| Drug Name |
ANKTIVA® - formerly N-803 (nogapendekin alfa inbakicept-pmln) |
| Active Ingredient |
nogapendekin alfa inbakicept-pmln |
| Date of Approval |
04/22/24 |
| Manufacturer |
ALTOR BIOSCIENCE, LLC, AN INDIRECT WHOLLY-OWNED SU |
| Approval Pathways and Indications |
Indication: ANKTIVA® is an interleukin-15 (IL-15) receptor agonist indicated for the treatment of adult patients with Bacillus Calmette-Guérin (BCG)-unresponsive nonmuscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors.
Approval Pathway: BLA |
| Therapeutic Class |
Antineoplastic Agent, Biological Response Modulator; Biological Response Modulator; Interleukin-15 (IL-15) Receptor Agonist |
| Formulation |
Solution for intravesical instillation |
| MoA |
Nogapendekin alfa inbakicept-pmln is an IL-15 receptor agonist. 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.
Binding of nogapendekin alfa inbakicept-pmln to its receptor results in proliferation and activation of NK, CD8+, and memory T cells without proliferation of immuno-suppressive Treg cells. In vivo, intravesicular nogapendekin alfa inbakicept-pmln alone or in combination with BCG showed anti-tumor activity when compared to BCG alone, in a carcinogen-induced model of bladder cancer in immunocompetent rats. |
| Dosing and Administration |
400 mcg/0.4 mL, clear to slightly opalescent and colorless to slightly yellow solution in single-dose vials for intravesical instillation after dilution.
• For induction: 400 mcg administered intravesically with BCG once a week for 6 weeks. A second induction course may be administered if complete response (CR) 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 CR 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.
• Instill intravesically only after dilution. Total time from vial puncture to the completion of the intravesical instillation should not exceed 2 hours. |
| Administered by self or by HCP |
Administered by HCP |
| Place in Therapy |
Bladder cancer ranks as the 10th most commonly diagnosed cancer worldwide, with the American Cancer Society predicting 83,190 new cases and 16,840 deaths from it in the U.S. in 2024. Approximately 80% of cases are NMIBC, confined to the bladder's inner wall layer upon diagnosis. The standard treatment involves intravesical instillation of BCG, a benign bacteria inducing an immune response near cancer cells, clearing cancer in many patients. However, BCG fails in 30-40% of cases, and in around 50% of responders, cancer recurs. ANKTIVA®, in combination with BCG, offers NMIBC patients a non-invasive therapeutic alternative, with FDA approval based on safety and efficacy outcomes, including CR rates and response duration. ANKTIVA®, a first-in-class IL-15 agonist immunotherapy, activates NK cells, CD8+ killer T cells, and CD4+ T helper cells, promoting memory killer T cell proliferation. This mechanism, akin to dendritic cell biology, marks a step forward in immunotherapy beyond T cells, yielding durable CRs. |
| Expected Market Launch Date |
Availability is anticipated May 2024. |
| New Molecular Entity (NME) or Existing Formulation |
NME |
| Expected Cost |
Unavailable |
| Product Discontinuation |
N/A |
| Clinical Trials |
The efficacy of ANKTIVA® was evaluated in QUILT-3.032 (NCT03022825), a single-arm, multicenter trial in 77 adults with BCG-unresponsive, high-risk, NMIBC with 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 5 of 6 doses of an initial induction course plus either of at least 2 of 3 doses of maintenance therapy or at least 2 of 6 doses of a second induction course. Prior to treatment, all patients with Ta or T1 disease had undergone transurethral resection of bladder tumor (TURBT) to remove all resectable disease.
Patients received 400 mcg ANKTIVA® 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 patients with no or low-grade disease. Patients with persistent CIS or high-grade Ta disease at 3 months were eligible to receive a second induction course. Patients 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 CR at any time (as defined by negative results for cystoscopy [with TURBT/biopsies as applicable] and urine cytology) and duration of response which was achieved in 62% of participants. |
| Sources |
Jhollister. (2024, April 25). ImmunityBio announces FDA approval of Anktiva®, first-in-class IL-15 receptor agonist for BCG-unresponsive non-muscle invasive bladder cancer. ImmunityBio. https://immunitybio.com/immunitybio-announces-fda-approval-of-anktiva-first-in-class-il-15-receptor-agonist-for-bcg-unresponsive-non-muscle-invasive-bladder-cancer/ |