Background

Nadofaragene firadenovec-vncg (e.g., Adstiladrin) is a non-replicating adenoviral vector-based gene therapy designed to deliver a copy of a gene encoding a human interferon-alfa 2b to the bladder urothelium after administration intravesically into the bladder. Nadofaragene firadenovec-vncg is indicated for the treatment of adult individuals with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive nonmuscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors. 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.

Policy (Criteria)

Nadofaragene firadenovec-vncg for the treatment of Bladder Cancer is considered MEDICALLY NECESSARY when ALL of the following criteria are met:

1. Patient has a diagnosis of non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (with or without papillary tumors); AND
2. Patient has high-risk disease that is unresponsive to Bacillus Calmette - Guerin (BCG) defined as:
   1. Persistent disease following adequate BCG therapy of at least five (5) of six (6) doses of an initial induction course of BCG followed by at least two (2) of three (3) doses of maintenance therapy or two (2) of six (6) doses of an additional induction course; OR
   2. Disease recurrence after an initial tumor-free state following adequate BCG therapy of at least five (5) of six (6) doses of an initial induction course of BCG followed by at least two (2) of three (3) doses of maintenance therapy or two (2) of six (6) doses of an additional induction course; OR
   3. Stage T1 disease following a single induction course of BCG; AND
3. Patient has undergone transurethral resection of bladder tumor (TURBT) to remove all resectable disease (Ta and T1 components); AND
4. Patient does NOT have extra-vesical (i.e., urethra, ureter, or renal pelvis), muscle invasive (T2 - T4), or metastatic urothelial carcinoma; AND
5. Individual is not currently receiving systemic therapy for bladder cancer; AND
6. Individual has not received any prior treatment with adenovirus-based therapies; AND
7. Patient does not have a hypersensitivity to interferon alfa; AND
8. Patient is not immunosuppressed or immunodeficient.

Renewal Criteria

Due to the increased risk of developing muscle - invasive or metastatic bladder cancer with delay in cystectomy, if patients with CIS do not have a complete response to treatment with Adstiladrin (Nadofaragene firadenovec-vncg) after 3 months or if CIS recurs, consider cystectomy.

Nadofaragene firadenovec-vncg approval can be renewed for continuation of care when ALL the following criteria are met:

1. Continues to meet initial approval criteria; AND
2. Disease response with treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread; AND
3. Absence of unacceptable toxicity from the drug such as but not limited to disseminated adenovirus infection; AND
   1. For first renewal request, the patient had a complete response (CR) to initial therapy defined as a negative result for cystoscopy [ with TURBT/biopsies as applicable ] and urine cytology; OR
   2. For subsequent renewals the patient has not experienced a high-grade or CIS recurrence.

The use of Adstiladrin (nadofaragene firadenovec-vncg) for any other oncologic indication is considered INVESTIGATIONAL and therefore, not covered.

References

1. Boorjian SA, Alemozaffar M, Konety BR, et.al.(2021) Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, openlabel, repeat-dose clinical trial. Lancet Oncol. 2021 Jan;22(1):107-117. doi: 10.1016/S1470-2045(20)30540-4. Epub 2020 Nov 27. PMID: 33253641; PMCID: PMC7988888.
2. Nadofaragene firadenovec-vncg [package insert]. Kupio, Finland: Ferring Pharmaceuticals; 2022
3. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Bladder Cancer (Version 2.2022). Available at http://www.nccn.org. ©National Comprehensive Cancer Network, 2022 Access May 10, 2023
4. Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP.(1982) Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-655. PMID: 7165009.
5. Shore ND, Boorjian SA, Canter DJ, et.al.(2017) Intravesical rAd-IFNa/Syn3 for Patients With High-Grade, Bacillus Calmette-Guerin-Refractory or Relapsed Non-Muscle-Invasive Bladder Cancer: A Phase II Randomized Study. J Clin Oncol. 2017 Oct 20;35(30):3410-3416. doi:10.1200/JCO. 2017.72.3064 . Epub 2017 Aug 23. Erratum in: J
6. Adstiladrin® (nadofaragene firadenovec-vncg), suspension for intravesical use [package insert]. Ferring Pharmaceuticals. Kastrup, Denmark. Revised 08/2024.
7. Clinical PharmacologyTM Compendium. 2025. Tampa FL: Gold Standard, Inc. Nadofaragene firadenovec-vncg.
8. Micromedex DrugDex Compendium®. 2025. Nadofaragene firadenovec-vncg.
9. National Comprehensive Cancer Network (NCCN). Nadofaragene firadenovecvncg. NCCN Drugs and Biologics Compendium®. 2025.
10. Nadofaragene firadenovec-vncg In: AHFS Drug Information Online Electronic Medical Library. Bethesda, MD: American Society of Health-System Pharmacists. Updated December 17, 2023.

Coding Section

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each Policy. They may not be all-inclusive.

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines.

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