Permanent J-Code for ZYNYZ™ (retifanlimab-dlwr): Available October 1st, 2023

Effective for claims on or after October 1, 2023:

J9345

Injection, retifanlimab-dlwr, 1 mg

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

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. 

PRODUCT SPECIFICATIONS:

HCPCS Code

J9345

HCPCS Code Descriptor

Injection, retifanlimab-dlwr, 1 mg

NDC Number

10-digit: 50881-006-03

11-digit: 50881-0006-03

WAC Pricing Per Unit

$712 per unit

WAC Pricing Per Package

$14,240 per package

For billing and coding or reimbursement questions, or to request support from a Field Access Manager,

Call 1-855-452-5234, Monday – Friday 8 AM to 8 PM ET 

Visit the ZYNYZ HCP website

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.

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 full Prescribing Information for ZYNYZ for additional Important Safety Information.

ZYNYZ and the ZYNYZ logo are trademarks of Incyte.

Incyte and the Incyte logo are registered trademarks of Incyte. 

All other trademarks are the property of their respective owners. 

© 2023, Incyte. MAT-RET-00166 09/23