Lantidra (donislecel-jujn)

Lantidra (donislecel-jujn) is an allogeneic pancreatic islet cellular therapy that contains insulin-producing beta cells derived from donated pancreases. It is indicated for adult patients with Type 1 diabetes who have difficulty achieving target HbA1c levels due to recurrent severe hypoglycemic episodes, despite intensive diabetes management with insulin, devices, and education.

Lantidra (donislecel-jujn) aims to restore endogenous insulin production and normalize blood glucose levels. The treatment involves intravenous infusion of the drug, which contains immunoisolated allogeneic islets, followed by immunosuppression to prevent graft rejection.

In clinical trials, Lantidra (donislecel-jujn) allowed some patients to achieve insulin independence for over 1 year. It is particularly beneficial for those with hypoglycemia unawareness, as it reduces reliance on exogenous insulin to control blood glucose.

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Limitations include lack of evidence showing benefit in well-controlled Type 1 diabetes, as well as potential risks from the infusion procedure and long-term immunosuppression. There is also no evidence to support use in patients with liver disease, kidney failure, or kidney transplants.

Definitions

• Allogeneic refers to cells, tissues, or organs sourced from a genetically distinct individual of the same species.
• Beta Cells are insulin-producing cells found in the pancreas that regulate blood glucose levels.
• C-peptide is a protein fragment released during the conversion of insulin, often used as a marker of endogenous insulin production.
• Diabetic Ketoacidosis (DKA) is a serious complication of diabetes caused by very low insulin levels leading to high blood sugar, ketone production, and acidosis.
• HbA1c (Glycated Hemoglobin) is a measure used to determine average blood glucose levels over a period of several months.
• Hypoglycemia Unawareness is a condition where individuals don't experience the typical symptoms of low blood sugar, which can lead to severe hypoglycemia.
• Hypoglycemia is a condition characterized by abnormally low levels of blood sugar.
• Immunoisolated Allogeneic Islets are pancreatic islet cells derived from a donor and shielded to reduce the risk of immune rejection when transplanted.
• Immunosuppression is the act of reducing or inhibiting the body's immune response, often to prevent rejection of transplanted organs or cells.
• Intraportal Islet Cell Infusion is the process of introducing isolated islet cells directly into the portal vein of the liver, a common site for islet transplantation.
• Pancreatic Islet Cellular Therapy is a treatment approach where insulin-producing cells from the pancreas are transplanted into a patient to replace deficient or non-functioning cells.

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Medical Necessity Criteria for Initial Authorization

The Plan considers Lantidra (donislecel-jujn) medically necessary when ALL of the following criteria are met:

1. Prescribed by or in consultation with an endocrinologist experienced in the management of type 1 diabetes and familiar with the risks and monitoring requirements of Lantidra therapy; AND
2. Administered by a healthcare provider experienced in performing intraportal islet cell infusion (e.g., interventional radiologists and surgeons); AND
3. The member is 18 years of age or older; AND
4. The member has a confirmed diagnosis of type 1 diabetes for at least 5 years; AND
5. The member has evidence of intensive diabetes management, defined as:
   • a. Self-monitoring of glucose values at least 3 times per day on average; and
   • b. Using insulin pump therapy or at least 3 insulin injections per day; and
   • c. Under the care of a diabetes specialist with at least 3 evaluations in the past 12 months;
   AND
6. The member is exhibiting ONE of the following, despite intensive insulin management efforts:
   • a. hypoglycemic unawareness, as defined by inability to sense hypoglycemia until the blood glucose falls to less than 54 mg/dL; or
   • b. TWO (2) or more episodes of severe hypoglycemia, defined as an event with symptoms consistent with hypoglycemia in which the patient requires the assistance of another person and which is associated with a blood glucose below 54 mg/dL; or
   • c. TWO (2) or more hospital visits for diabetic ketoacidosis over the last year; or
   AND
7. The member has not achieved HbA1c target goals set by their diabetes care team with current treatment regimens; AND
8. The member is willing and able to adhere to required monitoring and immunosuppression post-infusion; AND
9. The member does NOT have ANY of the following:
   • a. Active infection including hepatitis C, hepatitis B, HIV; and/or
   • b. Concomitant diseases or conditions, including pregnancy, that contraindicate the procedure for donislecel infusion or immunosuppression; and/or
   • c. C-peptide response to glucagon stimulation >0.3 ng/mL; and/or
   • d. History of non-adherence to prescribed regimens; and/or
   • e. Liver disease, renal failure, or who have received a renal transplant.

Severe Coexisting Cardiac Disease

Characterized by any one of the following conditions:

1. Recent myocardial infarction within the past 6 months; and/or
2. Angiographic evidence of non-correctable coronary artery disease; and/or
3. Evidence of ischemia on a functional cardiac exam; and/or
4. Left ventricular ejection fraction less than 30%; and/or

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Initial authorization is for no more than one infusion.

If the above prior authorization criteria are met, Lantidra (donislecel-jujn) will be authorized for one infusion.

Medical Necessity Criteria for Reauthorization

Reauthorization for one additional infusion (up to a lifetime limit of 3 total infusions) will be granted if the member meets ALL of the following:

1. The member continues to meet all applicable Initial Criteria; AND
2. The member requires a second or third infusion due to loss of islet graft function; AND
3. The member responded to the prior infusion with sustained C-peptide production and/or periods of exogenous insulin independence; AND
4. Additional authorization is for no more than one infusion, with a lifetime limit of 3 total infusions.

Experimental or Investigational / Not Medically Necessary

Lantidra (donislecel-jujn) for any other indication or use is considered not medically necessary by the Plan, as it is deemed to be experimental, investigational, or unproven. Non-covered indications include, but are not limited to, the following:

• Complications of diabetes like diabetic neuropathy, nephropathy, and retinopathy
• In pediatric patients with type 1 diabetes
• More than three infusions of Lantidra (donislecel-jujn)
• Pancreatic cancer, i.e. managing diabetes resulting after pancreatectomy for pancreatic tumors
• Patients whose diabetes is well-controlled with insulin therapy
• Patients with hypoglycemic unawareness who can prevent repeated severe hypoglycemic events using intensive diabetes management
• Patients with liver disease, renal failure, or history of kidney transplantation
• Patients without diabetes who have hypoglycemia due to other conditions
• Type 2 diabetes