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Nadofaragene Firadenovec-vncg (Adstiladrin®)
08.02.11b

Policy

MEDICALLY NECESSARY


INITIATION THERAPY 

Nadofaragene firadenovec-vncg (Adstiladrin) is considered medically necessary and, therefore, covered in individuals 18 years and older for the treatment of high-risk non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors for the first two doses when ALL of the following criteria are met:

  • Individual has Bacillus Calmette-Gué​​rin (BCG)-unresponsive* disease, defined as persistent or recurrent disease following adequate BCG therapy:**
    • ​As initial management 
    • As recurrent or persistent disease that is cytology-positive, imaging- and cystoscopy-negative, and bladder positive
  • ​​All visible papillary tumors for the individual have been resected and those with persistent T1 disease on transurethral resection of bladder tumor (TURBT) have undergone an additional re-TURBT within 14 to 60 days prior to beginning nadofaragene firadenovec-vncg (Adstiladrin).
  • Individual does not have concomitant upper tract urothelial carcinoma or urothelial carcinoma within the prostatic urethra.
  • Individual is not currently receiving systemic therapy for bladder cancer.
  • Individual has not received any prior treatment with adenovirus-based therapies.
*High-grade T1 at the first evaluation following induction BCG (3 months); recurrent high-grade Ta/T1 within 6 months of adequate BCG treatment; or recurrent CIS within 12 months of the last adequate BCG treatment.

​**Adequate BCG therapy defined as having received at least two previous courses of BCG within a 12-month period defined as either: 

  • At least five of six induction BCG instillations AND at least two of three instillations of maintenance BCG; or 
  • ​At least two of six instillations of a second induction course where maintenance BCG is not given​.

CONTINUATION THERAPY

Continued therapy with nadofaragene firadenovec-vncg (Adstiladrin) is considered medically necessary and, therefore, covered when ALL of the following criteria are met while on the current regimen:

  • There is no unacceptable toxicity.
  • Clinical documentations demonstrate that the individual continues to show a positive clinical response to therapy (i.e., absence of recurrent high-grade NMIBC).
    • Positive clinical response can be reported through any of the following methods:​
      • ​Urine cytology reports as normal, atypical, degenerative, reactive, inflammatory, or nonspecific AND cystoscopy reports as normal or with findings that did not include evidence of low-grade or high-grade recurrence OR
      • Bladder biopsy, if performed, demonstrates an absence of low-grade or high-grade recurrence.

MANDATES ​

 

PENNSYLVANIA MEMBERS
In accordance with the Commonwealth of Pennsylvania's Act 6 of 2020 or Fair Access to Cancer Treatment Act, for members who are enrolled in Pennsylvania commercial products who have stage 4, advanced metastatic cancer, refer to the Medical Policy titled "Coverage of Anticancer Prescription Oral and Injectable Drugs and Biologics and Supportive Agents" (08.01.08) for additional information regarding the applicable coverage of drugs and biologics.​​

​

EXPERIMENTAL/INVESTIGATIONAL 

All other uses for nadofaragene firadenovec-vncg (Adstiladrin) are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company medical policy on off-label coverage for prescription drugs and biologics.​


REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but​ are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.

Guidelines

BLACK BOX WARNINGS


Refer to the specific manufacturer's prescribing information for any applicable Black Box Warnings. 


DRUG INFORMATION


​Nadofaragene firadenovec-vncg (Adstiladrin) is intravesical instillation only. The dose is 75 mL of nadofaragene firadenovec-vncg (Adstiladrin) at a concentration of 3 × 1011 viral particles (vp)/mL, instilled once every 3 months.​

 

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, nadofaragene firadenovec-vncg (Adstiladrin) is covered under the medical benefits of the Company’s products when the medical necessity criteria listed in this medical policy are met.​

​MANDATES​

This policy is consistent with applicable state mandates. The laws of the state where the group benefit contract is issued determine the mandated coverage.​

 

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS


On December 16, 2022, the FDA granted approval for nadofaragene firadenovec-vncg (Adstiladrin) 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. 

 

PEDIATRIC USE

The safety and effectiveness of nadofaragene firadenovec-vncg (Adstiladrin) have not been established in pediatric individuals less than 18 years of age.​​​​

Description

BLADDER CANCER  


Bladder cancer is one of the more common forms of cancer. Approximately 75% to 80% of newly diagnosed bladder cancers are classified as non-muscle invasive bladder cancer (NMIBC)—a type of cancer that has grown through the lining of the bladder but has not yet invaded the muscle layer. NMIBC is associated with high rates of recurrence (between 30% and 80%) and the risk of progression to invasive and metastatic disease. Treatment and care of individuals with high-risk NMIBC, including those with carcinoma in situ (CIS), often involves removing the tumor followed by Bacillus Calmette-Guérin (BCG) bladder instillation therapy to reduce the risk of recurrence. Few effective treatment options exist for patients who develop BCG-unresponsive disease. The failure to achieve a complete response, or the disappearance of all signs of cancer as seen on cystoscopy, biopsied tissue, and urine, is associated with an increased risk of death or a disease-worsening event. 

 

NADOFARAGENE FIRADENOVEC-VNCG (ADSTILADRIN)

 

Nadofaragene firadenovec-vncg (Adstiladrin) is a novel adenovirus vector–based gene therapy. It is designed to deliver a copy of the interferon-alfa 2b (IFNα2b) gene to the bladder urothelium, leading to transient local expression of IFNα2b, which is thought to have anti-tumor effects. 

 

PEER-REVIEWED LITERATURE 


SUMMARY

The safety and effectiveness of nadofaragene firadenovec-vncg (Adstiladrin)​ was evaluated in the Phase 03 CS-003 trial (NCT02773849: ADSTILADRIN (=INSTILADRIN) in Patients With High Grade, Bacillus Calmette-Guerin (BCG) Unresponsive Non-Muscle Invasive Bladder Cancer (NMIBC)), an open-label, multicenter, single-arm study that enrolled 157 adult individuals with BCG-unresponsive, high-risk NMIBC following transurethral resection. Among these individuals, 103 had carcinoma in situ (CIS) with or without papillary tumors, of which 98 were considered evaluable for response. Nadofaragene firadenovec-vncg (Adstiladrin)​ was administered directly into the individual's bladder by instillation once every 3 months. The trial met its primary endpoint, with more than half (51%) of the 98 evaluable individuals (95% confidence interval [CI], 41–61) with CIS with or without concomitant high-grade Ta or T1 disease (CIS ± Ta/T1) achieving a complete response (CR), all by 3 months. Of the individuals who achieved an initial CR, 46% (n=23 of 50) continued to remain free of high-grade recurrence at 12 months. Safety analyses were done in all individuals who received at least one dose of treatment. Serious adverse reactions (SARs) occurred in 11% of individuals who received nadofaragene firadenovec-vncg (Adstiladrin). SARs occurring in more than 1% of individuals included coronary artery disease and hematuria (blood in urine). Permanent discontinuation of nadofaragene firadenovec-vncg (Adstiladrin) due to an adverse reaction (AR) occurred in three individuals (1.9%). ARs that resulted in permanent discontinuation included bladder spasm instillation site discharge and benign neoplasm of the bladder. Dosage interruptions of nadofaragene firadenovec-vncg (Adstiladrin)​ due to an AR occurred in 54 (34%) individuals. ARs in more than 10% of individuals that required dosage interruption included instillation site discharge, bladder spasm, and micturition (urination) urgency. The most common (>10%) ARs, including laboratory abnormalities (>15%), were increased glucose, instillation site discharge, increased triglycerides, fatigue, bladder spasm, micturition urgency, increased creatinine, hematuria, phosphate decreased, chills, dysuria, and pyrexia (fever).​

OFF-LABEL INDICATIONS  

There may be additional indications contained in the Policy section of this document due to the evaluation of criteria highlighted in the Company's off-label policy, and/or review of clinical guidelines issues by leading professional organizations and government entities.​​

References

Adstiladrin Prescribing Information. Ferring Pharmaceuticals, Parsippany, NJ. Revised August 2024​.

American Cancer Society. Key Statistics for Bladder Cancer. Updated January 12, 2022. https://www.cancer.org/cancer/bladdercancer/about/key-statistics.html. Accessed August 20, 2024.

American Hospital Formulary Service (AHFS). Nadofaragene Firadenovec-vncg (Adstiladrin®). AHFS Drug Information 2024. [LexiComp Web site]. 03/11/2024. Available at: https://online.lexi.com/lco/action/home# [via subscription only]. Accessed August 20, 2024.

Balar AV, Kamat AM, Kulkarni GS, et al. Pembrolizumab monotherapy for the treatment of high-risk non-muscle invasive bladder cancer unresponsive to BCG (KEYNOTE-057): an open-label, single-arm, multicentre, phase 2 study. Lancet Oncol. 2021;22(7):919-930. 

Black P, Kassouf W. Management of recurrent or persistent non-muscle invasive bladder cancer. UpToDate. Updated December 2023. Accessed August 20, 2024. https://www.uptodate.com/contents/treatment-of-recurrent-or-persistent-non-muscle-invasive-urothelial-carcinoma-of-the-bladder​.

Boorjian SA, Alemozaffar M, Konety BR, et al. Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial. Lancet Oncol. 2021;22:107-117. 

Burger M, Catto JW, Dalbagni G, et al. Epidemiology and risk factors of urothelial bladder cancer. Eur Urol. 2013;63(2):234-241. 

Elsevier's Clinical Pharmacology. Nadofaragene Firadenovec-vncg (Adstiladrin®). [MD Consult Web site]. 07/24/2024. Available at: https://www.clinicalkey.com/#!/ [via subscription only]. Accessed August 20, 2024.

Ferring receives approval from U.S. FDA for Adstiladrin for high-risk, BCG-unresponsive non-muscle invasive bladder cancer. Ferring Pharmaceuticals. December 16, 2022. https://www.ferring.com/ferring-receives-approval-from-u-s-fda-for-adstiladrin-for-high-risk-bcg-unresponsive-non-muscle-invasive-bladder-cancer/. Accessed August 20, 2024.

Maroof H, Paramore L, Ali A. Theories behind Bacillus Calmette-Guérin failure in high-risk non-muscle-invasive bladder cancer and update on current management. Cancer Pathog Ther. 2024;2(2):74-80. ​

Kulkarni GS. Nadofaragene firadenovec: a new gold standard for BCG-unresponsive bladder cancer? [published correction appears in Lancet Oncol. 2021;22(1):e5]. Lancet Oncol. 2021;22(1):8-9.

Lexi-Drugs Compendium. Nadofaragene Firadenovec-vncg (Adstiladrin®). [Lexicomp Online Web site]. 07/30/2024. Available at: https://online.lexi.com/lco/action/home# [via subscription only]. Accessed August 20, 2024.

Micromedex® Healthcare Series [Internet database]. Nadofaragene Firadenovec-vncg (Adstiladrin®). Greenwood Village, CO: Thomson Micromedex. 03/14/2024. Available at: https://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed August 20, 2024.​

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Bladder Cancer. V4.2024. [NCCN Web site]. 05/09/2024. Available at: https://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf. Accessed on August 20, 2024.

National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium®. Nadofaragene Firadenovec-vncg (Adstiladrin®). [NCCN Web site]. 2024. Available at: https://www.nccn.org/compendia-templates/compendia/drugs-and-biologics-compendia [via subscription only]. Accessed August 20, 2024.

National Cancer Institute SEER Program. Cancer stat facts: Common cancer sites. https://seer.cancer.gov/statfacts/html/common.html. Accessed August 20, 2024.

U.S. Food & Drug Administration. FDA approves first gene therapy for the treatment of high-risk, non-muscle-invasive bladder cancer. 8/2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-treatment-high-risk-non-muscle-invasive-bladder-cancer. Accessed August 20, 2024.

Coding

CPT Procedure Code Number(s)
N/A
ICD - 10 Procedure Code Number(s)
N/A
ICD - 10 Diagnosis Code Number(s)

C67.0 Malignant neoplasm of trigone of bladder

C67.1 Malignant neoplasm of dome of bladder

C67.2 Malignant neoplasm of lateral wall of bladder

C67.3 Malignant neoplasm of anterior wall of bladder

C67.4 Malignant neoplasm of posterior wall of bladder

C67.5 Malignant neoplasm of bladder neck

C67.6 Malignant neoplasm of ureteric orifice

C67.7 Malignant neoplasm of urachus

C67.8 Malignant neoplasm of overlapping sites of bladder

C67.9 Malignant neoplasm of bladder, unspecified

D09.0 Carcinoma in situ of bladder

HCPCS Level II Code Number(s)
J9029 Intravesical instillation nadofaragene firadenovec-vncg, per therapeutic dose​​
Revenue Code Number(s)
N/A

Coding and Billing Requirements

Policy History

Revisions From​ 08.02.11b:
09/03/2025
​This policy has been reviewed and reissued to communicate the Company's continuing position on nadofaragene firadenovec-vncg (Adstiladrin®)​​.
10/21/2024

This version of the policy will become effective 10/21/2024​.

​Criteria for high-risk, Bacillus Calmette-Guérin​ (BCG)---unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors​ have been added to this policy in accordance with the National Comprehensive Cancer Network (NCCN):
  • As initial management
  • As recurrent or persistent disease that is cytology-positive, imaging- and cystoscopy-negative and bladder-positive

Revisions From​ 08.02.11a:
04/01/2024

This version of the policy will become effective 04/01/2024.


The following HCPCS code narrative has been revised in this policy:

FROM: J9029 Injection, nadofaragene firadenovec-vncg, per therapeutic dose

TO: J9029 Intravesical instillation nadofaragene firadenovec-vncg, per therapeutic dose​


Revisions From 08.02.11:

09/11/2023

This new policy #08.02.11 has been issued to communicate the Company's policy position on Nadofaragene Firadenovec-vncg (Adstiladrin®)​.​​


10/21/2024
10/21/2024
9/3/2025
08.02.11
Medical Policy Bulletin
Commercial
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