Niraparib (Zejula) Form

Niraparib (Zejula®) is a poly(ADP-ribose) polymerase (PARP) inhibitor. FDA Approved Indication(s) Zejula is indicated for: • Maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to first-line platinum- based chemotherapy • Maintenance treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for Zejula 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 Zejula is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Ovarian Cancer (must meet all):

1. Diagnosis of epithelial ovarian, fallopian tube, or primary peritoneal cancer;
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. For brand Zejula requests, member must use generic niraparib, if available, unless contraindicated or clinically significant adverse effects are experienced;

2. Member meets one of the following (a or b): a. Both i and ii: i. Newly diagnosed stage II-IV disease; ii. Completed first-line platinum-based chemotherapy regimen and is in a complete or partial response;
   b. Both i and ii (see Appendix F): i. Documentation of deleterious or suspected deleterious germline BRCA- mutation as confirmed on a CLIA approved diagnostic test (see Appendix D); ii. Completed platinum-based chemotherapy and is in a complete or partial response; Page 1 of 9

   CLINICAL POLICY Niraparib

3. Zejula is prescribed in one of the following ways (a or b): a. As a single agent; b. In combination with bevacizumab for platinum-sensitive persistent disease or recurrence for one of the following (i or ii): i. Radiographic and/or clinical relapse in members with previous complete remission and relapse after ≥ 6 months after completing prior chemotherapy; ii. Immediate treatment for serially rising CA-125 in members that previously received chemotherapy;
4. Member has not previously received a PARP inhibitor (e.g., Lynparza®, Rubraca®, Talzenna®);
5. Request meets one of the following (a or b): a. Dose does not exceed any of the following (i or ii): i. 300 mg per day; ii. 3 capsules or tablets per day; b. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN
   Approval duration:
   Medicaid/HIM – 6 months Commercial – 12 months or duration of request, whichever is less B. Other diagnoses/indications (must meet 1 or 2):
6. 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
7. 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. Ovarian Cancer (must meet all):
8. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Zejula for a covered indication and has received this medication for at least 30 days;

9. If request is for use in an adult member with advanced HRD positive ovarian cancer after > 3 lines of chemotherapy, provider attestation of acknowledgement for Page 2 of 9

   CLINICAL POLICY Niraparib withdrawal of this indication due to risk of detrimental effect on overall survival (OS) in patients who used Zejula (see Appendix E);

10. If request is for use in an adult member with non-germline BRCA mutated platinum sensitive recurrent ovarian cancer in the second or later line maintenance setting, provider attestation of acknowledgement for possible OS detriment with Zejula use in this population (see Appendix F);
11. Member is responding positively to therapy;
    
    5. For brand Zejula requests, member must use generic niraparib, if available, unless contraindicated or clinically significant adverse effects are experienced;
    6. If request is for a dose increase, request meets one of the following (a or b): a. New dose does not exceed any of the following (i or ii): i. 300 mg per day; ii. 3 capsules or tablets per day; b. New dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN
       Approval duration:
       Medicaid/HIM – 12 months Commercial – 12 months or duration of request, whichever is less B. Other diagnoses/indications (must meet 1 or 2):
12. 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

13. 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 2 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 3 of 9

    CLINICAL POLICY Niraparib IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key FDA: Food and Drug Administration HRD: homologous recombination deficiency
    OS: overall survival PARP: poly(ADP-ribose) polymerase PFS: progression free survival Appendix B: Therapeutic Alternatives This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent and may require prior authorization.
    Drug Name Dosing Regimen Dose Limit/ Maximum Dose Ovarian Cancer Alimta® (pemetrexed) Alkeran® (melphalan) Avastin® (bevacizumab)
    carboplatin (Paraplatin®) cisplatin (Platinol-AQ®) cyclophosphamide (Cytoxan®) docetaxel (Taxotere®) doxorubicin (Doxil®, Adriamycin®) etoposide (Vepesid®) gemcitabine (Gemzar®) ifosfamide (Ifex®) irinotecan (Camptosar®) oxaliplatin (Eloxatin®) topotecan (Hycamtin®) Hexalen® (altretamine) Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. Various Various Various Various Various Various Various Various Various Various Various Various Various Various Various Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Varies Appendix C: Contraindications/Boxed Warnings None reported Appendix D: General Information • There are insufficient data regarding the use of consecutive PARP inhibitors. Most PARP inhibitor pivotal trials excluded prior PARP inhibitor use, the NCCN does not make any explicit recommendations (other than for ovarian cancer, where they state data is limited), and there are no randomized controlled trials evaluating such use.
    • Clinical trials utilized Myriad BRACAnalysis CDx to detect the presence of deleterious or suspected deleterious germline BRCA mutations in blood samples from patients with ovarian, fallopian tube, and primary peritoneal cancer. Additional information on FDA- approved companion diagnostic tests is available at http://www.fda.gov/companiondiagnostics. Page 4 of 9

    CLINICAL POLICY Niraparib Appendix E: Withdrawal of Advanced HRD Ovarian Cancer After > 3 Lines of Chemotherapy Indication • GlaxoSmithKline, manufacturer of Zejula, voluntarily withdrew Zejula’s FDA-approved indication for the treatment of adult patients with advanced ovarian, fallopian tube, or primary peritoneal cancer who have been treated with 3 or more prior chemotherapy regimens and whose cancer is associated with homologous recombination deficiency (HRD) positive status. The withdrawal became effective as of September 14, 2022 and does not affect other indications for Zejula. • The decision was made in consultation with the FDA and based on totality of information from PARP inhibitors in the late line treatment setting in ovarian cancer. A potential detrimental effect on OS was observed with other (non-GlaxoSmithKline) PARP inhibitors in two independent randomized, active-controlled clinical trials conducted in a BRCA mutant 3L + advanced ovarian cancer population. • The approval of Zejula for this indication was based on the QUADRA study (NCT02354586), a single-arm study which evaluated the safety and efficacy of niraparib for this indication. The results from the QUADRA study (single arm, uncontrolled nature) offered no comparative OS information, which made it difficult to “assess any potential effect on Zejula on time to event endpoints.” • Physicians should not initiative new treatment with Zejula in the treatment indication of adult patients with advanced ovarian cancer, fallopian tube, or primary peritoneal cancer who have been treated with 3 or more prior chemotherapy regimens and whose cancer is associated with HRD positive status.
    Appendix F: Restricted Second or Later Line Setting Indication to Germline BRCA Mutated Population
    • GlaxoSmithKline, manufacturer of Zejula, restricted the indication of Zejula for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy received in the second or later line setting to the germline BRCA-mutated patient population only in the United States. • The decision was made at the request of the FDA following the final OS analysis of the NOVA (NCT01847274) study. The observed OS results from NOVA study are shown: o Germline BRCA-mutated cohort (N = 203): median OS was 43.6 months for patients with Zejula compared to 41.6 months for patients on placebo (HR = 0.93 [95% CI 0.63, 1.36]) o Non-germline BRCA-mutated cohort (N = 350): median OS was 31.3 months for patients treated with Zejula compared to 41.6 months for patients on placebo (HR = 1.10 [95% CI 0.83, 1.46]) o Non-germline BRCA-mutated, HRD positive subgroup: median OS was 37.3 months for patients treated with Zejula compared to 41.4 months for patients on placebo (HR = 1.32 [95% CI 0.84, 2.06]) • The current OS results indicate possible OS detriment to patients in the overall non- germline BRCA-mutated cohort and to patients in the non-germline BRCA-mutated/HRD positive subgroup who received Zejula maintenance in this setting compared to placebo.
    • Physicians who are currently treating patients with Zejula for patients with non-germline BRCA-mutated platinum sensitive recurrent ovarian cancer in the second or later line Page 5 of 9

    CLINICAL POLICY Niraparib maintenance setting are asked to discuss this information with those patients for an individual benefit-risk assessment so that they can make an informed decision regarding their ongoing care. V. Dosage and Administration
    Indication Ovarian, fallopian tube, or primary peritoneal cancer VI. Product Availability
    Capsule: 100 mg Tablet: 100 mg, 200 mg, 300 mg Dosing Regimen 300 mg PO QD Maximum Dose 300 mg/day VII.