Teplizumab (PRV-031) Form

Teplizumab-mzwv (Tzield™) is a CD3-directed antibody. FDA Approved Indication(s) Tzield is indicated to delay the onset of Stage 3 type 1 diabetes (T1D) in adults and pediatric patients aged 8 years and older with Stage 2 T1D. 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 Tzield is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Delayed Onset of Stage 3 Type 1 Diabetes (must meet all):

1. Diagnosis of Stage 2 T1D as evidenced by all of the following (a, b, and c): a. Presence of 2 or more diabetes-related autoantibodies detected in 2 samples obtained within the last 6 months: anti-insulin autoantibodies (mIAA), islet cell antibodies (ICA), anti-glutamic acid decarboxylase(GAD)65ab, anti-ICA512ab; b. Abnormal glucose tolerance during an oral glucose-tolerance test (OGTT) confirmed within the last 7 weeks (i, ii, or iii) (two confirmatory tests are required for members age ≥ 18 years): i. Fasting plasma glucose ≥ 110 mg/dL, and < 126 mg/dL; ii. 2 hour plasma glucose ≥ 140 mg/dL, and < 200 mg/dL; iii. 30, 60, or 90 minute value on OGTT ≥ 200 mg/dL; c. Member does not have symptoms of diabetes (e.g., polyuria, polydipsia, polyphagia);
2. Prescribed by or in consultation with an endocrinologist;
   3. Age ≥ 8 years;
   4. Member does not have a diagnosis of Stage 3 T1D or type 2 diabetes;
   5. Member has a first, second, or third degree relative who was diagnosed with T1D before age 40 and started on insulin therapy within one year of diagnosis;

3. Documentation of member’s current body surface area (BSA) (m2);

   7. Dose does not exceed a total of 11,240 mcg/m2 administered over a 14-day treatment course (see section V). Approval duration: 3 months (one 14-day treatment course only) Page 1 of 6

   CLINICAL POLICY Teplizumab-mzwv B. Other diagnoses/indications (must meet 1 or 2):

4. 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
5. 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. Delayed Onset of Stage 3 Type 1 Diabetes
6. Continued therapy will not be authorized as Tzield is indicated to be administered as a one-time treatment course only. Approval duration: Not applicable 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 – Page 2 of 6

   CLINICAL POLICY Teplizumab-mzwv CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid, or evidence of coverage documents; B. Stage 3 or 4 T1D; C. Type 2 diabetes. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key BSA: body surface area FDA: Food and Drug Administration GAD: glutamic acid decarboxylase ICA: islet cell antibodies Appendix B: Therapeutic Alternatives
   Not applicable Appendix C: Contraindications/Boxed Warnings None reported Appendix D: General Information • There are 4 recognized stages of T1D: mIAA: anti-insulin autoantibodies OGTT: oral glucose tolerance test T1D: type 1 diabetes
   • o Stage 1: ≥ 2 diabetes-related autoantibodies, normoglycemia, presymptomatic o Stage 2: ≥ 2 diabetes-related autoantibodies, dysglycemia, presymptomatic o Stage 3: ≥ 2 diabetes-related autoantibodies, dysglycemia, symptomatic o Stage 4: longstanding T1D In 2010, teplizumab failed to meet the primary efficacy endpoint (a composite of total daily insulin usage and HbA1c level at 12 months) in the phase 3 Protégé study, demonstrating no difference compared to placebo for the treatment of patients with early- onset T1D; as a result, clinical programs were suspended. In 2018, Provention Bio acquired teplizumab from MacroGenics/Lilly. A new phase 3 study for the treatment of early-onset T1D was completed (PROTECT, NCT03875729). Results from this study are not yet available.
   V. Dosage and Administration Indication Delayed onset of Stage 3 T1D Dosing Regimen 14 day treatment course administered IV QD: • Day 1: 65 mcg/m2 • Day 2: 125 mcg/m2 • Day 3: 250 mcg/m2 • Day 4: 500 mcg/m2 • Days 5-14: 1,030 mcg/m2 Maximum Dose 11,240 mcg/m2/ treatment course . VI. Product Availability Single-dose vial: 2 mg/mL
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   CLINICAL POLICY Teplizumab-mzwv VII.