Adstiladrin

Nadofaragene firadenovec-vncg · Suspension · Intravesical

Prescription (Rx)

Uses

1 INDICATIONS AND USAGE ADSTILADRIN ® is indicated for the treatment of adult patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-Muscle Invasive Bladder Cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors. ADSTILADRIN is a non-replicating adenoviral vector-based gene therapy indicated for the treatment of adult patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors. ( 1 )

Dosage and administration

Important Administration Instructions ADSTILADRIN is for intravesical instillation only. ADSTILADRIN is not for intravenous use, topical use, or oral administration. Premedication with an anticholinergic is recommended before each instillation of ADSTILADRIN. ( 2.1 ) Administer ADSTILADRIN by intravesical instillation only. ( 2.1 ) ADSTILADRIN is not for intravenous use, topical use, or oral administration. ( 2 ) The dose is 75 mL of ADSTILADRIN at a concentration of 3 x 10 11 viral particles (vp)/mL, instilled once every three (3) months. ( 2.1 ) Allow ADSTILADRIN to be left in the bladder for 1 hour following instillation. ( 2.3 ) 2.1 Dose The recommended dose of ADSTILADRIN is 75 mL at a concentration of 3 x 10 11 viral particles (vp)/mL instilled once every three (3) months into the bladder via a urinary catheter [ see Dosage and Administration (2.2) ]. Premedication with an anticholinergic is recommended before each instillation of ADSTILADRIN. 2.2 Preparation and Handling ADSTILADRIN is a non-replicating adenoviral vector-based gene therapy. Follow universal biosafety precautions for handling. Individuals who are immunosuppressed or immune-deficient, should not prepare, administer, or come into contact with ADSTILADRIN [ see Warnings and Precautions ( 5 ) ]. ADSTILADRIN is provided as a sterile frozen suspension. All four vials of ADSTILADRIN must be thawed and brought to room temperature (20°C to 25°C [68°F to 77°F]) prior to use. Do not expose the vials to higher temperatures (>25°C [77°F]). Protect from light. DO NOT refreeze. ADSTILADRIN may be moved between refrigerator and room temperature if the total storage time at each condition is not exceeded (24 hours at room temperature and 7 days refrigerated including thawing time). [ see How Supplied/Storage and Handling (16) ] WHEN THAWING IN WATER BATH Frozen ADSTILADRIN vials will thaw in approximately 25 minutes outside the cardboard nest when placed directly in a water bath maintained at 25°C [77ºF]. Place the vials in the water bath, ensuring that the water level is sufficient to cover the product within the vials. Following thawing, remove vials from the water bath and dry with a clean paper towel to remove any residual moisture prior to further handling. WHEN THAWING AT ROOM TEMPERATURE Frozen ADSTILADRIN vials will thaw in approximately 3 to 5 hours outside the cardboard nest when placed at room temperature (up to 25°C [77ºF]) (8 to 10 hours inside the nest). WHEN THAWING IN REFRIGERATOR Frozen ADSTILADRIN vials will thaw in approximately 4 to 5 hours outside the cardboard nest when placed in the refrigerator (up to 8°C [46ºF]) (11 to 13 hours inside the nest). Subsequent time for bringing thawed ADSTILADRIN to room temperature is approximately 2 hours 30 minutes outside of the cardboard nest (6 hours inside the nest). Inspection and Preparing ADSTILADRIN for instillation Visually inspect all 4 vials for visible particles and discoloration. The suspension is clear to slightly opalescent and may contain opalescent flecks. Do not use if visible particles or discoloration are observed. Mix gently. Do not shake. Items required for instillation: 70% isopropyl ethanol pads Four (4) thawed vials of ADSTILADRIN Four (4) vented vial adapters suitable for a standard 20 mL vial Two (2) standard 50 or 60 mL polypropylene Luer lock syringes or one (1) Luer lock syringe equal to or greater than 75 mL (max 100 mL) Two (2) Luer lock adapters One (1) straight, or intermittent, urethral catheter with a proximal funnel opening that will accommodate the Luer lock adapter. Use only catheters made of vinyl/PVC (uncoated or coated with hydrogel), red rubber latex or silicone to instill ADSTILADRIN. Do not use catheters coated or embedded with silver or antibiotics. Using aseptic technique, remove the cap from an ADSTILADRIN vial. Prior to vial access, wipe the access diaphragm with 70% isopropyl alcohol pad, allowing it to air dry before proceeding. Attach a vented vial adapter according to manufacturer’s instructions. Connect the syringe to the vial adapter and withdraw the contents of the vial into the syringe. Repeat steps 1-2 for the remaining three (3) vials until 75 mL has been withdrawn into one (1) or two (2) syringes. The volumes in the syringes do not have to be equal. Discard any remaining volume according to universal precautions. If unable to administer the suspension shortly after withdrawal, the solution may be stored in syringes for up to 6 hours at room temperature (20°C to 25°C [68°F to 77°F]) protected from light. Treat any ADSTILADRIN spills or unused portion with a virucidal agent (such as sodium hypochlorite with 0.5% active chlorine or 6% hydrogen peroxide solution) for 15 minutes. Disposable materials that have come into contact with ADSTILADRIN should be placed in biohazard containers for destruction. Non-disposable equipment may be decontaminated according to the facility’s standard operating procedures. [ see Patient Counseling Information ( 17 ) ]. Inspection and Preparing ADSTILADRIN for instillation Visually inspect all 4 vials for visible particles and discoloration. The suspension is clear to slightly opalescent and may contain opalescent flecks. Do not use if visible particles or discoloration are observed. Mix gently. Do not shake. Items required for instillation:
• Four (4) thawed vials of ADSTILADRIN
• Four (4) vented vial adapters suitable for a standard 20 mLvial
• Two (2) standard 50 or 60 mL polypropylene Luer lock syringes or one (1) Luer lock syringe equal to or greater than 75 mL (max 100 mL)
• Two (2) Luer lock adapters - One (1) straight, or intermittent, urethral catheter with a proximal funnel opening that will accommodate the Luer lock adapter. - Use only catheters made of vinyl/PVC (uncoated or coated with hydrogel), red rubber latex or silicone to instill ADSTILADRIN. Do not use catheters coated or embedded with silver or antibiotics. 1.

Dosage forms and strengths

3 DOSAGE FORMS AND STRENGTHS ADSTILADRIN is a sterile, clear to opalescent suspension for intravesical instillation, supplied as single-use vials. ADSTILADRIN is provided in a carton containing four (4) vials. All vials have a nominal concentration of 3 × 10 11 viral particles (vp)/mL. Each vial of ADSTILADRIN contains an extractable volume of not less than 20 mL. ADSTILADRIN is a suspension for intravesical instillation, supplied as single-use vials. ( 3 ) ADSTILADRIN is provided in a carton containing four (4) vials. All vials have a nominal concentration of 3 × 10 11 viral particles (vp)/mL. Each vial of ADSTILADRIN contains an extractable volume of not less than 20 mL. ( 3 )

Contraindications

4 CONTRAINDICATIONS ADSTILADRIN is contraindicated in patients with prior hypersensitivity reactions to interferon alfa or to any component of the product [ see Description (11) ]. ADSTILADRIN is contraindicated in patients with hypersensitivity to interferon alfa or any component of the product. ( 4 )

Warnings and precautions

Delaying cystectomy could lead to the development of metastatic bladder cancer, which can be lethal. ( 5.1 ) Risk of disseminated adenovirus infection: Persons who are immunocompromised or immunodeficient may be at risk for disseminated infection from ADSTILADRIN due to low levels of replication-competent adenovirus. Avoid ADSTILADRIN exposure to immunocompromised or immunodeficient individuals. ( 5.2 ) 5.1 Risk of Muscle Invasive or Metastatic Bladder Cancer with Delayed Cystectomy Delaying cystectomy in patients with BCG-unresponsive CIS could lead to development of muscle invasive or metastatic bladder cancer, which can be lethal. The risk of developing muscle-invasive or metastatic bladder cancer increases the longer cystectomy is delayed in the presence of persisting CIS. Of the patients with CIS treated with ADSTILADRIN on Study CS-003 who underwent subsequent radical cystectomy and for whom pathologic data were available, 14% (n = 6) had muscle-invasive (T2 or greater) disease at cystectomy. Median 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 undergo cystectomy experienced progression to muscle-invasive disease during the treatment period. If patients with CIS do not have a complete response to treatment after 3 months or if CIS recurs, consider cystectomy. 5.2 Risk of Disseminated Adenovirus Infection Immunocompromised persons, including those receiving immunosuppressant therapy, may be at risk for disseminated adenovirus infection because of the possible presence of low levels of replication-competent adenovirus in ADSTILADRIN. Individuals who are immunosuppressed or immune-deficient should not come into contact with ADSTILADRIN.

Side effects

The most common (>10%) adverse reactions, including laboratory abnormalities (>15%), were glucose increased, instillation site discharge, triglycerides increased, fatigue, bladder spasm, micturition (urination urgency), creatinine increased, hematuria (blood in urine), phosphate decreased, chills, pyrexia (fever), and dysuria (painful urination). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Ferring Pharmaceuticals at 1-888-337-7464 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 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. The safety of ADSTILADRIN was evaluated in Study CS-003, a multicenter, single-arm, open-label study in 157 U.S. patients [ see Clinical Studies (14 ) ] with high-risk BCG‑unresponsive NMIBC, 107 of whom had BCG-unresponsive carcinoma in situ (CIS) with or without papillary tumors. Patients received 75 mL (3 x 10 11 vp/mL) ADSTILADRIN administered intravesically once every 3 months for up to 12 months [ see Clinical Studies (14 ) ]. All patients with an absence of high-risk recurrence or progression were offered continued treatment every 3 months beyond 12 months. The median number of instillations of ADSTILADRIN was 2 (range 1 to 5). Serious adverse reactions occurred in 11% of patients who received ADSTILADRIN. Serious adverse reactions occurring in >1% of patients included coronary artery disease and hematuria (blood in urine). Permanent discontinuation of ADSTILADRIN due to an adverse reaction occurred in 3 (1.9%) patients. Adverse reactions that resulted in permanent discontinuation of ADSTILADRIN included bladder spasm instillation site discharge, and benign neoplasm of the bladder. Dosage interruptions of ADSTILADRIN due to an adverse reaction occurred in 54 (34%) patients. Adverse reactions in >10% of patients that required dosage interruption included instillation site discharge, bladder spasm, and micturition urgency. The most common (>10%) adverse reactions, including laboratory abnormalities (>15%), were glucose increased, instillation site discharge, triglycerides increased, fatigue, bladder spasm, micturition (urination) urgency, creatinine increased, hematuria (blood in urine), phosphate decreased, chills, dysuria, and pyrexia (fever). Tables 1 and 2 summarize adverse reactions and laboratory abnormalities, respectively, in patients on ADSTILADRIN in CS-003. Clinically relevant adverse reaction in <10% of patients who received ADSTILADRIN include syncope (fainting) (1.3%). Table 1: Adverse Reactions (>10%) in Patients with NMIBC in CS-003 Adverse Reaction Graded per NCI CTCAE v4.03; there were no Grade 4 or 5 reactions. ADSTILADRIN Grade 1 and 2 (n=157) % ADSTILADRIN Grade 3 (n=157)% General disorders and administration site conditions - - Instillation site discharge 33 0 Fatigue 24 0 Pyrexia 16 0 Chills 15 0 Renal and urinary disorders - - Bladder spasm 20 1 Micturition urgency 19 1 Hematuria 17 1 Dysuria 16 0 Clinically relevant adverse reactions in <10% of patients who received ADSTILADRIN included coronary artery disease (1.3%), acute coronary syndrome (1.3%), atrial fibrillation (1.3%), dehydration (1.3%), hypoglycemia (low blood sugar) (1.3%), syncope (fainting) (1.3%), heart failure (0.6%), pericarditis, (0.6%), brain edema (swelling) (0.6%), bile duct stone (0.6%), and sepsis (0.6%). Table 2 summarizes the laboratory abnormalities in CS-003. Table 2: Selected Laboratory Abnormalities (>15.0%) That Worsened from Baseline in Patients with NMIBC in CS-003 Laboratory Abnormality ADSTILADRIN The denominator used to calculate the rate varied from 148 to 156 based on the number of patients with a baseline value and at least one post-treatment value. (All Grades, %) ADSTILADRIN (Grade 3 or 4, %) Chemistry - - Glucose increased 38 6 Triglycerides increased 30 1.9 Creatinine increased 17 0 Phosphate decreased 16 1.4 Hematology - - Hemoglobin decreased 16 0.6

Use in specific populations

Immunocompromise/immunodeficiency: Avoid in patients with immunocompromise or immunodeficiency. ( 8 ) 8.1 Pregnancy Risk Summary Adequate and well-controlled studies with ADSTILADRIN have not been conducted in pregnant women. Animal reproductive and developmental toxicity studies have not been conducted with ADSTILADRIN. Advise pregnant women of the potential risk to a 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. 8.2 Lactation Risk Summary There is no information regarding the presence of ADSTILADRIN in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for ADSTILADRIN and any potential adverse effects on the breastfed infant from ADSTILADRIN or from the underlying maternal condition. 8.3 Females and Males of Reproductive Potential No nonclinical or clinical studies were performed to evaluate the effect of ADSTILADRIN on fertility. Pregnancy Testing Verify pregnancy status in females of reproductive potential prior to initiating ADSTILADRIN. Contraception Females Advise females of reproductive potential to use effective contraception during treatment with ADSTILADRIN and for 6 months following the last dose. Males Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ADSTILADRIN and for 3 months following the last dose. 8.4 Pediatric Use Safety and effectiveness of ADSTILADRIN in pediatric patients have not been established. 8.5 Geriatric Use Clinical studies of ADSTILADRIN in BCG-unresponsive high-risk NMIBC with CIS did not include sufficient numbers of patients younger than 65 years of age to determine whether safety and effectiveness differ from older patients. 8.6 Gender-specific Use In clinical studies with ADSTILADRIN, no overall differences in safety or efficacy were observed between females and males.

Pregnancy

8.1 Pregnancy Risk Summary Adequate and well-controlled studies with ADSTILADRIN have not been conducted in pregnant women. Animal reproductive and developmental toxicity studies have not been conducted with ADSTILADRIN. Advise pregnant women of the potential risk to a 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.

Pediatric use

8.4 Pediatric Use Safety and effectiveness of ADSTILADRIN in pediatric patients have not been established.

Geriatric use

8.5 Geriatric Use Clinical studies of ADSTILADRIN in BCG-unresponsive high-risk NMIBC with CIS did not include sufficient numbers of patients younger than 65 years of age to determine whether safety and effectiveness differ from older patients.

Description

(nadofaragene firadenovec-vncg) is a non-replicating adenoviral vector-based gene therapy for intravesical instillation. It is a recombinant adenovirus serotype 5 vector containing a transgene encoding the human interferon alfa-2b (IFNα2b). ADSTILADRIN has a nominal concentration of 3 x 10 11 vp/mL. A single-use vial of ADSTILADRIN contains an extractable volume of 20 mL and the following excipients: [N-(3-cholamidopropyl)-N-(3-lactobionamidopropyl)]-cholamide (Syn3) (0.95 mg/mL), citric acid monohydrate (0.01 mg/mL), glycerol (84 mg/mL), hydroxypropyl-beta-cyclodextrin (7.9 mg/mL), magnesium chloride hexahydrate (0.34 mg/mL), polysorbate 80 (Tween 80) (0.48 mg/mL), sodium dihydrogen phosphate dihydrate (1.4 mg/mL), sucrose (17 mg/mL), tri-sodium citrate dihydrate (0.04 mg/mL), tromethamine (1.4 mg/mL) and Water for Injection (q.s. 1 mL). ADSTILADRIN is a sterile, clear to opalescent suspension, and contains no preservative.

Mechanism of action

12.1 Mechanism of Action ADSTILADRIN is a non-replicating adenoviral vector-based gene therapy designed to deliver a copy of a gene encoding a human interferon-alfa 2b (IFNα2b) to the bladder urothelium. Intravesical instillation of ADSTILADRIN results in cell transduction and transient local expression of the IFNα2b protein that is anticipated to have anti-tumor effects.

How supplied

16 HOW SUPPLIED/STORAGE AND HANDLING ADSTILADRIN is shipped frozen at ≤ -60°C (≤ -76°F) in an insulated shipping box that will maintain the required temperature for a minimum of 72 hours after being sealed. Each carton (NDC 55566-1050-1) contains a removable cardboard nest of four (4) clear glass vials of ADSTILADRIN. Each vial contains a sterile frozen suspension with an extractable volume of 20 mL and is either sealed with a bromobutyl rubber stopper and a tamper-evident aluminum crimp (NDC 55566-1050-0) or with a bromobutyl rubber stopper embedded within a press-fit closure (NDC 55566-1050-2). Upon receipt, cartons of ADSTILADRIN can be stored as indicated below: In a freezer ≤ -60°C (≤ -76°F) until expiry date printed on the carton. In a freezer between -25°C to -15°C (-13°F to 5°F) up to 3 months, without exceeding the original expiry date printed on the vial and outer carton. When stored in freezer, the date of placement in freezer should be noted. In addition, the date for when the carton should be discarded if not used, must be written on the outer carton. These dates should be three months apart but should not past the original expiry date. This discard date supersedes the original expiry date. When thawed, ADSTILADRIN is a clear to opalescent suspension, with nominal concentration of 3 × 10 11 viral particles (vp)/mL. Prior to use, ADSTILADRIN must be brought to room temperature (20°C to 25°C [68°F to 77°F]). ADSTILADRIN may be stored for up to 24 hours at room temperature and a total of up to 7 days refrigerated at 2°C to 8°C (36°F to 46°F), including thawing time. After withdrawing the suspension into syringes, the syringes may be stored for up to 6 hours at room temperature (20°C to 25°C [68°F to 77°F]).
• Protect the vials from light. [ see Dosage and Administration (2.2 ) ].
• DO NOT REFREEZE
• ADSTILADRIN is a non-replicating adenoviral vector-based gene therapy. Follow universal biosafety precautions for handling [ see Dosage and Administration (2.2 ) ].
• Dispose of unused product and disposable materials that may have come in contact with ADSTILADRIN in accordance with local biosafety guidelines applicable for handling and disposal of the biohazard waste.

Patient information

Risk of Metastatic Bladder Cancer with Delayed Cystectomy Inform patients that delaying cystectomy in patients with BCG-unresponsive CIS could lead to development of muscle-invasive or metastatic bladder cancer. Discuss the risk of muscle-invasive or metastatic bladder cancer and that the risk increases the longer cystectomy is delayed in the presence of persisting CIS [ see Warnings and Precautions (5.1) ] . Risk of Disseminated Adenovirus Infection Inform patients and their caregivers that treatment or contact with ADSTILADRIN in those who are immunocompromised, including those receiving immunosuppressive therapy, may increase the risk for disseminated adenovirus infection [ see Warnings and Precautions (5.2) ] . Shedding of ADSTILADRIN Inform patients and their caregivers that transient and low‑level shedding of ADSTILADRIN may occur in urine. Instruct patients and their caregivers that for 2 days following treatment, voided urine should be disinfected for 15 minutes with an equal volume of bleach before flushing [ see Dosage and Administration (2.2) ] . Manufactured for: Ferring Pharmaceuticals 2770 Kastrup, Denmark U.S. License No. 2222 ADSTILADRIN®, Ferring and the Ferring Pharmaceuticals logo are trademarks of Ferring. XXXXXXXXXX

Label text from the FDA structured product label by Ferring Pharmaceuticals Inc. (revised Mar 24, 2026). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Nadofaragene Firadenovec in 1 product

Adstiladrin NDC products (1)

NDC	Strength & form	Labeler	Type
55566-1050	Nadofaragene Firadenovec 300000000000 {VP}/mL Suspension	Ferring Pharmaceuticals Inc.	BLA

Frequently asked questions

What is Adstiladrin used for?

What are the side effects of Adstiladrin?

Who makes Adstiladrin?

Adstiladrin is listed by 1 labeler in the FDA NDC directory, including Ferring Pharmaceuticals Inc..