ZYNYZ

Patient Terms and Conditions: Update effective as of January 1, 2024. Patients must have minimum out-of-pocket costs of $15.01 to redeem this offer. Annual benefit maximum applies, as may other restrictions. Patients will be responsible for any out-of-pocket costs above the maximum annual program benefit. Program benefit applies to medication cost only and does not cover any costs to administer the medication. Offer with program member number is valid through December 31 of the year of issue. On January 1 of the following year, the offer automatically resets and is subject to annual limits if the prescription benefit remains the same. Patients must have commercial prescription benefit coverage. Offer is not valid if a patient is uninsured, is paying cash for the treatment, or is covered by an Alternate Funding Program (AFP). Offer is not valid if a patient is enrolled in a federal or state prescription program (including Medicare Part B, Medicare Advantage, Medicaid, TRICARE, or any state medical or pharmaceutical assistance program). Patient enrollment in a copay adjustment program, such as a maximizer or accumulator program, may impact the value of this offer. If patients move or switch from commercial prescription benefit coverage to any government prescription benefit coverage, they will no longer be eligible. This offer is not insurance. Offer is valid only for an FDA-approved or compendia-recognized use. Patients are responsible for reporting receipt of program benefits to any commercial insurer that pays for or reimburses any part of the prescriptions filled with this program to the extent required by law or by the insurer. Patients agree not to seek reimbursement from their insurer or any other third party for all or any part of the benefit received through this offer. This offer may not be sold, purchased, traded, or transferred and is void if reproduced. Use of this offer does not obligate the patient to use or continue to use ZYNYZ® (retifanlimab-dlwr). No other purchase and no refills are necessary. This offer is limited to one (1) per person during this offering period. Patient is responsible for all taxes. There are no membership fees associated with this program. Offer is good only in the United States and Puerto Rico and is void where prohibited or otherwise restricted by law. Incyte Corporation reserves the right to rescind, revoke, or amend this program without notice. If questions arise, please call 1-855-452-5234.

Provider Terms and Conditions: Update effective as of January 1, 2024. Patients must have minimum out-of-pocket costs of $15.01 to redeem this offer. Annual benefit maximum applies, as may other restrictions. Patients will be responsible for any out-of-pocket costs above the maximum annual program benefit. Program benefit applies to medication cost only and does not cover any costs to administer the medication. Offer with program member number is valid through December 31 of the year of issue. On January 1 of the following year, the offer automatically resets and is subject to annual limits if the prescription benefit remains the same. Patients must have commercial prescription benefit coverage. Offer is not valid if a patient is uninsured, is paying cash for the treatment, or is covered by an Alternate Funding Program (AFP). In order to receive the program benefits, the patient or provider must submit an Explanation of Benefits (EOB) form or a Remittance Advice (RA) form. The submitted form must include the primary insurance plan information, primary insurance payment, procedure codes, NDC, and date of service. All documentation (EOB, RA) must be submitted within 180 days of receiving each dose. Offer is not valid if a patient is enrolled in a federal or state prescription program (including Medicare Part B, Medicare Advantage, Medicaid, TRICARE, or any state medical or pharmaceutical assistance program). Patient enrollment in a copay adjustment program, such as a maximizer or accumulator program, may impact the value of this offer. If your patients move or switch from commercial prescription benefit coverage to any government prescription benefit coverage, they will no longer be eligible. This offer is not insurance. Offer is valid only for an FDA-approved or compendia-recognized use. You are responsible for reporting redemption of assistance under this program to any commercial insurer that pays for or reimburses any part of the prescriptions filled with this program to the extent required by law or by the insurer. You agree not to seek reimbursement from the insurer or any other third party for all or any part of the benefit received through this offer. You must comply with the patient’s insurer’s policies in requesting payment from Incyte and disclose the coinsurance assistance to the payor as necessary. If your patient uses this offer, you must process the claim for ZYNYZ® (retifanlimab-dlwr) in accordance with your usual reimbursement formula without increasing the price or altering the reimbursement formula or otherwise charging a premium for ZYNYZ. You may not use this savings program to promote or market your practice’s services. Offer is good only in the United States and Puerto Rico and is void where prohibited or otherwise restricted by law. This offer may not be sold, purchased, traded, or transferred. Use of this offer does not obligate the patient to use or continue to use ZYNYZ. No other purchase and no refills are necessary. This offer is limited to one (1) per person during this offering period and is not transferable. Patient is responsible for all taxes. There are no membership fees associated with this program. Incyte Corporation reserves the right to rescind, revoke, or amend this program without notice. If you have any questions, please call 1-866-420-7693.

INDICATIONS AND USAGE

ZYNYZ is a programmed death receptor-1 (PD-1)–blocking antibody indicated for the treatment of adult patients with metastatic or recurrent locally advanced Merkel cell carcinoma.

This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

IMPORTANT SAFETY INFORMATION

Severe and Fatal Immune-Mediated Adverse Reactions

Important immune-mediated adverse reactions listed may not be inclusive of all possible severe and fatal immune-mediated reactions.

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, can occur at any time after starting or discontinuing treatment with a PD-1/PD-L1–blocking antibody, and can affect more than one body system simultaneously.

Monitor patients closely for symptoms and signs that may be clinical manifestations of such reactions. Early identification and management of immune‐mediated adverse reactions are essential to ensure safe use of PD-1/PD-L1–blocking antibodies. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. If suspected, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue ZYNYZ depending on severity. In general, if ZYNYZ requires interruption or discontinuation, administer systemic corticosteroid therapy (1-2 mg/kg/day prednisone or equivalent) until improvement to ≤ Grade 1. Then, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose adverse reactions are not controlled with corticosteroids.

Immune-Mediated Pneumonitis

ZYNYZ can cause immune-mediated pneumonitis. Immune-mediated pneumonitis occurred in 3% (13/440) of patients, including fatal (0.2%), Grade 3 (0.9%), and Grade 2 (1.4%) reactions. Pneumonitis led to permanent discontinuation of ZYNYZ in 1 patient and withholding in 0.9%.

Systemic corticosteroids were required in 77% (10/13) of patients. Pneumonitis resolved in 10 of the 13 patients.

Immune-Mediated Colitis

ZYNYZ can cause immune-mediated colitis. Cytomegalovirus infections/reactivations have occurred in patients with corticosteroid-refractory immune-mediated colitis treated with PD-1/PD-L1–blocking antibodies. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies.

Immune-mediated colitis occurred in 1.6% (7/440) of patients, including Grade 4 (0.2%), Grade 3 (0.2%), and Grade 2 (0.7%). Colitis led to permanent discontinuation of ZYNYZ in 1 patient and withholding in 0.9%.

Systemic corticosteroids were required in 71% (5/7) of patients. Colitis resolved in 4/7 patients.

Immune-Mediated Hepatitis

ZYNYZ can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 3% (13/440) of patients, including Grade 4 (0.2%), Grade 3 (2.3%), and Grade 2 (0.5%). Hepatitis led to permanent discontinuation of ZYNYZ in 1.4% of patients and withholding in 0.9%.

Systemic corticosteroids were required in 85% (11/13) of patients. Hepatitis resolved in 6/13 patients.

Immune-Mediated Endocrinopathies

Adrenal Insufficiency

ZYNYZ can cause primary or secondary adrenal insufficiency. For ≥ Grade 2 adrenal insufficiency, initiate symptomatic treatment per institutional guidelines, including hormone replacement as clinically indicated. Withhold or permanently discontinue ZYNYZ depending on severity.

Adrenal insufficiency occurred in 0.7% (3/440) of patients, including Grade 3 (0.5%) and Grade 2 (0.2%). ZYNYZ was permanently discontinued in no patients and was withheld for 1 patient with adrenal insufficiency.

All patients required systemic corticosteroids. Adrenal insufficiency resolved in 1 of the 3 patients.

Hypophysitis

ZYNYZ can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field cuts, and can cause hypopituitarism. Initiate hormone replacement as clinically indicated. Withhold or permanently discontinue ZYNYZ depending on severity.

Hypophysitis occurred in 0.5% (2/440, both Grade 2) of patients. No patients discontinued or withheld ZYNYZ due to hypophysitis.

All patients required systemic steroids. Hypophysitis resolved in 1 of the 2 patients.

Thyroid Disorders

ZYNYZ can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement or medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue ZYNYZ depending on severity.

Thyroiditis occurred in 0.7% (3/440, all Grade 1) of patients. No patients discontinued or withheld ZYNYZ due to thyroiditis. Thyroiditis resolved in 1 of the 3 patients.

Hypothyroidism

Hypothyroidism occurred in 10% (42/440) of patients receiving ZYNYZ, including Grade 2 (4.8%). No patients discontinued due to hypothyroidism. ZYNYZ was withheld in 0.5% of patients.

Systemic corticosteroids were required for 1 patient, and 79% (33/42) of patients received endocrine therapy.

Hyperthyroidism

Hyperthyroidism occurred in 6% (24/440) of patients receiving ZYNYZ, including Grade 2 (2.5%). ZYNYZ was not discontinued in any patient and was withheld in 1 patient. Systemic corticosteroids were required for 13% (3/24) of patients, and 46% (11/24) of patients received endocrine therapy.

Type 1 Diabetes Mellitus, Which Can Present with Diabetic Ketoacidosis

Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold ZYNYZ depending on severity.

Type 1 diabetes mellitus occurred in 0.2% (1/440) of patients, including Grade 3 (0.2%) adverse reactions.

Immune-Mediated Nephritis with Renal Dysfunction

ZYNYZ can cause immune-mediated nephritis. Immune-mediated nephritis occurred in 1.6% (7/440) of patients receiving ZYNYZ, including Grade 4 (0.5%), Grade 3 (0.7%), and Grade 2 (0.5%). Nephritis led to permanent discontinuation of ZYNYZ in 0.9% of patients and withholding in 1 patient.

Systemic corticosteroids were required in 57% (4/7) of patients. Nephritis resolved in 3/7 patients.

Immune-Mediated Dermatologic Adverse Reactions

ZYNYZ can cause immune-mediated rash or dermatitis. Bullous and exfoliative dermatitis, including Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms, and toxic epidermal necrolysis, has occurred with PD-1/PD-L1–blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes. Withhold or permanently discontinue ZYNYZ depending on severity.

Immune-mediated skin reactions occurred in 8% (36/440) of patients, including Grade 3 (1.1%) and Grade 2 (7%). Immune-mediated dermatologic adverse reactions led to permanent discontinuation of ZYNYZ in 1 patient and withholding in 2.3% of patients.

Systemic corticosteroids were required in 25% (9/36) of patients. Immune-mediated dermatologic adverse reactions resolved in 75% (27/36) of patients.

Other Immune-Mediated Adverse Reactions

The following clinically significant immune-mediated adverse reactions occurred at an incidence of < 1% in 440 patients who received ZYNYZ or were reported with the use of other PD-1/PD-L1–blocking antibodies, including severe or fatal cases.

Cardiac/vascular: myocarditis, pericarditis, vasculitis

Gastrointestinal: pancreatitis, to include increases in serum amylase and lipase levels, gastritis, duodenitis

Musculoskeletal: myositis/polymyositis, rhabdomyolysis (and associated sequelae, including renal failure), arthritis, polymyalgia rheumatica

Neurological: meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy

Ocular: uveitis, iritis, and other ocular inflammatory toxicities. Some cases can be associated with retinal detachment. Various grades of visual impairment to include blindness can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada–like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss.

Endocrine: hypoparathyroidism

Other (Hematologic/Immune): hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection, other transplant (including corneal graft) rejection.

Infusion-Related Reactions

A severe infusion-related reaction (Grade 3) occurred in 1 (0.2%) of 440 patients. Monitor patients for signs and symptoms; interrupt or slow the rate of infusion or permanently discontinue ZYNYZ based on severity of reaction. Consider premedication with an antipyretic and/or an antihistamine for patients who have had previous systemic reactions to infusions of therapeutic proteins.

Complications of Allogeneic HSCT

Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/PD-L1–blocking antibody. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause), which may occur despite intervening therapy between PD-1/PD-L1 blockade and allogeneic HSCT.

Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1/PD-L1–blocking antibody prior to or after an allogeneic HSCT.

Embryo-Fetal Toxicity

ZYNYZ can cause fetal harm when administered to a pregnant woman. Animal studies have demonstrated that inhibition of the PD-1/PD-L1 pathway can lead to increased risk of immune-mediated rejection of the developing fetus, resulting in fetal death. Advise women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for 4 months after the last dose.

Lactation

Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for 4 months after the last dose.

Adverse Reactions

The safety of ZYNYZ was evaluated in 105 patients with metastatic or recurrent locally advanced MCC.

Serious adverse reactions occurred in 22% of patients receiving ZYNYZ. The most frequent serious adverse reactions (≥ 2% of patients) were fatigue, arrhythmia, and pneumonitis.

Permanent discontinuation of ZYNYZ due to an adverse reaction occurred in 11% of patients. These included asthenia, atrial fibrillation, concomitant disease progression of chronic lymphocytic leukemia, demyelinating polyneuropathy, eosinophilic fasciitis, increased transaminases, infusion-related reaction, lung disorder, pancreatitis, polyarthritis, and radiculopathy (1 patient each).

Dosage interruptions due to an adverse reaction occurred in 25% of patients. Adverse reactions or laboratory abnormalities that required dosage interruption in ≥ 2% of patients were increased transaminases, increased lipase, increased amylase, pneumonitis, and pyrexia.

The most common (≥ 10%) adverse reactions were fatigue, musculoskeletal pain, pruritus, diarrhea, rash, pyrexia, and nausea.

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Incyte Corporation at 1-855-463-3463.

Please see the Full Prescribing Information.