ImmunityBio Announces FDA Acceptance of Biologics License Application for N-803 in BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer Carcinoma In Situ
This acceptance represents the first regulatory filing for N-803, an IL-15 superagonist, which was granted Breakthrough Therapy and Fast Track designations in combination with Bacillus Calmette-Guérin (BCG) from the
U.S. Food and Drug Administration(FDA) for this indication with a target PDUFA date of May 23, 2023
- The BLA submission is based on the positive QUILT 3.032 trial results in which 71% of BCG-unresponsive NMIBC patients who had failed on previous therapies showed a complete response with a median duration of 26.6 months; cystectomy avoidance rate of 91% and 100% bladder cancer overall survival at 24 months with zero serious adverse events (SAE)
This combination of N-803 with BCG is ImmunityBio’s first BLA to reach this stage of FDA acceptance for review. This marks an important milestone in the pursuit of ImmunityBio’s vision of transforming how cancer patients are treated without high-dose chemotherapy, but instead by activating the patient’s innate immune system. If approved, N-803 plus BCG would be the first immunotherapy combination for this indication in 23 years that can be delivered directly to the bladder (intravesically) to induce natural killer cells and T cells. It represents an essential step in the clinical demonstration of the Nant Cancer Vaccine hypothesis proposed by ImmunityBio’s founder,
N-803 has a unique mechanism of action that leads to the proliferation of NK and T cells that are cells of the adaptive and innate immune system. Through this action, N-803 provides a secondary boost to the immunological response generated by BCG for bladder cancer, or by a checkpoint inhibitor for other indications. In the QUILT 3.032 study, 71% of patients who had failed on previous therapies showed an over 50% increase in both response and median duration compared to the FDA-approved alternatives Valrubicin and Pembrolizumab, a systemic checkpoint inhibitor therapy for this indication.
“This BLA acceptance brings us a very important step closer to being able to offer this promising combination therapeutic to more people living with NMIBC and, ultimately, reduce the incidence of cystectomies,” said
“We are pleased the FDA has begun its review, and
The BLA submission is supported by the results from ImmunityBio’s bladder cancer trials including QUILT 3.032, an open-label, three cohort, multicenter Phase 2/3 study of intravesical BCG plus N-803 in patients with BCG-unresponsive high-grade NMIBC (NCT03022825) that was opened in 2017. The primary endpoint for Cohort A of this Phase 2/3 study is incidence of complete response (CR) of CIS at any time. Results of this trial were presented at the 2022
ImmunityBio’s IL-15 superagonist N-803
The cytokine interleukin-15 (IL-15) plays a crucial role in the immune system by affecting the development, maintenance, and function of the natural killer (NK) and T cells. N-803 is a novel IL-15 superagonist complex consisting of an IL-15 mutant (IL-15N72D) bound to an IL-15 receptor α/IgG1 Fc fusion protein. Its mechanism of action is direct specific stimulation of CD8+ T cells and NK cells through beta gamma T-cell receptor binding (not alpha) while avoiding T-reg stimulation. N-803 has improved pharmacokinetic properties, longer persistence in lymphoid tissues and enhanced anti-tumor activity compared to native, non-complexed IL-15 in vivo.
N-803 has been studied in more than 700 patients in multiple Phase 1 and 2 trials in both liquid and solid tumors. It is currently being studied in trials for non-muscle-invasive bladder cancer, pancreatic cancer, non-small-cell lung cancer, non-Hodgkin’s lymphoma, and HIV.
N-803 has received both Breakthrough Therapy and Fast Track designations by the FDA for the treatment of BCG-unresponsive NMIBC CIS, as well as Fast Track designation for BCG-unresponsive NMIBC papillary and BCG-naïve NMIBC CIS. However, it is important to note such designations may not lead to a faster development process or regulatory review and may not increase the likelihood that a product candidate will receive approval. Seminal patents covering intravesical administration of BCG and N-803 were issued (US 11,173,191 B2 and US 9,925,247 B2) providing term coverage until 2035.
ImmunityBio’s clinical pipeline consists of 27 clinical trials—18 of which are in Phase 2 or 3 development—across 13 indications in liquid and solid tumors (including bladder, pancreatic, and lung cancers) and infectious diseases (including SARS-CoV-2 and HIV). N-803 (Anktiva™), ImmunityBio’s lead cytokine fusion protein, is a novel interleukin-15 (IL-15) superagonist complex and has received Breakthrough Therapy and Fast Track Designations from the
The company has established GMP manufacturing capacity at scale with cutting-edge cell manufacturing expertise and ready-to-scale facilities, as well as extensive and seasoned R&D, clinical trial, and regulatory operations, and development teams. For more information, please visit: www.immunitybio.com
Forward Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, such as statements regarding data from the clinical trials for certain of ImmunityBio’s product candidates, the regulatory review process and timing thereof, potential implications to be drawn from the QUILT 3.032 and other studies, whether the described mechanism of action contributes to response rate and duration, potential commercialization of ImmunityBio’s product candidates, ImmunityBio’s product candidates as compared to existing treatment options, and clinical trial advancements and data, among others. Statements in this press release that are not statements of historical fact are considered forward-looking statements, which are usually identified by the use of words such as “anticipates,” “believes,” “continues,” “could,” “estimates,” “expects,” “intends,” “may,” “plans,” “potential,” “predicts,” “indicate,” “projects,” “seeks,” “should,” “will,” and variations of such words or similar expressions. Statements of past performance, efforts, or results of our preclinical and clinical trials, about which inferences or assumptions may be made, can also be forward-looking statements and are not indicative of future performance or results. Forward-looking statements are neither forecasts, promises nor guarantees, and are based on the current beliefs of ImmunityBio’s management as well as assumptions made by and information currently available to
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