Nadofaragene Firadenovec-vncg (Adstiladrin)

Number: 1024

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses nadofaragene firadenovec-vncg (Adstiladrin) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Note: Requires Precertification: 

Precertification of nadofaragene firadenovec-vncg (Adstiladrin) is required of all Aetna participating providers and members in applicable plan designs. For precertification of nadofaragene firadenovec-vncg (Adstiladrin), call (866) 752-7021 or fax (888) 267-3277. For Statement of Medical Necessity (SMN) precertification forms, see Specialty Pharmacy Precertification.  

1. Criteria for Initial Approval

   Bladder Cancer

   Aetna considers nadofaragene firadenovec-vncg (Adstiladrin) medically necessary for treatment of bladder cancer when all of the following criteria are met:

   1. The member has non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS); and
   2. The disease is high-risk; and
   3. The disease is Bacillus Calmette-Guerin (BCG)-unresponsive.

   Aetna considers all other indications as experimental and investigational.

2. Continuation of Therapy

   Aetna considers continuation of nadofaragene firadenovec-vncg (Adstiladrin) therapy medically necessary in members requesting reauthorization for an indication listed in Section I when there is no evidence of unacceptable toxicity or disease recurrence while on the current regimen.

Dosage and Administration

Nadofaragene firadenovec-vncg is supplied as Adstiladrin suspension for intravesical instillation in single-use vials. All vials have a nominal concentration of 3 x 10¹¹ viral particles (vp)/mL. Each vial of Adstiladrin contains an extractable volume of not less than 20 mL.

Bladder Cancer

The recommended dose of Adstiladrin is 75 mL at a concentration of 3 x 10¹¹ viral particles (vp)/mL by intravesical instillation once every three months into the bladder via a urinary catheter.

Refer to full prescribing information for Adstiladrin for preparation and handling instructions.

Source: Ferring Pharmaceuticals, 2022

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Other CPT codes related to the CPB:
50720	Bladder instillation of anticarcinogenic agent (including retention time)
90586	Bacillus Calmette-Guerin vaccine (BCG) for bladder cancer, live, for intravesical use
HCPCS codes covered if selection criteria are met:
J9029	Injection, nadofaragene firadenovec-vncg, per therapeutic dose
Other HCPCS codes related to the CPB:
J9030	BCG live intravesical instillation, 1 mg
ICD-10 codes covered if selection criteria are met:
D09.0	Carcinoma in situ of bladder [Non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS)]

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Background

U.S. Food and Drug Administration (FDA)-Approved Indications 

• Adstiladrin is indicated for the treatment of adult patients with high-risk Bacillus Calmette-Guerin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors.

Compendial Uses

• Non-muscle invasive bladder cancer

Nadofaragene firadenovec-vncg is available as Adstiladrin (Ferring Pharmaceuticals) and is a non-replicating adenoviral vector-based gene therapy for intravesical instillation. Adstiladrin is designed to deliver a copy of a gene encoding a human interferon-alfa 2b (IFNα2b) to the bladder urothelium. The delivery of Adstiladrin via intravesical instillation causes ensuing cell transduction and transient local expression of the IFNα2b protein with anticipated anti-tumor activity (Ferring Pharmaceuticals, 2022).

According to the prescribing information, Adstiladrin is contraindicated in patients with hypersensitivity to interferon alfa or any component of the product.

Per the prescribing information, Adstiladrin carries the following warnings and precautions:

• Delaying cystectomy could lead to the development of metastatic bladder cancer, which can be lethal.
• Risk of disseminated adenovirus infection: Persons who are immunocompromised or immunodeficient may be at risk for disseminated infection from Adstiladrin due to low levels of replication-competent adenovirus. Avoid Adstiladrin exposure to immunocompromised or immunodeficient individuals.

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

Refer to the full prescribing information for Adstiladrin for use in specific populations.

On December 16, 2022, the U.S. Food and Drug Administration (FDA) approved Adstiladrin (nadofaragene firadenovec-vncg) 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. The FDA approval was based on supporting data from a multicenter clinical study evaluating the safety and effectiveness of Adstiladrin for the treatment of patients with high-risk BCG-unresponsive NMIBC (FDA, 2022).

The safety and efficacy of Adstiladrin was evaluated in an open-label, multicenter, single-arm trial that included 157 patients with high-risk BCG-unresponsive NMIBC with CIS with or without papillary tumors following transurethral resection, of whom 98 were considered evaluable for response. Patients received a single intravesical 75 mL dose of Adstiladrin (3x10¹¹ viral particles per mL). Repeat dosing was given once every 3 months for up to 12 months (four doses) or until unacceptable toxicity or recurrent high-grade (HG) NMIBC. Patients without evidence of HG  recurrence were allowed to continue Adstiladrin treatment every 3 months. The primary efficacy endpoints 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. In total, 51% of enrolled patients treated with Adstiladrin achieved a CR. The median duration of response was 9.7 months. Additionally, 46% of responding patients maintained CR for at least1 year (FDA, 2022; Ferring Pharmaceuticals, 2022).

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References