- U.S. Food and Drug Administration (FDA) (https://voice.ons.org/topic/us-food-and-drug-administration-fda)
- Drug Reference Sheet (https://voice.ons.org/topic/drug-reference-sheet)
- Oncology drug research (https://voice.ons.org/topic/oncology-drug-research)
- Clinical practice (https://voice.ons.org/topic/clinical-practice)
Oncology Drug Reference Sheet: Nadofaragene Firadenovec-Vncg
Under the U.S. Food and Drug Administration’s (FDA’s) fast-track approval process, nadofaragene firadenovec-vncg (Adstiladrin®) became the first gene therapy approved for the treatment (https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-first-adenoviral-vector-based-gene-therapy-high-risk-bacillus-calmette-guerin) of high-risk non-muscle invasive bladder cancer. Approximately 75% of newly diagnosed bladder cancers (https://pubmed.ncbi.nlm.nih.gov/32760227/) are classified as non-muscle invasive. Bacillus Calmette Guérin (BCG) has been used as first-line therapy for more than 20 years, but eventually 30%–50% of patients stop responding (https://www.urologytimes.com/view/bcg-unresponsive-nmibc-current-evidence-and-options), and nadofaragene firadenovec-vncg offers a new treatment option. FDA’s December 2022 approval (https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-first-adenoviral-vector-based-gene-therapy-high-risk-bacillus-calmette-guerin) was based on complete response (CR) and duration of response from Study CS-003, which demonstrated a 46% CR for at least one year.
Non-replicating adenoviral vector-based gene therapy
Mechanism of Action
Nadofaragene firadenovec-vncg delivers a copy of a gene (https://www.fda.gov/media/164029/download) that encodes for an antitumor protein. Once instilled, the gene creates a localized expression of the protein directly in the bladder urothelium, exposing the cancer cells to the protein for an extended period of time.
Treatment of adult patients with high-risk, BCG-unresponsive, non-muscle invasive bladder cancer (https://www.fda.gov/media/164029/download) with carcinoma in situ with or without papillary tumors
75 ml of nadofaragene firadenovec-vncg at a concentration of 3 x 1,011 viral particles (vp)/ml, instilled once every three months (https://www.fda.gov/media/164029/download)
Administer via intravesical instillation only. Specific administration training may be required. The full instillation process can be found on page 4 of the package insert (https://www.fda.gov/media/164029/download).
- Premedicate patients with an anticholinergic drug before each instillation.
- Maintain nadofaragene firadenovec-vncg in the bladder for one hour.
- During the one-hour dwell time, reposition the patient every 15 minutes from left to right and back to front to maximize bladder surface exposure.
- If a patient experiences bladder cramping or premature voiding, adjust their position or discontinue the dwell time.
Additional administration information is available on pages 2–4 in the package insert (https://www.fda.gov/media/164029/download).
During the drug’s clinical trials, more than 10% of patients reported (https://www.fda.gov/media/164029/download) instillation site discharge, fatigue, bladder spasm, micturition, hematuria, chills, pyrexia, and dysuria. More than 15% experienced (https://www.fda.gov/media/164029/download) increased glucose, triglyceride, and creatinine and decreased phosphate levels.
- Obtain a pregnancy test from patients of reproductive potential.
- Review potential side effects with patients.
- Describe the instillation process and what they can expect.
After administration (https://www.fda.gov/media/164029/download), ensure patients and caregivers understand the safe-handling precautions to follow at home and when to call the healthcare team.
Delayed cystectomy may increase your risk (https://www.fda.gov/media/164029/download) for metastatic bladder cancer. All patients and their partners of reproductive potential should use contraception during and for six months following treatment (https://www.fda.gov/media/164029/download) with nadofaragene firadenovec-vncg. You may shed low levels of the medication (https://www.fda.gov/media/164029/download) in your urine for up to two days following treatment. Disinfect your urine for 30 minutes with an equal volume of bleach before flushing.
Nadofaragene firadenovec-vncg is not recommended (https://www.fda.gov/media/164029/download) for patients who:
- Have experienced hypersensitivity to interferon alfa or any component of the product
- Are immunocompromised because of risk for disseminated adenovirus infection
No information is available about the effects for pregnant patients and their fetus or breastfed infants of patients receiving nadofaragene firadenovec-vncg. Study populations (https://www.fda.gov/media/164029/download) were mostly aged 65 or older, and no conclusions can be drawn about safety or efficacy in younger age groups. No significant sex-based differences were noted (https://www.fda.gov/media/164029/download).
Follow hazardous drug safe handling practices and medication exposure precautions. Because of the risk for splashing, wear an eye and face shield (https://www.ons.org/clinical-practice-resources/toolkit-safe-handling-hazardous-drugs-nurses-oncology) in addition to standard hazardous drug administration personal protective equipment. Treat any spills (https://www.fda.gov/media/164029/download) with a virucidal agent (e.g., sodium hypochlorite with 0.5% active chlorine, 6% hydrogen peroxide solution) for 30 minutes. Dispose materials (https://www.fda.gov/media/164029/download) that have contacted nadofaragene firadenovec-vncg in biohazard containers. Decontaminate nondisposable equipment (https://www.fda.gov/media/164029/download) according to your facility’s standard operating procedures.