FDA label d44ffd1f-d257-4d1a-e053-2a95a90a024c

5 WARNINGS AND PRECAUTIONS Ureteric Obstruction: Ureteric obstruction may occur. Monitor patients for signs and symptoms of ureteric obstruction. Transient or long-term ureteral stents or alternative procedures may be required. Withhold or permanently discontinue JELMYTO based on the severity of the ureteric obstruction. ( 5.1 ) Bone Marrow Suppression: Thrombocytopenia and neutropenia may occur. Monitor blood counts. Withhold or permanently discontinue JELMYTO based on the severity. ( 5.2 ) Embryo-Fetal Toxicity: Can cause fetal harm. Advise of potential risk to a fetus and to use effective contraception. ( 5.3 , 8.1 , 8.3 ) 5.1 Ureteric Obstruction Ureteric obstruction, including ureteral stenosis and hydronephrosis, occurred in patients receiving JELMYTO. In the OLYMPUS study, ureteric obstruction was reported in 58% (n=41) of patients receiving JELMYTO, including 17% (n=12) of patients who experienced Grade 3 obstruction. The median time to first onset was 72 days (range: 15-462). Interventions in the 41 patients experiencing ureteric obstruction included ureteral stent placement (88%), balloon dilatation (29%), and nephroureterectomy (4.9%). In the 36 patients who required ureteral stent placement, the median duration of indwelling stents was 52 days (range: 1-292). Ureteric obstruction did not resolve or resolved with sequelae in 44% (n=18) of these patients. Of the 41 patients who experienced ureteric obstruction, 17% (n=7) experienced Grades 1-2 increase in serum creatinine. In the 42 patients who only received JELMYTO during the treatment phase (no maintenance therapy), ureteric obstruction was reported in 40% (n=17). Monitor patients for signs and symptoms of ureteric obstruction, including flank pain, and fever, and for changes in renal function. Patients who experience obstruction may require transient or long-term ureteral stents or alternative procedures. Withhold or permanently discontinue JELMYTO based on the severity of ureteric obstruction. 5.2 Bone Marrow Suppression The use of JELMYTO can result in bone marrow suppression, particularly thrombocytopenia and neutropenia. In the OLYMPUS study, Grade 3 thrombocytopenia occurred in three patients, Grade 3 anemia in one patient, and Grade 3 neutropenia in one patient. Gross extravasation of JELMYTO via urinary tract perforation or impaired mucosa was not observed in these patients. The following tests should be obtained prior to each treatment: Platelet count, white blood cell count differential and hemoglobin. Withhold JELMYTO for Grade 2 thrombocytopenia or neutropenia. Permanently discontinue for Grade 3 or greater thrombocytopenia or neutropenia. 5.3 Embryo-Fetal Toxicity Based on findings in animals and mechanism of action, JELMYTO can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of mitomycin resulted in teratogenicity. Advise females of reproductive potential to use effective contraception during treatment with JELMYTO and for 6 months following the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with JELMYTO and for 3 months following the last dose [see Use in Specific Populations (8.1 , 8.3) and Clinical Pharmacology (12.1) ].

6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling: Ureteric Obstruction [see Warnings and Precautions (5.1) ] Bone Marrow Suppression [see Warnings and Precautions (5.2) ] The most common adverse reactions (≥ 20%) are ureteric obstruction, urinary tract infection, hematuria, flank pain, nausea, dysuria, renal dysfunction, vomiting, fatigue, and abdominal pain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact UroGen Pharma at 1-855-987-6436 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect rates observed in practice. The safety of JELMYTO was evaluated in OLYMPUS, an open-label, single-arm study in 71 patients with LG-UTUC [see Clinical Studies (14) ] . For the 71 patients treated with JELMYTO during the treatment period, the median number of instillations was 6 (range: 3-6). Following initial treatment, 29 patients were treated with up to 11 doses of maintenance instillations, with a median of 6 instillations (range: 0-11). Serious adverse reactions occurred in 39% of patients who received JELMYTO. Serious adverse reactions in > 3% of patients included ureteric obstruction (including ureteric stenosis and hydronephrosis), flank pain, and urosepsis. Two deaths occurred due to cerebrovascular accident and failure to thrive. JELMYTO was permanently discontinued due to an adverse reaction in 17 (24%) patients, including 11 patients who discontinued during the treatment phase and 6 who discontinued during the maintenance phase. Adverse reactions resulting in study drug discontinuation of JELMYTO in > 3% of patients who received JELMYTO included ureteric obstruction. Dosage interruptions due to an adverse reaction occurred in 37% of patients who received JELMYTO. Adverse reactions requiring dosage interruption in > 3% of patients who received JELMYTO included renal dysfunction, ureteric obstruction, urinary tract infection, and flank pain. The most common adverse reactions (≥ 20%) reported were ureteric obstruction, urinary tract infection, hematuria, flank pain, nausea, dysuria, renal dysfunction, vomiting, fatigue, and abdominal pain. Table 1 summarizes the adverse reactions in OLYMPUS. Table 1: Adverse Reactions (≥ 10% All Grades) in Patients Who Received JELMYTO in OLYMPUS JELMYTO Graded per National Cancer Institute Common Terminology Criteria for Adverse Events. Version 5.0 (NCI CTCAE v5) (n=71) Adverse Reaction All Grades (%) Grade 3-4 (%) Renal and urinary disorders Ureteric Obstruction Includes hydronephrosis, obstructive uropathy, pelvi-ureteric obstruction, ureteric obstruction, ureteric stenosis, and urinary tract obstruction. 58 17 Ureteric stenosis 44 9 Hydronephrosis 18 6 Urinary tract obstruction 7 1.4 Pelvi-ureteric obstruction 6 1.4 Ureteric obstruction 2.8 1.4 Obstructive uropathy 1.4 0 Flank pain Includes flank pain and back pain. 41 2.8 Hematuria Includes hematuria and hemorrhage urinary tract. 34 2.8 Urinary tract infection Includes urinary tract infection, pyelonephritis, and urinary tract infection fungal. 34 4.2 Renal dysfunction Includes renal impairment, acute kidney injury, and renal failure. 25 2.8 Dysuria 23 0 Pollakiuria 14 0 Gastrointestinal disorders Nausea 25 1.4 Abdominal pain Includes abdominal pain and abdominal pain lower. 28 1.4 Vomiting 20 4.2 General disorders and administration site conditions Fatigue Includes asthenia and fatigue. 27 1.4 Pyrexia 13 1.4 Chills 11 0 Blood and lymphatic system disorders Anemia 14 1.4 Skin and subcutaneous tissue disorders Pruritus 13 0 Metabolism and nutrition disorders Decreased appetite 10 0 Vascular disorders Hypertension 10 4.2 Selected clinically relevant adverse reactions in < 10% and ≥ 2% of patients who received JELMYTO in OLYMPUS include urinary tract inflammation, bladder spasm, urosepsis, hypersensitivity, and instillation site pain. Table 2 summarizes the laboratory abnormalities in OLYMPUS. Table 2: Select Laboratory Abnormalities (≥ 10%) Worsening from Baseline in Patients Who Received JELMYTO in OLYMPUS Laboratory Abnormality Graded per National Cancer Institute Common Terminology Criteria for Adverse Events. Version 5.0 (NCI CTCAE v5). Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement available. JELMYTO All Grades (%) Grade ≥ 3 (%) Hematology Anemia 38 0 Lymphopenia 21 2.9 Thrombocytopenia 21 2.8 Chemistry Estimated Glomerular Filtration Rate (eGFR) eGFR calculated per MDRD (Modification of Diet in Renal Disease) equation 38 11 Creatinine increased 34 0 Hypoalbuminemia 28 2.8 Hypocalcemia 16 0 Hyperuricemia 16 16 Hyperkalemia 13 1.4 Hypernatremia 11 0

<table width="80%"><caption>Table 1: Adverse Reactions (&#x2265; 10% All Grades) in Patients Who Received JELMYTO in OLYMPUS</caption><col width="60%" align="left" valign="middle"/><col width="20%" align="center" valign="middle"/><col width="20%" align="center" valign="middle"/><thead><tr><th styleCode="Lrule Rrule"/><th align="center" colspan="2" styleCode="Rrule Botrule">JELMYTO <footnote ID="K804">Graded per National Cancer Institute Common Terminology Criteria for Adverse Events. Version 5.0 (NCI CTCAE v5)</footnote> (n=71) </th></tr><tr><th align="center" styleCode="Lrule Rrule">Adverse Reaction</th><th styleCode="Rrule">All Grades (%) </th><th styleCode="Rrule">Grade 3-4 (%) </th></tr></thead><tbody><tr styleCode="Botrule"><td colspan="3" align="left" styleCode="Lrule Rrule"><content styleCode="bold">Renal and urinary disorders</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Ureteric Obstruction <footnote ID="K838">Includes hydronephrosis, obstructive uropathy, pelvi-ureteric obstruction, ureteric obstruction, ureteric stenosis, and urinary tract obstruction.</footnote></td><td styleCode="Rrule">58</td><td styleCode="Rrule">17</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Ureteric stenosis</td><td styleCode="Rrule">44</td><td styleCode="Rrule">9</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hydronephrosis</td><td styleCode="Rrule">18</td><td styleCode="Rrule">6</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Urinary tract obstruction</td><td styleCode="Rrule">7</td><td styleCode="Rrule">1.4</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Pelvi-ureteric obstruction</td><td styleCode="Rrule">6</td><td styleCode="Rrule">1.4</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Ureteric obstruction</td><td styleCode="Rrule">2.8</td><td styleCode="Rrule">1.4</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Obstructive uropathy</td><td styleCode="Rrule">1.4</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Flank pain <footnote ID="K917">Includes flank pain and back pain.</footnote></td><td styleCode="Rrule">41</td><td styleCode="Rrule">2.8</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hematuria <footnote ID="K930">Includes hematuria and hemorrhage urinary tract.</footnote></td><td styleCode="Rrule">34</td><td styleCode="Rrule">2.8</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Urinary tract infection <footnote ID="K943">Includes urinary tract infection, pyelonephritis, and urinary tract infection fungal.</footnote></td><td styleCode="Rrule">34</td><td styleCode="Rrule">4.2</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Renal dysfunction <footnote ID="K956">Includes renal impairment, acute kidney injury, and renal failure.</footnote></td><td styleCode="Rrule">25</td><td styleCode="Rrule">2.8</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Dysuria</td><td styleCode="Rrule">23</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Pollakiuria</td><td styleCode="Rrule">14</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td colspan="3" align="left" styleCode="Lrule Rrule"><content styleCode="bold">Gastrointestinal disorders</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Nausea</td><td styleCode="Rrule">25</td><td styleCode="Rrule">1.4</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Abdominal pain <footnote ID="K1011">Includes abdominal pain and abdominal pain lower.</footnote></td><td styleCode="Rrule">28</td><td styleCode="Rrule">1.4</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Vomiting</td><td styleCode="Rrule">20</td><td styleCode="Rrule">4.2</td></tr><tr styleCode="Botrule"><td colspan="3" align="left" styleCode="Lrule Rrule"><content styleCode="bold">General disorders and administration site conditions</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Fatigue <footnote ID="K1044">Includes asthenia and fatigue.</footnote></td><td styleCode="Rrule">27</td><td styleCode="Rrule">1.4</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Pyrexia</td><td styleCode="Rrule">13</td><td styleCode="Rrule">1.4</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Chills</td><td styleCode="Rrule">11</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td colspan="3" align="left" styleCode="Lrule Rrule"><content styleCode="bold">Blood and lymphatic system disorders</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Anemia</td><td styleCode="Rrule">14</td><td styleCode="Rrule">1.4</td></tr><tr styleCode="Botrule"><td colspan="3" align="left" styleCode="Lrule Rrule"><content styleCode="bold">Skin and subcutaneous tissue disorders</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Pruritus</td><td styleCode="Rrule">13</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td colspan="3" align="left" styleCode="Lrule Rrule"><content styleCode="bold">Metabolism and nutrition disorders</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Decreased appetite</td><td styleCode="Rrule">10</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td colspan="3" align="left" styleCode="Lrule Rrule"><content styleCode="bold">Vascular disorders</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hypertension</td><td styleCode="Rrule">10</td><td styleCode="Rrule">4.2</td></tr></tbody></table>

<table width="80%"><caption>Table 2: Select Laboratory Abnormalities (&#x2265; 10%) Worsening from Baseline in Patients Who Received JELMYTO in OLYMPUS</caption><col width="50%" align="left" valign="middle"/><col width="20%" align="center" valign="middle"/><col width="30%" align="center" valign="middle"/><thead><tr><th rowspan="2" styleCode="Lrule Rrule">Laboratory Abnormality <footnote ID="K1180">Graded per National Cancer Institute Common Terminology Criteria for Adverse Events. Version 5.0 (NCI CTCAE v5). Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement available.</footnote></th><th colspan="2" styleCode="Rrule Botrule">JELMYTO</th></tr><tr><th align="center" styleCode="Rrule">All Grades (%)</th><th styleCode="Rrule">Grade &#x2265; 3 (%)</th></tr></thead><tbody><tr styleCode="Botrule"><td colspan="3" styleCode="Lrule Rrule"><content styleCode="bold">Hematology</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Anemia</td><td styleCode="Rrule">38</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Lymphopenia</td><td styleCode="Rrule">21</td><td styleCode="Rrule">2.9</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Thrombocytopenia</td><td styleCode="Rrule">21</td><td styleCode="Rrule">2.8</td></tr><tr styleCode="Botrule"><td colspan="3" styleCode="Lrule Rrule"><content styleCode="bold">Chemistry</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Estimated Glomerular Filtration Rate (eGFR) <footnote ID="K1249">eGFR calculated per MDRD (Modification of Diet in Renal Disease) equation</footnote></td><td styleCode="Rrule">38</td><td styleCode="Rrule">11</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Creatinine increased</td><td styleCode="Rrule">34</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hypoalbuminemia</td><td styleCode="Rrule">28</td><td styleCode="Rrule">2.8</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hypocalcemia</td><td styleCode="Rrule">16</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hyperuricemia</td><td styleCode="Rrule">16</td><td styleCode="Rrule">16</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hyperkalemia </td><td styleCode="Rrule">13</td><td styleCode="Rrule">1.4</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hypernatremia</td><td styleCode="Rrule">11</td><td styleCode="Rrule">0</td></tr></tbody></table>