ADSTILADRIN

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

ADSTILADRIN is contraindicated in patients with prior hypersensitivity reactions to interferon alfa or to any component of the product [

ADSTILADRIN (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

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.

The efficacy of ADSTILADRIN was evaluated in CS-003 (NCT02773849), an open-label, multicenter, single-arm trial in 103 adults with BCG-unresponsive, high-risk, non-muscle invasive bladder cancer with carcinoma in situ (CIS) with or without papillary tumors following transurethral resection, of whom 98 were considered evaluable for response. BCG-unresponsive high-risk NMIBC was defined as persistent disease following adequate BCG therapy, disease recurrence after an initial tumor-free state following adequate BCG therapy, or T1 disease following a single induction course of BCG. Adequate BCG was defined as the administration of at least five of six doses of an initial induction course plus either of: at least two of three doses of maintenance therapy or at least two of six doses of a second induction course. Prior to treatment, all patients had undergone transurethral resection of bladder tumor (TURBT) to remove all resectable disease (Ta and T1 components). Residual CIS (Tis components) not amenable to complete resection was allowed. The trial excluded patients with extra-vesical (i.e., urethra, ureter, or renal pelvis), muscle invasive (T2-T4), or metastatic urothelial carcinoma.

Patients received ADSTILADRIN 75 mL intravesical instillation (3 x 10

The major efficacy outcome measures were complete response (CR) at any time (as defined by negative results for cystoscopy [with TURBT/biopsies as applicable] and urine cytology) and duration of response. Low-grade (Ta) papillary disease was not considered a recurrence for the purposes of evaluating CR. CR was assessed at 3, 6, 9, and 12 months by cystoscopy and cytology. Random bladder biopsy of five sites was conducted in patients remaining in CR at Month 12.  Assessment of durability of CR subsequent to these evaluations was performed per local standards of care.

The evaluable CIS study population characteristics were median age of 70 (range 44-89) with 32% >75 years of age; 88% male, 92% White. Tumor pattern at study entry was CIS with T1 (5%), CIS with high-grade Ta (19%), and CIS (76%). The median number of instillations of prior BCG was 12 (range 8 to 18).

Efficacy results are summarized in Table 3.

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:

When thawed, ADSTILADRIN is a clear to opalescent suspension, with nominal concentration of 3 × 10

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. [

•   DO NOT REFREEZE

•   ADSTILADRIN is a non-replicating adenoviral vector-based gene therapy. Follow universal biosafety precautions for handling [

•   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.

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 [

Manufactured for:

Ferring Pharmaceuticals

U.S. License No. 2222

ADSTILADRIN®, Ferring and the Ferring Pharmaceuticals logo are trademarks of Ferring.

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NDC 55566-1050-1

Sterile suspension

U.S. Licence No. 2222