Aetna Commercial Clinical Policy

Aetna Retifanlimab-dlwr (Zynyz) Form

Effective Date

07/01/2023

Last Reviewed

11/13/2023

Original Document

  Reference



Background for this Policy

U.S. Food and Drug Administration (FDA)-Approved Indications

Merkel Cell Carcinoma

Zynyz is indicated for the treatment of adult patients with metastatic or recurrent locally advanced Merkel cell carcinoma (MCC).

Retifanlimab-dlwr is available as Zynyz (Incyte Corporation) and is a programmed death receptor-1 (PD-1)-blocking antibody. Retifanlimab-dlwr binds to the PD-1 receptor and blocks PD-L1 and PD-L2 interaction which potentiates T-cell activity with resultant inhibition of T-cell proliferation and cytokine production. Additionally, upregulation of PD-1 ligands occurs in some tumors, and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors (Incyte, 2023).

According to the prescribing information, Zynyz carries the following warnings and precautions:

Immune-mediated adverse reactions

  • Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, including the following: immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis, immune-mediated endocrinopathies, immune-mediated nephritis with renal dysfunction, and immune-mediated dermatologic adverse reactions, and solid organ transplant rejection.
  • Monitor for early identification and management. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment.
  • Withhold or permanently discontinue Zynyz and administer corticosteroids based on the severity of reaction.
  • Infusion-related reactions: Interrupt, slow the rate of infusion, or permanently discontinue Zynyz based on severity of reaction.
  • Complications of allogeneic HSCT: Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after being treated with a PD-1/PD-L1–blocking antibody.
  • Embryo-fetal toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and use of effective contraception.

    • Per the prescribing information for Zynyz, the most common (≥10%) adverse reactions are fatigue, musculoskeletal pain, pruritis, diarrhea, rash, pyrexia, and nausea.

    Merkel cell carcinoma (MCC) is a rare form of skin cancer that is aggressive and can metastasize to other areas of the body. An estimated 60% of MCC tumors are found in men. As of 2015, an estimated 2,500 individuals per year are diagnosed with this cancer in the United States. The incidence of MCC is approximately 0.7 people per 100,000 people in the general United States population. It dramatically increases to an estimated 9.8 people per 100,000 in individuals more than 85 years of age (NORD, 2023).

    On March 22, 2023, the U.S. Food and Drug Administration granted accelerated approval to retifanlimab-dlwr (Zynyz) for the treatment of adult patients with metastatic or recurrent locally advanced Merkel cell carcinoma (MCC). The FDA approval was based on data from the POD1UM-201 trial.

    The POD1UM-201 trial, an open-label, multiregional, single-arm study, evaluated the safety and efficacy of Zynyz for 65 patients with metastatic or recurrent locally advanced MCC who had not received prior systemic therapy for their advanced disease. Patients received Zynyz 500 mg intravenously every 4 weeks until disease progression, unacceptable toxicity, or up to 24 months. Tumor response assessments were performed every 8 weeks for the first year of therapy and 12 weeks thereafter. The major efficacy outcome measures were objective response rate (ORR) and duration of response (DOR) assessed by an independent central review committee according to RECISTv1.1. The ORR was 52% (95% confidence interval [CI]: 40, 65) with complete response rate of 18%. Twenty-six patients (76%) had a DOR ≥ 6 months and 21 (62%) had a DOR ≥ 12 months. Safety was evaluated for 105 patients with MCC and the most common (≥10%) adverse reactions were fatigue, musculoskeletal pain, pruritus, diarrhea, rash, pyrexia, and nausea. Serious adverse reactions occurred in 22% of patients receiving Zynyz (FDA, 2023; Incyte, 2023).

    Note

    : Requires Precertification:

    Precertification of retifanlimab-dlwr (Zynyz) is required of all Aetna participating providers and members in applicable plan designs. For precertification of retifanlimab-dlwr (Zynyz), call (866) 752-7021 (commercial), or fax (888) 267-3277. For Statement of Medical Necessity (SMN) precertification forms, see

    Specialty Pharmacy Precertification

    .

    For Medicare Part B plans, call (866) 503-0857, or fax (844) 268-7263.

    Note

    : Site of Care Utilization Management Policy applies. For information on site of service for

    retifanlimab-dlwr (Zynyz)

    , see

    Utilization Management Policy on Site of Care for Specialty Drug Infusions

    .

    Exclusions

    Aetna will not provide coverage for members who have experienced disease progression while on PD-1 or PD-L1 inhibitor therapy.

    Criteria for Initial Approval

    Merkel Cell Carcinoma (MCC)

    Aetna considers retifanlimab-dlwr (Zynyz) medically necessary for treatment of metastatic or recurrent locally advanced MCC.

    Aetna considers all other indications as experimental and investigational.

    Continuation of Therapy

    Aetna considers continuation of retifanlimab-dlwr (Zynyz) therapy (up to 24 months total) medically necessary in members requesting reauthorization for an indication listed in Section II when there is no evidence of unacceptable toxicity or disease progression while on the current regimen..

    Dosage and Administration

    Retifanlimab-dlwr is supplied as Zynyz 500 mg/20 mL (25 mg/mL) solution in a single-dose vial for intravenous infusion.

    Merkel cell carcinoma:

    The recommended dosage of Zynyz is 500 mg administered as an intravenous infusion over 30 minutes every 4 weeks until disease progression, unacceptable toxicity, or up to 24 months. Administer Zynyz as an intravenous infusion after dilution.

    Refer to the full prescribing information for Zynyz for dosage modifications for adverse reactions and preparation and administration instructions.

    Source: Incyte, 2023