FDA label b6b9ef2d-53cd-47c7-9ee5-c0610635d35b

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 )] .

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, enterococcal infection, erysipelas, hemophilus infection, lower respiratory tract infection bacterial, pseudomonal skin infection, staphylococcal bacteremia, staphylococcal infection, stenotrophomonas infection, streptococcal infection, and urinary tract infection enterococcal. 15 8 Musculoskeletal and connective tissue disorders Musculoskeletal pain Includes arthralgia, back pain, flank pain, musculoskeletal pain, myalgia, pain in extremity. 35 3 General disorders and administration site conditions Fatigue Includes asthenia, fatigue, and malaise. 32 4 Pyrexia 15 1 Edema Includes localized edema and peripheral edema. 13 1 Gastrointestinal disorders Nausea Includes nausea and vomiting. 23 3 Diarrhea Includes colitis and diarrhea. 18 5 Nervous system disorders Headache Includes headache and migraine. 20 1 Dizziness Includes dizziness and dizziness postural. 11 0 Respiratory, thoracic and mediastinal disorders Cough Includes cough and productive cough. 18 0 Dyspnea Includes dyspnea and dyspnea exertional. 15 3 Immune system disorders Drug hypersensitivity Includes bronchospasm, flushing, hot flush, hypersensitivity, infusion-related hypersensitivity reaction, infusion-related reaction, and urticaria. 13 3 Metabolism and nutrition disorders Decreased appetite 11 4 Vascular disorders Hemorrhage Includes contusion, epistaxis, hematochezia, hematoma, and vaginal hemorrhage. 11 1 Skin and subcutaneous tissue disorders Rash Includes dermatitis bullous, dermatitis exfoliative generalized, rash, and rash maculo-papular. 10 0 Clinically relevant adverse reactions in < 10% of patients who received NIKTIMVO included: Eye disorders : periorbital edema Skin and subcutaneous skin disorders : pruritus Vascular disorders : hypertension Table 3 summarizes the laboratory abnormalities in AGAVE-201. Table 3: Selected Laboratory Abnormalities in Patients with cGVHD Who Received NIKTIMVO in AGAVE-201 NA = not applicable. Laboratory Abnormality NIKTIMVO 0.3 mg/kg intravenously every 2 weeks (N=79) All Grades The denominator used to calculate the rate varied from 78 to 79 based on the number of patients with at least 1 post-treatment value. (%) Grade 3 or 4 (%) Hematology Decreased hemoglobin 48 4 Chemistry Increased aspartate aminotransferase 61 5 Increased alanine aminotransferase 51 3 Decreased phosphate 51 NA Increased gamma glutamyl transferase 39 4 Increased lipase 34 3 Increased amylase 32 0 Increased calcium 31 1 Increased alkaline phosphatase 28 0 Increased creatine phosphokinase 25 0 Immunogenicity: Anti-Drug Antibody–Associated Adverse Reactions In 276 patients with cGVHD who received NIKTIMVO in clinical trials, among the patients who developed anti-drug antibodies (ADAs), hypersensitivity reactions occurred in 26% (13/50) of patients with neutralizing antibodies (NAb) and in 4% (2/45) of those without NAb [see Clinical Pharmacology ( 12.6 )] .

<table width="748.76px"><caption>Table 2: Adverse Reactions in &#x2265; 10% of Patients With cGVHD Who Received NIKTIMVO in AGAVE-201</caption><col/><col/><col/><tfoot><tr><td valign="top" colspan="3" styleCode=" Toprule">Graded according to NCI CTCAE v5.0.</td></tr></tfoot><tbody><tr><td rowspan="2" styleCode=" Botrule Toprule Lrule Rrule"><content styleCode="bold">Adverse Reaction </content></td><td align="center" colspan="2" styleCode=" Botrule Toprule Lrule Rrule"><content styleCode="bold">NIKTIMVO 0.3 mg/kg intravenously every 2 weeks (N = 79) </content></td></tr><tr><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><content styleCode="bold">All Grades (%) </content></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><content styleCode="bold">Grades 3-4 (%) </content></td></tr><tr><td colspan="3" styleCode=" Botrule Toprule Lrule Rrule"><content styleCode="bold">Infections and infestations</content> </td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule">Infection (pathogen unspecified)<footnote ID="FOOT_24380">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.</footnote></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">57</td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">14</td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule">Viral infection<footnote ID="FOOT_24381">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.</footnote> </td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">43</td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">15</td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule">Bacterial infection<footnote ID="FOOT_24382">Includes bacterial diarrhea, bacterial vaginosis, campylobacter gastroenteritis, campylobacter infection, cellulitis, clostridium difficile colitis, clostridium difficile infection, enterococcal infection, erysipelas, hemophilus infection, lower respiratory tract infection bacterial, pseudomonal skin infection, staphylococcal bacteremia, staphylococcal infection, stenotrophomonas infection, streptococcal infection, and urinary tract infection enterococcal.</footnote> </td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">15</td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">8</td></tr><tr><td colspan="3" styleCode=" Botrule Toprule Lrule Rrule"><content styleCode="bold">Musculoskeletal and connective tissue disorders</content> </td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule">Musculoskeletal pain<footnote ID="FOOT_24383">Includes arthralgia, back pain, flank pain, musculoskeletal pain, myalgia, pain in extremity.</footnote> </td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">35</td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">3</td></tr><tr><td colspan="3" styleCode=" Botrule Toprule Lrule Rrule"><content styleCode="bold">General disorders and administration site conditions</content> </td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule">Fatigue<footnote ID="FOOT_24384">Includes asthenia, fatigue, and malaise.</footnote> </td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">32</td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">4</td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule">Pyrexia </td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">15</td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">1</td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule">Edema<footnote ID="FOOT_24385">Includes localized edema and peripheral edema.</footnote> </td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">13</td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">1</td></tr><tr><td colspan="3" styleCode=" Botrule Toprule Lrule Rrule"><content styleCode="bold">Gastrointestinal disorders</content></td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule">Nausea<footnote ID="FOOT_24386">Includes nausea and vomiting.</footnote> </td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">23</td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">3</td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule">Diarrhea<footnote ID="FOOT_24387">Includes colitis and diarrhea.</footnote> </td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">18</td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">5</td></tr><tr><td colspan="3" styleCode=" Botrule Toprule Lrule Rrule"><content styleCode="bold">Nervous system disorders</content> </td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule">Headache<footnote ID="FOOT_24388">Includes headache and migraine.</footnote> </td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">20</td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">1</td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule">Dizziness<footnote ID="FOOT_24389">Includes dizziness and dizziness postural.</footnote> </td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">11</td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">0</td></tr><tr><td colspan="3" styleCode=" Botrule Toprule Lrule Rrule"><content styleCode="bold">Respiratory, thoracic and mediastinal disorders</content></td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule">Cough<footnote ID="FOOT_24390">Includes cough and productive cough.</footnote> </td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">18</td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">0</td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule">Dyspnea<footnote ID="FOOT_24391">Includes dyspnea and dyspnea exertional.</footnote> </td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">15</td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">3</td></tr><tr><td colspan="3" styleCode=" Botrule Toprule Lrule Rrule"><content styleCode="bold">Immune system disorders</content> </td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule">Drug hypersensitivity<footnote ID="FOOT_24392">Includes bronchospasm, flushing, hot flush, hypersensitivity, infusion-related hypersensitivity reaction, infusion-related reaction, and urticaria.</footnote> </td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">13</td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">3</td></tr><tr><td colspan="3" styleCode=" Botrule Toprule Lrule Rrule"><content styleCode="bold">Metabolism and nutrition disorders</content> </td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule">Decreased appetite </td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">11</td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">4</td></tr><tr><td colspan="3" styleCode=" Botrule Toprule Lrule Rrule"><content styleCode="bold">Vascular disorders</content> </td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule">Hemorrhage<footnote ID="FOOT_24393">Includes contusion, epistaxis, hematochezia, hematoma, and vaginal hemorrhage.</footnote> </td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">11</td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">1</td></tr><tr><td colspan="3" styleCode=" Botrule Toprule Lrule Rrule"><content styleCode="bold">Skin and subcutaneous tissue disorders</content> </td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule">Rash<footnote ID="FOOT_24394">Includes dermatitis bullous, dermatitis exfoliative generalized, rash, and rash maculo-papular.</footnote> </td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">10</td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">0</td></tr></tbody></table>

<table width="635.4px"><caption>Table 3: Selected Laboratory Abnormalities in Patients with cGVHD Who Received NIKTIMVO in AGAVE-201</caption><col/><col/><col/><tfoot><tr><td colspan="3" styleCode=" Toprule">NA = not applicable.</td></tr></tfoot><tbody><tr><td rowspan="2" styleCode=" Botrule Toprule Lrule Rrule"><content styleCode="bold">Laboratory Abnormality</content></td><td align="center" colspan="2" styleCode=" Botrule Toprule Lrule Rrule"><content styleCode="bold">NIKTIMVO 0.3 mg/kg intravenously every 2 weeks (N=79)</content></td></tr><tr><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><content styleCode="bold">All Grades<footnote ID="FOOT_24410">The denominator used to calculate the rate varied from 78 to 79 based on the number of patients with at least 1 post-treatment value.</footnote> (%)</content> </td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><content styleCode="bold">Grade 3 or 4<footnoteRef IDREF="FOOT_24410"/> (%)</content></td></tr><tr><td colspan="3" styleCode=" Botrule Toprule Lrule Rrule"><content styleCode="bold">Hematology</content></td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule">Decreased hemoglobin </td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">48</td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">4</td></tr><tr><td colspan="3" styleCode=" Botrule Toprule Lrule Rrule"><content styleCode="bold">Chemistry</content></td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule">Increased aspartate aminotransferase </td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">61</td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">5</td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule">Increased alanine aminotransferase </td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">51</td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">3</td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule">Decreased phosphate </td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">51</td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">NA</td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule">Increased gamma glutamyl transferase </td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">39</td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">4</td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule">Increased lipase </td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">34</td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">3</td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule">Increased amylase </td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">32</td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">0</td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule">Increased calcium </td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">31</td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">1</td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule">Increased alkaline phosphatase </td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">28</td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">0</td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule">Increased creatine phosphokinase </td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">25</td><td align="center" styleCode=" Botrule Toprule Lrule Rrule">0</td></tr></tbody></table>