiveness of Endari in pediatric patients with sickle cell disease younger than 5 years old has not been established.
• A sickle cell crisis was defined by the Endari Clinical Trial in Sickle Cell Disease as a visit to an emergency room/medical facility for sickle cell disease-related pain which was treated with a parenterally administered (e.g., IV, SC) narcotic or parenterally administered ketorolac. In addition, the occurrence of chest syndrome, priapism, and splenic sequestration were considered sickle cell crises.
• Endari should be mixed immediately before ingestion with 8 oz. (240 mL) of a cold or room temperature beverage such as water, milk, or apple juice, or 4 to 6 oz. of food such as applesauce or yogurt.

Policy Updates:

02/15/2022 – New policy approved by P&T.

References:

1. Centers for Disease Control and Prevention (CDC) Web site. https://www.cdc.gov/ncbddd/sicklecell/facts.html. Updated October 21, 2019. Accessed February 3, 2020.
2. Department of Health and Human Services. National Institutes of Health. National Heart, Lung, and Blood Institute. Evidence-based management of sickle cell disease. Expert panel report, 2014. https://www.nhlbi.nih.gov/sites/default/files/media/docs/sickle-cell-disease-report%20020816_0.pdf. Accessed February 3, 2020.
3. Endari [package insert], Torrance, CA: Emmaus Medical, Inc.; October 2020.
4. FDA Briefing Document Oncologic Drugs Advisory Committee Meeting. L-glutamine. https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM559734.pdf. Accessed February 3, 2020.
5. Niihara Y, Macan H, Eckman JR, et al. L-glutamine therapy reduces hospitalization for sickle cell anemia and sickle β0-thalassemia patients at six months – A Phase II randomized trial. Clin Pharmacol Biopharm. 2014;3(1):116.
6. Niihara Y, Miller ST, Kanter J, et al. A Phase 3 trial of L-glutamine in sickle cell disease. N Engl J Med. 2018;379(3):226-235.
7. Pironi L, Arends J, Bozzetti F, et al. ESPEN guidelines on chronic intestinal failure in adults. Clin Nutr. 2016;35:247-307.
8. Rees DC, Williams TN, Gladwin MT. Sickle-cell disease. Lancet. 2010; 376:2018.