REVCOVI, Elapegademase-lvlr Form

Elapegademase-lvlr (Revcovi®) is a recombinant adenosine deaminase.
FDA Approved Indication(s) Revcovi is indicated for the treatment of adenosine deaminase severe combined immune deficiency disease (ADA-SCID) in pediatric and adult patients. Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria. It is the policy of health plans affiliated with Centene Corporation® that Revcovi is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Adenosine Deaminase Severe Combined Immune Deficiency Disease (must meet all):

1. Diagnosis of ADA-SCID confirmed by genetic testing;
   2. Prescribed by or in consultation with an immunologist or hematologist;
   3. Member has failed bone marrow transplantation or is not a candidate for bone marrow transplantation;
2. Dose does not exceed 0.4 mg/kg per week. Approval duration:
   Medicaid/HIM – 6 months Commercial – 6 months or to the member’s renewal date, whichever is longer B. Other diagnoses/indications (must meet 1 or 2):

3. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or Page 1 of 6

   CLINICAL POLICY Elapegademase-lvlr

4. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
   II. Continued Therapy A. Adenosine Deaminase Severe Combined Immunodeficiency Disease (must meet all):
5. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
6. Member is responding positively to therapy (see Appendix D for examples);
   3. If request is for a dose increase, new dose does not exceed 0.4 mg/kg per week.
      Approval duration:
      Medicaid/HIM – 12 months
      Commercial – 6 months or to the member’s renewal date, whichever is longer B. Other diagnoses/indications (must meet 1 or 2):
7. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

8. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
   III. Diagnoses/Indications for which coverage is NOT authorized:
   A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid, or evidence of coverage documents. Page 2 of 6

   CLINICAL POLICY Elapegademase-lvlr IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key ADA-SCID: adenosine deaminase severe combined immune deficiency disease dAXP: deoxyadenosine nucleotides FDA: Food and Drug Administration Appendix B: Therapeutic Alternatives
   Not applicable Appendix C: Contraindications/Boxed Warnings None reported Appendix D: General Information
   • Examples of positive response to therapy include improvement in immune function (T cell, B cell, and natural killer lymphocytes), reduction in frequency/severity of opportunistic infections, and decrease from baseline or maintenance of normal red cell dATP levels. • Once treatment with Revcovi has been initiated, a target trough plasma ADA activity should be at least 30 mmol/hr/L. In order to determine an effective dose of Revcovi, trough plasma ADA activity (pre-injection) should be determined every 2 weeks for Adagen-naïve patients and every 4 weeks for patients previously receiving Adagen therapy, during the first 8 - 12 weeks of treatment, and every 3 - 6 months thereafter. A decrease of ADA activity below this level suggests noncompliance to treatment or a development of antibodies (anti-drug, anti-PEG, and neutralizing antibodies). Antibodies to Revcovi should be suspected if a persistent fall in pre-injection levels of trough plasma ADA activity below 15 mmol/hr/L occurs. In such patients, testing for antibodies to Revcovi should be performed. If a persistent decline in trough plasma ADA activity occurs, immune function and clinical status should be monitored closely and precautions should be taken to minimize the risk of infection. If antibodies to Revcovi are found to be the cause of a persistent fall in trough plasma ADA activity, then adjustment in the dosage of Revcovi and other measures may be taken to induce tolerance and restore adequate ADA activity.
   • Two months after starting Revcovi treatment, trough erythrocyte deoxyadenosine nucleotide (dAXP) levels should be maintained below 0.02 mmol/L, and monitored at least twice a year.
   • The degree of immune function may vary from patient to patient. Each patient will require appropriate monitoring consistent with immunologic status. Total and subset lymphocytes should be monitored periodically as follows:
   o Adagen-naïve patients: every 4 - 8 weeks for up to 1 year, and every 3 - 6 months thereafter
   • o Other patients: every 3 - 6 months
   Immune function, including the ability to produce antibodies, generally improves after 2 - 6 months of therapy, and matures over a longer period. In general, there is a lag between the correction of the metabolic abnormalities and improved immune function. Improvement in the general clinical status of the patient may be gradual (as evidenced by Page 3 of 6

   CLINICAL POLICY Elapegademase-lvlr improvement in various clinical parameters) but should be apparent by the end of the first year of therapy. V. Dosage and Administration
   Maximum Dose 0.4 mg/kg/week Indication ADA-SCID Dosing Regimen Patients transitioning from Adagen® to Revcovi:
   If the weekly Adagen dose is unknown, or if the weekly Adagen dose is at or lower than 30 U/kg, use Revcovi 0.2 mg/kg IM weekly. If the weekly Adagen dose is > 30 U/kg, an equivalent weekly Revcovi dose (mg/kg) should be calculated by dividing the Adagen dose in U/kg by 150. Subsequent doses may be increased by increments of 0.033 mg/kg weekly if trough ADA activity is under 30 mmol/hr/L, trough dAXPs are above 0.02 mmol/L, and/or the immune reconstitution is inadequate based on the clinical assessment of the patient. The total weekly dose may be divided into multiple IM administrations during a week.
   Adagen-naïve patients:
   0.2 mg/kg IM twice a week based on ideal body weight or actual weight whichever is greater for at least 12-24 weeks until immune reconstitution is achieved. Dose may be gradually adjusted down to maintain trough ADA activity over 30 mmol/hr/L, trough dAXP level under 0.02 mmol/L, and/or to maintain adequate immune reconstitution based on clinical assessment of the patient. VI. Product Availability
   Single-dose vial: 2.4 mg/1.5 mL (1.6 mg/mL) VII.