b'ADSTILADRIN (nadofaragene firadenovec-vncg) suspension, forClinically relevant adverse reactions in 10% of patients who received intravesical use ADSTILADRIN included coronary artery disease (1.3%), acute coronary syndrome (1.3%), atrial fibrillation (1.3%), dehydration (1.3%), hypoglycemia Brief Summary of FULL PRESCRIBING INFORMATION (low blood sugar) (1.3%), syncope (fainting) (1.3%), heart failure (0.6%), 1 INDICATIONS AND USAGE pericarditis, (0.6%), brain edema (swelling) (0.6%), bile duct stone (0.6%), and ADSTILADRIN is indicated for the treatment of adult patients with high-risksepsis (0.6%). Table 2 summarizes the laboratory abnormalities in CS-003.Bacillus Calmette-Gurin (BCG)-unresponsive non-muscle invasive bladderTable 2: Selected Laboratory Abnormalities (15.0%) That Worsened from cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors. Baseline in Patients with NMIBC in CS-0034CONTRAINDICATIONS Laboratory Abnormality ADSTILADRIN 1 ADSTILADRIN 1ADSTILADRIN is contraindicated in patients with prior hypersensitivity reactionsAll Grades (%) Grade 3 or 4 (%)to interferon alfa or to any component of the product [see Description]. Chemistry5WARNINGS AND PRECAUTIONS5.1Risk of Muscle Invasive or Metastatic Bladder Cancer with DelayedGlucose increased 38 6Cystectomy Triglycerides increased 30 1.9Delaying cystectomy in patients with BCG-unresponsive CIS could lead todevelopment of muscle invasive or metastatic bladder cancer, which can beCreatinine increased 17 0lethal. The risk of developing muscle-invasive or metastatic bladder cancer increases the longer cystectomy is delayed in the presence of persisting CIS. Phosphate decreased 16 1.4Of the patients with CIS treated with ADSTILADRIN on Study CS-003 whoHematologyunderwent subsequent radical cystectomy and for whom pathologic data were available, 14% (n = 6) had muscle-invasive (T2 or greater) disease at cystectomy.Hemoglobin decreased 16 0.6Median time from persistence or recurrence of CIS to cystectomy in these patients was 235 days (range 38 to 582 days). Two additional patients who did not 1 The denominator used to calculate the rate varied from 148 to 156 based on undergo cystectomy experienced progression to muscle-invasive disease duringthe number of patients with a baseline value and at least one post-treatment the treatment period. value.If patients with CIS do not have a complete response to treatment after 38USE IN SPECIFIC POPULATIONSmonths or if CIS recurs, consider cystectomy. 8.1Pregnancy5.2Risk of Disseminated Adenovirus Infection Risk SummaryImmunocompromised persons, including those receiving immunosuppressantAdequate and well-controlled studies with ADSTILADRIN have not been therapy, may be at risk for disseminated adenovirus infection because of theconducted in pregnant women. Animal reproductive and developmental possible presence of low levels of replication-competent adenovirus intoxicity studies have not been conducted with ADSTILADRIN. Advise pregnant ADSTILADRIN. Individuals who are immunosuppressed or immune-deficientwomen of the potential risk to a fetus.should not come into contact with ADSTILADRIN. In the U.S. general population, the estimated background risk of major birth 6ADVERSE REACTIONS defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 6.1Clinical Trials Experience to 20%, respectively.Because clinical trials are conducted under widely varying conditions, adverse 8.2Lactationreaction rates observed in the clinical trials of a drug cannot be directlyRisk Summarycompared to rates in the clinical trials of another drug and may not reflect theThere is no information regarding the presence of ADSTILADRIN in human rates observed in practice. milk, the effects on the breastfed infant, or the effects on milk production.The safety of ADSTILADRIN was evaluated in Study CS-003, a multicenter,The developmental and health benefits of breastfeeding should be considered single-arm, open-label study in 157 U.S. patients [see Clinical Studies] withalong with the mothers clinical need for ADSTILADRIN and any potential high-risk BCG-unresponsive NMIBC, 107 of whom had BCG-unresponsiveadverse effects on the breastfed infant from ADSTILADRIN or from the carcinoma in situ (CIS) with or without papillary tumors. underlying maternal condition.Patients received 75 mL (3 x 10 11vp/mL) ADSTILADRIN administered8.3Females and Males of Reproductive Potentialintravesically once every 3 months for up to 12 months [see Clinical Studies].No nonclinical or clinical studies were performed to evaluate the effect of All patients with an absence of high-risk recurrence or progression wereADSTILADRIN on fertility.offered continued treatment every 3 months beyond 12 months. The medianPregnancy Testingnumber of instillations of ADSTILADRIN was 2 (range 1 to 5). Verify pregnancy status in females of reproductive potential prior to initiating Serious adverse reactions occurred in 11% of patients who received ADSTILADRIN.ADSTILADRIN.Serious adverse reactions occurring in 1% of patients included coronary artery disease and hematuria (blood in urine). ContraceptionPermanent discontinuation of ADSTILADRIN due to an adverse reaction occurredFemalesin 3 (1.9%) patients. Adverse reactions that resulted in permanent discontinuationAdvise females of reproductive potential to use effective contraception during of ADSTILADRIN included bladder spasm, instillation site discharge, and benigntreatment with ADSTILADRIN and for 6 months following the last dose.neoplasm of the bladder. MalesDosage interruptions of ADSTILADRIN due to an adverse reaction occurred inAdvise male patients with female partners of reproductive potential to use 54 (34%) patients. Adverse reactions in 10% of patients that required dosageeffective contraception during treatment with ADSTILADRIN and for 3 interruption included instillation site discharge, bladder spasm and months following the last dose.micturition urgency. 8.4Pediatric UseThe most common (10%) adverse reactions, including laboratory abnormalitiesSafety and effectiveness of ADSTILADRIN in pediatric patients have not been (15%), were glucose increased, instillation site discharge, triglycerides increased,established.fatigue, bladder spasm, micturition (urination) urgency, creatinine increased,8.5Geriatric Usehematuria (blood in urine), phosphate decreased, chills, dysuria, and pyrexia (fever). Clinical studies of ADSTILADRIN in BCG-unresponsive high-risk NMIBC with Tables 1 and 2 summarize adverse reactions and laboratory abnormalities,CIS did not include sufficient numbers of patients younger than 65 years of respectively, in patients on ADSTILADRIN in CS-003. age to determine whether safety and effectiveness differ from older patients.Clinically relevant adverse reaction in 10% of patients who received8.6Gender-specific UseADSTILADRIN include syncope (fainting) (1.3%). In clinical studies with ADSTILADRIN, no overall differences in safety or Table 1: Adverse Reactions (10%) in Patients with NMIBC in CS-003 efficacy were observed between females and males.Adverse Reaction ADSTILADRIN n=157*Grades 1 or 2 (%)General disorders and administrationsite conditionsInstillation site discharge 33Fatigue 24Chills 16Pyrexia 15 Manufactured for:Renal and urinary disorders Ferring Pharmaceuticals2770 Kastrup, DenmarkBladder spasm 20 by:FinVector Oy. Micturition urgency 19 Kuopio, FinlandHematuria 17 Please see Full Prescribing Information at adstiladrinHCP.comDysuria 162024 Ferring. ADSTILADRIN, Ferring and the Ferring Pharmaceuticals logo are trademarks of Ferring. *Graded per NCI CTCAE v4.03; there were no Grade 3 or 4 reactions. US-ADST-2400181v208/24'