NIKTIMVO

1 INDICATIONS AND USAGE NIKTIMVO is indicated for the treatment of chronic graft-versus-host disease (cGVHD) after failure of at least two prior lines of systemic therapy in adult and pediatric patients weighing at least 40 kg. NIKTIMVO is a colony stimulating factor-1 receptor (CSF-1R)-blocking antibody indicated for the treatment of chronic graft-versus-host disease (cGVHD) after failure of at least two prior lines of systemic therapy in adult and pediatric patients weighing at least 40 kg. ( 1 )

2 DOSAGE AND ADMINISTRATION Administer only as an intravenous infusion over 30 minutes. ( 2.3 ) The recommended dosage of NIKTIMVO is 0.3 mg/kg (maximum 35 mg) every 2 weeks in adult and pediatric patients weighing 40 kg and above. ( 2.1 ) See Full Prescribing Information for dosage modifications for adverse reactions ( 2.2 ) and preparation and administration instructions. ( 2.3 ) 2.1 Recommended Dosage For patients weighing at least 40 kg, administer NIKTIMVO 0.3 mg/kg, up to a maximum dose of 35 mg, as an intravenous infusion over 30 minutes every 2 weeks until progression or unacceptable toxicity. 2.2 Dosage Modifications for Adverse Reactions Monitor aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), creatine phosphokinase (CPK), amylase, and lipase prior to the start of NIKTIMVO therapy, every 2 weeks for the first month, and every 1 to 2 months thereafter until abnormalities are resolved. For recommended NIKTIMVO dosage modifications due to adverse reactions, see Table 1. Table 1: Recommended NIKTIMVO Dosage Modifications for Adverse Reactions AST = aspartate aminotransferase; ALT = alanine aminotransferase; ULN = upper limit of normal; ALP = alkaline phosphatase; CPK = creatine phosphokinase. Adverse Reaction Severity Graded per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5. Dosage Modification Infusion-related reactions [see Warnings and Precautions ( 5.1 )] Grade 1 or 2 Temporarily interrupt the infusion until resolution or decrease infusion rate by 50%. Initiate symptomatic treatment (e.g., antihistamines and antipyretics). For subsequent infusions, premedicate and resume the infusion at 50% of the prior infusion rate. Grade 3 or 4 Permanently discontinue NIKTIMVO. Elevation of AST or ALT (on the day of dosing) [see Adverse Reactions ( 6.1 )] Grade 3 with total bilirubin ≤ Grade 1 Withhold NIKTIMVO until recovery to Grade 2, then resume NIKTIMVO at 0.2 mg/kg (maximum 23 mg) every 2 weeks. Elevation of AST or ALT (regardless of the time of the reaction) [see Adverse Reactions ( 6.1 )] ALT or AST ≥ 3 times ULN with total bilirubin ≥ 2 times ULN and ALP < 2 times ULN Withhold NIKTIMVO and investigate for drug-induced liver injury. If confirmed, permanently discontinue NIKTIMVO. Grade 4 Permanently discontinue NIKTIMVO. Elevation of CPK, amylase, or lipase [see Adverse Reactions ( 6.1 )] ≥ Grade 3 If diagnostic evaluation results show no evidence of end-organ damage, continue NIKTIMVO without dose reduction. If diagnostic evaluation results show evidence of end-organ damage, permanently discontinue NIKTIMVO. Symptomatic ≥ Grade 3 Permanently discontinue NIKTIMVO. Other Nonhematologic Adverse Reactions [see Adverse Reactions ( 6.1 )] Grade 3 Withhold NIKTIMVO until recovery to Grade 2: If delayed by ≤ 4 weeks from the planned infusion, resume NIKTIMVO at 0.2 mg/kg (maximum 23 mg) every 2 weeks. If delayed by > 4 weeks from the planned infusion, permanently discontinue NIKTIMVO. Grade 4 Permanently discontinue NIKTIMVO. 2.3 Preparation and Administration Preparation Use aseptic technique to prepare NIKTIMVO. Visually inspect the vial for particulate matter and discoloration prior to dilution. NIKTIMVO is a slightly opalescent, pale brownish yellow solution. Discard the vial if the solution is cloudy, discolored, or contains visible particles. Do not shake the vial. Determine the dose [see Dosage and Administration ( 2.1 )] and total volume of NIKTIMVO solution needed. Each mL of NIKTIMVO contains 50 mg of axatilimab-csfr. Dilution Withdraw the calculated volume of NIKTIMVO solution from the vial and add it into an intravenous infusion bag made of polyvinyl chloride (PVC), polyolefin, polyolefin with polyamide, or ethylene vinyl acetate (EVA) containing 0.9% Sodium Chloride Injection to achieve a final concentration between the range of 0.24 mg/mL and 0.75 mg/mL. Discard vial with any unused portion. Mix diluted solution by gentle invers…

5 WARNINGS AND PRECAUTIONS Infusion-Related Reactions: Interrupt or slow the rate of infusion or permanently discontinue NIKTIMVO based on severity of reaction. ( 2.2 , 5.1 ) Embryo-Fetal Toxicity: May cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception. ( 5.2 , 8.1 , 8.3 ) 5.1 Infusion-Related Reactions NIKTIMVO can cause infusion-related reactions. Infusion-related reactions, including hypersensitivity reactions, occurred in 18% of patients who received NIKTIMVO in the clinical trial (AGAVE-201), with Grade 3 or 4 reactions in 1.3% [see Adverse Reactions ( 6.1 )] . Premedicate with an antihistamine and an antipyretic for patients who have previously experienced an infusion-related reaction to NIKTIMVO [see Dosage and Administration ( 2.2 )] . Monitor patients for signs and symptoms of infusion-related reactions, including fever, chills, rash, flushing, dyspnea, and hypertension. Interrupt or slow the rate of infusion or permanently discontinue NIKTIMVO based on severity of the reaction [see Dosage and Administration ( 2.2 )] . 5.2 Embryo-Fetal Toxicity Based on its mechanism of action, NIKTIMVO may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with NIKTIMVO and for 30 days after the last dose [see Use in Specific Populations ( 8.1 , 8.3 )] .

4 CONTRAINDICATIONS None. None. ( 4 )

8.1 Pregnancy Risk Summary Based on its mechanism of action, NIKTIMVO may cause fetal harm when administered to pregnant women [see Clinical Pharmacology ( 12.1 )] . There are no available data on the use of NIKTIMVO in pregnant women to evaluate for a drug-associated risk. No animal reproductive and developmental toxicity studies have been conducted with axatilimab-csfr. Targeted mutation of CSF-1R or CSF-1 in rodent models results in prenatal and perinatal death, deficits in growth, and pleiotropic impact on multiple organ systems, including skeletal and reproductive. Regulation by CSF-1R on non-mononuclear phagocytic cells and macrophages plays a role in the innate immune protection of the fetus and in pregnancy maintenance and embryo-fetal development. Human immunoglobulin G (IgG) is known to cross the placenta; therefore, NIKTIMVO has the potential to be transmitted from the mother to the developing fetus. Advise women of the potential risk to the fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

6 ADVERSE REACTIONS The following adverse reactions are described elsewhere in the labeling. Infusion-Related Reactions [see Warnings and Precautions ( 5.1 )] The most common (≥ 15%) adverse reactions, including laboratory abnormalities, are increased AST, infection (pathogen unspecified), increased ALT, decreased phosphate, decreased hemoglobin, viral infection, increased GGT, musculoskeletal pain, increased lipase, fatigue, increased amylase, increased calcium, increased CPK, increased ALP, nausea, headache, diarrhea, cough, bacterial infection, pyrexia, and dyspnea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Incyte Corporation at 1-855-463-3463 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Chronic Graft-Versus-Host Disease The safety of NIKTIMVO was evaluated in 79 adult and pediatric patients with cGVHD treated with NIKTIMVO 0.3 mg/kg intravenously every 2 weeks in the AGAVE‑201 trial [see Clinical Studies ( 14 )] . The median duration of treatment was 10.3 months (range: 0.5 to 28.6 months), and 73.4% were treated for more than 6 months. Serious adverse reactions occurred in 44% of patients who received NIKTIMVO. Serious adverse reactions in more than 2 patients included infection (pathogen unspecified), viral infection, and respiratory failure. Permanent discontinuation of NIKTIMVO due to an adverse reaction occurred in 10% of patients and dose reduction due to adverse reaction occurred in 8% of patients. Dose interruptions due to an adverse reaction occurred in 44% of patients. The adverse reactions leading to dose interruption in more than 2 patients were viral infection, infection (pathogen unspecified), bacterial infection, musculoskeletal pain, and pyrexia. The most common (≥ 15%) adverse reactions, including laboratory abnormalities, were increased AST, infection (pathogen unspecified), increased ALT, decreased phosphate, decreased hemoglobin, viral infection, increased gamma glutamyl transferase (GGT), musculoskeletal pain, increased lipase, fatigue, increased amylase, increased calcium, increased CPK, increased ALP, nausea, headache, diarrhea, cough, bacterial infection, pyrexia, and dyspnea. Table 2 summarizes the nonlaboratory adverse reactions in AGAVE-201. Table 2: Adverse Reactions in ≥ 10% of Patients With cGVHD Who Received NIKTIMVO in AGAVE-201 Graded according to NCI CTCAE v5.0. Adverse Reaction NIKTIMVO 0.3 mg/kg intravenously every 2 weeks (N = 79) All Grades (%) Grades 3-4 (%) Infections and infestations Infection (pathogen unspecified) Includes abscess jaw, atypical pneumonia, bacteremia, bronchitis, conjunctivitis, cystitis, device-related infection, enterocolitis infectious, gastroenteritis, gastrointestinal infection, groin abscess, hordeolum, liver abscess, nasopharyngitis, otitis media, otitis media acute, pneumonia, respiratory tract infection, rhinitis, sepsis, sinusitis, tooth infection, upper respiratory tract infection, urinary tract infection, and wound infection. 57 14 Viral infection Includes adenoviral upper respiratory infection, BK virus infection, COVID-19, coronavirus infection, enterovirus infection, gastroenteritis astroviral, gastroenteritis viral, herpes simplex, herpes zoster, influenza, metapneumovirus bronchiolitis, metapneumovirus infection, norovirus infection, oral viral infection, parainfluenza viral bronchitis, parainfluenza virus infection, respiratory syncytial virus infection, rhinovirus infection, viral infection, and viral upper respiratory tract infection. 43 15 Bacterial infection Includes bacterial diarrhea, bacterial vaginosis, campylobacter gastroenteritis, campylobacter infection, cellulitis, clostridium difficile colitis, clostridium difficile infection,…