Coverage Policy Manual - Arkansas Blue Cross and Blue Shield

Nogapendekin alfa inbakicept-pmln (e.g., Anktiva)

Description:

Nogapendekin alfa (e.g., Anktiva) is a human interleukin (IL)-15N72D variant that is bound to inbakicept, a dimeric human IL-15R alpha sushi domain/human IgG1 Fc fusion protein and the complex acts as an IL-15 receptor super-agonist. IL-15 then signals through a heterotrimeric receptor that is composed of the common gamma chain subunit, the beta chain subunit, and the alpha subunit (specific to IL-15). IL-15 is trans-presented by the IL-15 receptor alpha to the shared IL-2/IL-15 receptors (beta chain and gamma chain) on the surface of CD4 and CD8 T-cells and NK cells. Binding of these receptors results in proliferation and activation of NK, CD8, and memory T cells without proliferation of immunosuppressive regulatory T-cells.

Regulatory Status

Nogapendekin alfa inbakicept-pmln (e.g., Anktiva) was approved by the U.S. Food and Drug Administration (FDA) on April 22, 2024, for the treatment of individuals with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), with or without papillary tumors in combination with Bacillus Calmette-Guérin (BCG).

Coding

See CPT/HCPCS Code section below.

Policy/
Coverage:

Prior Approval is required for Nogapendekin alfa inbakicept-pmln (e.g., Anktiva).

The initial use of this drug requires documentation of direct physician involvement (MD/DO) in the ordering and evaluation, as well as signature, in the medical records submitted for prior approval. Concurrent review will require continued evidence of appropriate physician involvement.

For members of plans that utilize an oncology benefits management program, Prior Approval is required for this service when rendered for oncologic indications and is managed through the oncology benefits management program.

Approval timeframes may differ for members/participants of Self-Insured plans.

Effective November 7, 2024

Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria

Nogapendekin alfa inbakicept-pmln (e.g., Anktiva) meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when ALL the following criteria are met:

INITIAL APPROVAL STANDARD REVIEW for up to 12 months:

1. Individual is 18 years of age or older (Anktiva, 2024); AND

2. Individual has a diagnosis of nonmuscle invasive bladder cancer (NMIBC) (Anktiva, 2024); AND

3. Individual has ECOG performance status of 2 or lower; AND

4. Individual has Bacillus Calmette-Guerin (BCG) unresponsive disease (see policy guidelines); AND

5. Individual has carcinoma in situ (CIS) with papillary tumors (Anktiva, 2024); OR

6. Individual has carcinoma in situ (CIS) without papillary tumors (Anktiva, 2024); OR

7. Individual will be using nogapendekin alfa inbakicept (e.g., Anktiva) as initial management or for cytology-positive, imaging and cystoscopy-negative, bladder positive recurrent or persistent disease (NCCN 2A); AND

8. Nogapendekin alfa inbakicept (e.g., Anktiva) will be given in combination with BCG (Anktiva, 2024); AND

9. Must be dosed in accordance with the FDA label unless otherwise specified.

CONTINUED APPROVAL for up to 12 months:

1. Individual has met initial approval criteria and completed a full induction protocol; AND

2. Individual achieved a complete response at month 3 and maintenance therapy is indicated in opinion of oncologist leading the case; OR

3. Individual did not achieve complete response at month 3 and reinduction therapy is indicated in in opinion of oncologist leading the case; AND

4. Total duration of therapy with nogapendekin alfa inbakicept (e.g., Anktiva) does not exceed 37 months (Anktiva, 2024); AND

5. Must be dosed in accordance with the FDA label.

Policy guidelines

BCG unresponsive disease is defined as persistent or recurrent CIS alone or with Ta/T1 disease within 12 months of completion of adequate BCG therapy. Adequate BCG therapy is defined as administration of at least five of six doses of an initial induction course plus either of at least two of three doses of maintenance therapy or at least two of six doses of a second induction course.

The ECOG or Eastern Cooperative Oncology Group Performance Status is based on the following scale:

0 = Fully active, able to carry on all pre-disease performance without restriction
1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, for example, light housework, office work
2 = Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours
3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours
4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair
5 = Dead

Off-label

The use of this drug is covered if an FDA-approved oncologic indication exists (not listed as an indication above) with the member meeting all the additional requirements of the prescribing information (package insert listed in the “Indications and Usage”) AND/OR a NCCN category 1 or 2A recommendation is recognized in the NCCN Drugs and Biologics Compendium with the member meeting specified criteria (See policy #2000030).

Dosage and Administration

Dosing per FDA Guidelines where applicable. For off-label indications, authorizations will not exceed 400 mcg once weekly in a 6-week course (may be repeated) OR maximum recommended doses as outlined in dosage and administration section unless medical literature supports a higher dose.

The recommended dose of nogapendekin alfa inbakicept-pmln (e.g., Anktiva) is 400 mcg intravesically weekly for 6 weeks as induction in combination with BCG (50 mg per instillation). A second induction course may be administered if complete response is not achieved at month 3.

Nogapendekin alfa inbakicept-pmln (e.g., Anktiva) is available as a 400 mcg/0.4 mL solution for intravesical instillation.

Nogapendekin alfa inbakicept-pmln (e.g., Anktiva) should be administered as an intravesical instillation by a healthcare professional.

Please refer to separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria

Nogapendekin alfa inbakicept-pmln (e.g., Anktiva), for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.

For members with contracts without primary coverage criteria, nogapendekin alfa inbakicept-pmln (e.g., Anktiva), for any indication or circumstance not described above, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.

Rationale:

Nogapendekin alfa was evaluated in QUILT-3.032 (NCT03022825), a Phase 2/3 single-arm, multicenter trial that included 77 efficacy-evaluable adults with BCG-unresponsive, high-risk NMIBC CIS with or without Ta/T1 papillary disease following transurethral resection.

BCG-unresponsive, high-risk NMIBC CIS was defined as persistent or recurrent CIS alone or with Ta/T1 disease within 12 months of completion of adequate BCG therapy. Adequate BCG therapy was defined as administration of at least five of six doses of an initial induction course plus either of at least two of three doses of maintenance therapy or at least two of six doses of a second induction course. Prior to treatment, all individuals with Ta or T1 disease had undergone TURBT to remove all resectable disease. Residual CIS not amenable to complete resection, fulguration, or cauterization was

permitted. The trial excluded individuals with history of or evidence of muscle invasive (i.e., T2, T3, T4), locally advanced, metastatic, and/or extra-vesical (i.e., urethra, ureter, or renal pelvis) bladder cancer.

Individuals received 400 mcg NOGAPENDEKIN ALFA 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 individuals with no or low-grade disease. Individuals with persistent CIS or high-grade Ta disease at 3 months were eligible to receive a second induction course. Individuals with ongoing CR at 25 months were eligible to receive additional instillations once a week every 3 weeks at months 25, 31, and 37. Assessment of tumor status was performed every 3 months for up to two years. Assessment for ongoing response beyond month 24 was per local community standards. Random or cystoscopy directed biopsies were required within the first 6 months after treatment initiation. The major efficacy outcome measures 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. The median age of individuals was 73 years (range, 50–91 years); 86% were male; race was White (90%), Black (6%), Asian (1%), American Indian or Alaska Native (1%), or Unknown (1%); and individuals had baseline ECOG performance status of 0 (83%) or 1 (17%).

Tumor characteristics at study entry were CIS without Ta/T1 papillary disease (69%), CIS with Ta papillary disease (21%) or CIS with T1 +/- Ta papillary disease (10%). Baseline high-risk NMIBC disease status was 43% refractory and 57% relapsed. The median number of prior BCG doses received was 12 doses (range: 8–45 doses); 13% received partial-dose prior BCG. Baseline cystoscopy imaging modality was white light (57%), blue light or narrow band imaging (40%), and unknown (3%).

The safety of nogapendekin alfa with BCG was evaluated in Cohort A (n = 88) of QUILT-3.032. The median number of doses of nogapendekin alfa with BCG administered to individuals was 12 (range: 2 to 30) doses. The median duration of exposure to nogapendekin alfa with BCG was 7.1 months (range: 0.26 to 36.3 months). Serious adverse reactions occurred in 16% of individuals receiving Nogapendekin alfa with BCG, with hematuria as the most common reaction, at 3.4%. A fatal adverse reaction of cardiac arrest occurred in 1.1% of individuals (1 individual) receiving nogapendekin alfa with BCG. Permanent discontinuation of Nogapendekin alfa with BCG due to adverse reactions was observed in 7% of individuals. The primary adverse reaction leading to permanent discontinuation was musculoskeletal pain, affecting 2.3% of individuals. Dosage interruptions due to adverse reactions affected 34% of individuals receiving Nogapendekin alfa with BCG. Common adverse reactions leading to dosage interruption included urinary tract infection (10%), dysuria (8%), hematuria (6%), and bladder irritation (6%). Dosage reductions were not permitted for Nogapendekin alfa, but dose reduction of BCG was allowed for adverse reactions and occurred in 3.4% of individuals. The adverse reactions leading to BCG dose reduction included urinary tract infection (2.3%), hematuria (1.1%), urinary frequency (1.1%), and bladder irritation (1.1%). The most common (≥15%) adverse reactions, including laboratory test abnormalities, were increased creatinine, dysuria, hematuria, urinary frequency, micturition urgency, urinary tract infection, increased potassium, musculoskeletal pain, chills, and pyrexia.

CPT/HCPCS:

References:

Anktiva(2024) Package Insert Bothell, WA; Altor BioScience, LLC, 2024.

Chamie, Karim et al.(2023) IL-15 Superagonist NAI in BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer. NEJM evidence vol. 2,1 (2023): EVIDoa2200167. doi:10.1056/EVIDoa2200167

Kamat AM, et al.(2016) Definitions, end points, and clinical trial designs for non-muscle-invasive bladder cancer. Recommendations from the International Bladder Cancer Group. J Clin Oncol. 2016;34(16):1935-44. doi:10.1200/JCO.2015.64.4070

NCCN(2024) Drugs & Biologics Compendium for Nogapendekin alfa inbakicept-pmln (Anktiva). Accessed September 26, 2024. online to NCCN.org.

Pijpers OM, Boormans JL.(2024) Disease progression in Bacillus Calmette Guerin unresponsive non-muscle invasive bladder cancer individuals with carcinoma in situ, participating in clinical trials on bladder-sparing treatment. Translational Andrology and Urology. 2024 Mar 3;13(3):479.

Suderman J, et al.(2023) Re: IL-15 Superagonist NAI in BCG Unresponsive non-muscle-invasive bladder cancer. Eur Urol. 2023;83(6):581. doi:10.1016/j.eururo. 2023.01.00

Waheed A, Gul MH, Wardak AB, Raja HA, Hussaini H.(2024) Nogapendekin alfa inbakicept-PMLN: first approval milestone for bcg-unresponsive non-invasive bladder cancer, editorial. Annals of Medicine and Surgery.:10-97.

Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants.