Nadofaragene Firadenovec-vncg (Monograph)

Brand name: Adstiladrin
Drug class: Gene Therapy

Medically reviewed by Drugs.com on Dec 17, 2023. Written by ASHP.

Introduction

Nadofaragene firadenovec-vncg is a non-replicating adenoviral vector-based gene therapy.

Uses for Nadofaragene Firadenovec-vncg

Nadofaragene firadenovec-vncg has the following uses:

Nadofaragene firadenovec-vncg 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.

Efficacy of nadofaragene firadenovec-vncg was evaluated in an open-label, multicenter, single-arm trial (CS-003) in adults with BCG-unresponsive, high-risk, non-muscle invasive bladder cancer with carcinoma in situ (CIS) with or without papillary tumors. Prior to treatment, all patients had undergone transurethral resection of bladder tumor to remove all resectable disease. Patients received nadofaragene firadenovec-vncg 75 mL intravesical instillation (3 x 10¹¹ viral particles) once every 3 months for up to 12 months or until unacceptable toxicity or recurrent high-grade NMIBC occurred. The complete response rate (defined by negative results for cystoscopy and urine cytology) was 51% and median duration of response in responders was 9.7 months.

Nadofaragene Firadenovec-vncg Dosage and Administration

General

Nadofaragene firadenovec-vncg is available in the following dosage form(s) and strength(s):

Suspension for intravesical instillation, supplied as single-use vials.

Commercially available in a carton containing four (4) vials. All vials have a nominal concentration of 3 × 10¹¹ viral particles (vp)/mL. Each vial of nadofaragene firadenovec-vncg contains an extractable volume of not less than 20 mL.

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

Premedication with an anticholinergic is recommended before each instillation of nadofaragene firadenovec-vncg.
Administer nadofaragene firadenovec-vncg by intravesical instillation only. Follow universal biosafety precautions for handling.
Nadofaragene firadenovec-vncg is not for intravenous use, topical use, or oral administration.
The recommended dose of nadofaragene firadenovec-vncg is 75 mL at a concentration of 3 x 10¹¹ viral particles (vp)/mL, instilled once every three (3) months into the bladder via a urinary catheter.
After the instillation, allow nadofaragene firadenovec-vncg to be left in the bladder for 1 hour. During the 1 hour dwell time, the patient should reposition approximately every 15 minutes.
See Full Prescribing information for additional instructions on preparation and administration of nadofaragene firadenovec-vncg.

Cautions for Nadofaragene Firadenovec-vncg

Contraindications

Nadofaragene firadenovec-vncg is contraindicated in patients with hypersensitivity to interferon alfa or any component of the product.

Warnings/Precautions

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 carcinoma in situ (CIS) treated with nadofaragene firadenovec-vncg in 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.

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 nadofaragene firadenovec-vncg. Individuals who are immunosuppressed or immune-deficient should not come into contact with nadofaragene firadenovec-vncg.

Specific Populations

Pregnancy

Adequate and well-controlled studies with nadofaragene firadenovec-vncg have not been conducted in pregnant women. Animal reproductive and developmental toxicity studies have not been conducted with nadofaragene firadenovec-vncg. 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.

Lactation

There is no information regarding the presence of nadofaragene firadenovec-vncg 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 nadofaragene firadenovec-vncg and any potential adverse effects on the breastfed infant from nadofaragene firadenovec-vncg or from the underlying maternal condition.

Females and Males of Reproductive Potential

No nonclinical or clinical studies were performed to evaluate the effect of nadofaragene firadenovec-vncg on fertility.

Verify pregnancy status in females of reproductive potential prior to initiating nadofaragene firadenovec-vncg.

Advise females of reproductive potential to use effective contraception during treatment with nadofaragene firadenovec-vncg and for 6 months following the last dose.

Advise male patients with female partners of reproductive potential to use effective contraception during treatment with nadofaragene firadenovec-vncg and for 3 months following the last dose.

Pediatric Use

Safety and effectiveness of nadofaragene firadenovec-vncg in pediatric patients have not been established.

Geriatric Use

Clinical studies of nadofaragene firadenovec-vncg 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.

Gender-specific Use

In clinical studies with nadofaragene firadenovec-vncg, no overall differences in safety or efficacy were observed between females and males.

Common Adverse Effects

The most common (>10%) adverse reactions, including laboratory abnormalities (>15%), were increased glucose, instillation site discharge, increased triglycerides, fatigue, bladder spasm, micturition (urination urgency), increased creatinine, hematuria (blood in urine), decreased phosphate, chills, pyrexia (fever), and dysuria (painful urination).

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

Actions

Mechanism of Action

Nadofaragene firadenovec-vncg 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 nadofaragene firadenovec-vncg results in cell transduction and transient local expression of the IFNα2b protein that is anticipated to have anti-tumor effects.

Advice to Patients

Inform patients that delaying cystectomy in patients with BCG-unresponsive carcinoma in situ (CIS) could lead to development of muscle-invasive or metastatic bladder cancer. Discuss the risk of muscle-invasive or metastatic bladder cancer with patients and inform them that the risk increases the longer cystectomy is delayed in the presence of persisting CIS.
Inform patients and their caregivers that treatment or contact with nadofaragene firadenovec-vncg in those who are immunocompromised, including those receiving immunosuppressive therapy, may increase the risk for disseminated adenovirus infection.
Inform patients and their caregivers that transient and low-level shedding of nadofaragene firadenovec-vncg may occur in urine. Instruct patients and their caregivers that for 2 days following treatment, voided urine should be disinfected for 30 minutes with an equal volume of bleach before flushing.

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.