Aetna Commercial Clinical Policy

Aetna Nadofaragene Firadenovec-vncg (Adstiladrin) Form

Effective Date

03/28/2023

Last Reviewed

08/23/2023

Original Document

  Reference



Background for this Policy

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.

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 (3x10

    11

    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).

    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 (commercial), or fax (888) 267-3277. For Statement of Medical Necessity (SMN) precertification forms, see

    Specialty Pharmacy Precertification .

    For Medicare Part B plans, call (866) 503-0857, or fax (844) 268-7263.

    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:

  • The member has non-muscle invasive bladder cancer;
    • and
  • The disease is high-risk;
    • and
  • The disease is Bacillus Calmette-Guerin (BCG)-unresponsive.

    • Aetna considers all other indications as experimental and investigational.

    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 10

    11

    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 10

    11

    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