CENTENE

Corporation

Clinical Policy: Elapegademase-lvlr (Revcovi)
Reference Number: CP.PHAR.419
Effective Date: 04.23.19
Last Review Date: 05.26
Line of Business: Commercial, HIM/ICHRA, Medicaid

Coding Implications
Revision Log

See Important Reminder at the end of this policy for important regulatory and legal
information.

Description

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

B. Other diagnoses/indications (must meet 1 or 2):

1. 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/ICHRA)
   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/ICHRA, and CP.PMN.255 for Medicaid; or

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b. For drugs NOT on the formulary (commercial, health insurance
marketplace/ICHRA) 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/ICHRA, and CP.PMN.16 for Medicaid; or

2. 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/ICHRA, and CP.PMN.53 for Medicaid.

II. Continued Therapy

A. Adenosine Deaminase Severe Combined Immunodeficiency Disease (must meet all):

1. 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);

B. Other diagnoses/indications (must meet 1 or 2):

1. 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/ICHRA)
   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/ICHRA, and CP.PMN.255 for Medicaid; or
   b. For drugs NOT on the formulary (commercial, health insurance
   marketplace/ICHRA) 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/ICHRA, and CP.PMN.16 for Medicaid; or
2. 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/ICHRA, and CP.PMN.53 for Medicaid.

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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/ICHRA, and
CP.PMN.53 for Medicaid, or evidence of coverage documents.

IV.Appendices/General Information

Appendix A: Abbreviation/Acronym Key

ADA-SCID: adenosine deaminase
severe combined immune deficiency
disease
dATP: deoxyadenosine triphosphate
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

• 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:
○ Adagen-naïve patients: every 4 - 8 weeks for up to 1 year, and every 3 - 6 months

 thereafter

○ 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.

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Improvement in the general clinical status of the patient may be gradual (as evidenced by
improvement in various clinical parameters) but should be apparent by the end of the first
year of therapy.

V. Dosage and Administration

VI.Product Availability

Single-dose vial: 2.4 mg/1.5 mL (1.6 mg/mL)

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Coding Implications

Codes referenced in this clinical policy are for informational purposes only. Inclusion or
exclusion of any codes does not guarantee coverage. Providers should reference the most up-to-
date sources of professional coding guidance prior to the submission of claims for
reimbursement of covered services.

Reviews, Revisions, and Approvals

Important Reminder

This clinical policy has been developed by appropriately experienced and licensed health care
professionals based on a review and consideration of currently available generally accepted
standards of medical practice; peer-reviewed medical literature; government agency/program
approval status; evidence-based guidelines and positions of leading national health professional
organizations; views of physicians practicing in relevant clinical areas affected by this clinical
policy; and other available clinical information. The Health Plan makes no representations and
accepts no liability with respect to the content of any external information used or relied upon in
developing this clinical policy. This clinical policy is consistent with standards of medical
practice current at the time that this clinical policy was approved. “Health Plan” means a health
plan that has adopted this clinical policy and that is operated or administered, in whole or in part,
by Centene Management Company, LLC, or any of such health plan’s affiliates, as applicable.

The purpose of this clinical policy is to provide a guide to medical necessity, which is a
component of the guidelines used to assist in making coverage decisions and administering

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benefits. It does not constitute a contract or guarantee regarding payment or results. Coverage
decisions and the administration of benefits are subject to all terms, conditions, exclusions, and
limitations of the coverage documents (e.g., evidence of coverage, certificate of coverage, policy,
contract of insurance, etc.), as well as to state and federal requirements and applicable Health
Plan-level administrative policies and procedures.

This clinical policy is effective as of the date determined by the Health Plan. The date of posting
may not be the effective date of this clinical policy. This clinical policy may be subject to
applicable legal and regulatory requirements relating to provider notification. If there is a
discrepancy between the effective date of this clinical policy and any applicable legal or
regulatory requirement, the requirements of law and regulation shall govern. The Health Plan
retains the right to change, amend or withdraw this clinical policy, and additional clinical
policies may be developed and adopted as needed, at any time.

This clinical policy does not constitute medical advice, medical treatment, or medical care. It is
not intended to dictate to providers how to practice medicine. Providers are expected to exercise
professional medical judgment in providing the most appropriate care, and are solely responsible
for the medical advice and treatment of members. This clinical policy is not intended to
recommend treatment for members. Members should consult with their treating physician in
connection with diagnosis and treatment decisions.

Providers referred to in this clinical policy are independent contractors who exercise independent
judgment and over whom the Health Plan has no control or right of control. Providers are not
agents or employees of the Health Plan.

This clinical policy is the property of the Health Plan. Unauthorized copying, use, and
distribution of this clinical policy or any information contained herein are strictly prohibited.
Providers, members, and their representatives are bound to the terms and conditions expressed
herein through the terms of their contracts. Where no such contract exists, providers, members
and their representatives agree to be bound by such terms and conditions by providing services to
members and/or submitting claims for payment for such services.

Note:
For Medicaid members, when state Medicaid coverage provisions conflict with the coverage
provisions in this clinical policy, state Medicaid coverage provisions take precedence. Please
refer to the state Medicaid manual for any coverage provisions pertaining to this clinical policy.