Nogapendekin Alfa Inbakicept-pmln (Anktiva)

Number: 1059

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 nogapendekin alfa inbakicept-pmln (Anktiva) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Note: Requires Precertification: 

Precertification of nogapendekin alfa inbakicept-pmln (Anktiva) is required of all Aetna participating providers and members in applicable plan designs. For precertification of nogapendekin alfa inbakicept-pmln (Anktiva), 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 nogapendekin alfa inbakicept-pmln (Anktiva) 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) with or without papillary tumors; and
   2. The disease is Bacillus Calmette-Guerin (BCG)-unresponsive; and
   3. The requested medication will be used in combination with Bacillus Calmette-Guerin (BCG); and
   4. The member will receive maintenance doses at months 4, 7, 10, 13 and 19 after induction therapy.

   Aetna considers all other indications as experimental, investigational, or unproven.

2. Continuation of Therapy

   Aetna considers continuation of nogapendekin alfa inbakicept-pmln (Anktiva) therapy [for a total of 24 maintenance doses (37 months of treatment)] medically necessary in members requesting reauthorization for an indication listed in Section I when there is no evidence of unacceptable toxicity or disease recurrence or progression while on the current regimen.

Dosage and Administration

Nogapendekin alfa inbakicept-pmln is supplied as Anktiva 400 mcg/0.4 mL solution in single-dose vials for intravesical instillation after dilution.

Anktiva is for intravesical use only. Do not administer by subcutaneous or intravenous or intramuscular routes.

The recommended dosage for Anktiva for the treatment of BCG-unresponsive nonmuscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors is as follows:

• For induction: 400 mcg administered intravesically with BCG once a week for 6 weeks. A second induction course may be administered if complete response is not achieved at month 3.
• For maintenance: 400 mcg administered intravesically with BCG once a week for 3 weeks at months 4, 7, 10, 13 and 19. For patients with an ongoing complete response at month 25 and later, additional maintenance instillations with BCG may be administered once a week for 3 weeks at months 25, 31, and 37 for a maximum of 9 additional instillations.
• Instill intravesically only after dilution. Total time from vial puncture to the completion of the intravesical instillation should not exceed 2 hours.

The recommended duration of treatment is until disease persistence after second induction, disease recurrence or progression, unacceptable toxicity, or a maximum of 37 months.

Refer to the full prescribing information for Anktiva for preparation and administration instructions.

Source: AGC Biologics, 2024

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Other CPT codes related to the CPB:
51720	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:
J9028	Injection, nogapendekin alfa inbakicept-pmln, for intravesical use, 1 microgram
Other HCPCS codes related to the CPB:
J9030	BCG live intravesical instillation, 1 mg
ICD-10 codes covered if selection criteria are met:
C67.0 – C67.9	Malignant neoplasm of bladder
D09.0	Carcinoma in situ of bladder

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Background

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

• Anktiva is indicated with Bacillus Calmette-Guérin (BCG) for the treatment of adult patients with BCG-unresponsive nonmuscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors.

Nogapendekin alfa inbakicept-pmln is available as Anktiva (AGC Biologics) which is an an interleukin-15 (IL-15) receptor agonist. It is a soluble complex 
consisting of (a) nogapendekin alfa (a human IL-15N72D variant, 114 amino acids) bound to (b) inbakicept [a dimeric human IL-15Rα sushi domain (65 amino acids)/human IgG1 Fc fusion protein (232 amino acids)]. IL-15 signals through a heterotrimeric receptor that is composed of the common gamma chain (γc) subunit, the beta chain (βc) subunit, and the IL-15-specific alpha subunit, IL-15 receptor α. IL-15 is trans-presented by the IL-15 receptor α to the shared IL-2/IL-15 receptor (βc and γc) on the surface of CD4+ and CD8+ T cells and NK cells. Anktiva binds to its receptor and results in proliferation and activation of NK, CD8+, and memory T cells without proliferation of immuno-suppressive Treg cells. In vivo, intravesicular Anktiva alone or in combination with BCG has shown anti-tumor activity when compared to BCG alone, in a carcinogen-induced model of bladder cancer in immunocompetent rats (ACG Biologics, 2024).

Anktiva, according to the prescribing information, carries the following warning and precaution:

• Delaying cystectomy can lead to the development of metastatic bladder cancer, which can be lethal.

The Anktiva prescribing information notes that the most common ((≥15%) adverse reactions, including laboratory test abnormalities, are the following: increased creatinine, dysuria, hematuria, urinary frequency, micturition urgency, urinary tract infection, increased potassium, musculoskeletal pain, chills and pyrexia.

Additionally, the Anktiva prescribing information notes use in pregnancy as follows:

• Pregnancy: May cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception.

On April 22, 2024, the U.S. Food and Drug Administration approved nogapendekin alfa inbakicept-pmln (Anktiva) with Bacillus Calmette-Guérin (BCG) for adult patients with 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 the QUILT-3.032 study, a single-arm, multicenter trial evaluating the efficacy of Anktiva in 77 adults with BCG-unresponsive, high-risk, NMIBC with CIS with or without Ta/T1 papillary disease following transurethral resection (AGC Biologics, 2024; FDA, 2024).

Participants, in the QUILT-3.032 study, received Anktiva 400mcg by intravesical instillation with BCG weekly for 6 consecutive weeks during the induction treatment period and then once a week every 3 weeks at 4, 7, 10, 13, and 19 months for participants with no or low grade disease. Participants with persistent CIS or high grade Ta disease at 3 months were eligible to receive a second induction course. Participants with ongoing complete response (CR) at 25 months were eligible to receive additional instillations once a week every 3 weeks at months 25, 31, and 37. The investigators assessed tumor status with cystoscopy and urine cytology every 3 months for up to 2 years and biopsy (random or cystoscopy-directed) was required within the first 6 months after treatment initiation. Ongoing response assessment beyond month 24 was performed per local community standards (AGC Biologics, 2024; FDA, 2024).

The major efficacy outcome measures were CR at any time and duration of complete response(DOR). CR was determined by a negative cystoscopy (with transurethral resection of bladder tumor [TURBT]/biopsies as applicable) and urine cytology (AGC Biologics, 2024; FDA, 2024). 

The CR rate was 62% (95% confidence interval [CI]: 51, 73). Fifty-eight percent of patients with CR had a DOR ≥ 12months and 40% had a DOR ≥ 24 months.

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References