ImmunityBio Requests Urgent FDA Meeting After Refusal to File sBLA for ANKTIVA in NMIBC Papillary Disease, Citing Sudden Reversal from January Guidance
ImmunityBio, Inc. (NASDAQ: IBRX), a clinical-stage immunotherapy company focused on developing therapies for difficult-to-treat cancers and infectious diseases, announced that it has received a Refusal to File (RTF) letter from the U.S. Food and Drug Administration (FDA) regarding its supplemental Biologics License Application (sBLA) for the use of ANKTIVA (N-803) in combination with Bacillus Calmette-Guerin (BCG) in patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) in the papillary disease setting.
This decision comes as a surprise to the company, especially in light of direct and unanimous guidance it received from FDA leadership earlier this year. According to ImmunityBio, the company was encouraged during a face-to-face meeting with the FDA in January 2025 to promptly submit the sBLA. The meeting reportedly included senior officials from multiple divisions, including the Center for Biologics Evaluation and Research (CBER), the Center for Drug Evaluation and Research (CDER), and the Oncology Center of Excellence (OCE). All parties present at the meeting confirmed that the data generated from ImmunityBio’s QUILT 3.032 clinical trial supported the submission of the application.
ImmunityBio proceeded with the submission in March 2025, relying on what it describes as “unambiguous guidance” from the agency. However, on May 2, 2025, the company received an unexpected RTF letter from the FDA, stating that the agency would not review the sBLA in its current form. This development has prompted ImmunityBio to urgently request a Type A meeting with the FDA to reconcile what it sees as a stark contradiction between the agency’s prior encouragement and its latest regulatory decision.
Background on ANKTIVA and the QUILT 3.032 Trial
ANKTIVA (N-803), an IL-15 superagonist fusion protein, was previously approved by the FDA in 2024 for use in combination with BCG for patients with BCG-unresponsive NMIBC with carcinoma in situ (CIS), including those with papillary tumors (referred to as Cohort A in the QUILT 3.032 trial). The supplemental application at the heart of the current dispute focuses on Cohort B of the same trial—patients with papillary disease without CIS.
The QUILT 3.032 trial evaluated the safety and efficacy of ANKTIVA plus BCG in both CIS and non-CIS patients with NMIBC who had previously failed BCG therapy. ImmunityBio emphasized that the same therapeutic regimen, surgical procedures, and follow-up protocols were used for both cohorts, making the FDA’s decision not to file the sBLA for papillary-only patients even more perplexing.
Long-term follow-up data from the trial were particularly compelling, according to the company. Patients in Cohort B demonstrated a disease-specific overall survival rate of 99% at 12 months and 96% at 36 months. Additionally, more than 82% of patients were able to avoid radical cystectomy—a major, life-altering surgery involving complete removal of the bladder. Some patients in earlier trials have reportedly remained cystectomy-free for over 10 years. ImmunityBio believes these outcomes represent the most durable data to date in this high-risk patient population.
Company Response and Urgent Call for FDA Dialogue
Dr. Patrick Soon-Shiong, Executive Chairman, Founder, and Global Chief Scientific and Medical Officer at ImmunityBio, expressed deep concern over the FDA’s reversal.
“Our commitment to NMIBC patients in the papillary indication and our belief in ANKTIVA’s potential remain unchanged,” said Dr. Soon-Shiong. “Despite receiving a refusal to file letter regarding our sBLA, we are determined to work with the FDA to address this inconsistency. We have already requested a Type A meeting and are open to an FDA Advisory Committee review as part of the process.”
Dr. Soon-Shiong emphasized that ANKTIVA+BCG was recently highlighted at the 2025 American Urological Association (AUA) meeting as a best-in-class treatment by leading urologic oncology experts. He reiterated the importance of providing these patients—who are at risk of disease progression and facing the traumatic prospect of radical bladder removal—with an effective and less invasive treatment option.
“Patients with BCG-unresponsive papillary disease are at risk of progressing from non-muscle invasive to muscle-invasive bladder cancer—a turning point associated with significantly higher morbidity and mortality,” he added. “Given the strong safety profile of ANKTIVA and the already-approved indication for patients with CIS, the refusal to even file this application is deeply troubling.”
Dr. Soon-Shiong also pointed out the scientific inconsistency of the FDA’s position. “It is confounding that the agency would approve this same drug, in the same trial, for one cohort but then refuse to even review its efficacy in another cohort within the same patient population. The surgical approach, dosing, and outcomes were nearly identical. The denial lacks regulatory and clinical justification.”
Support from Regulatory Experts
Dr. Rachel Sherman, former FDA Principal Deputy Commissioner and a regulatory veteran known for her work in developing expedited pathways during the HIV crisis, voiced similar concerns about the RTF decision. She personally attended the January 2025 meeting with ImmunityBio and FDA officials.
“I was stunned to learn that ImmunityBio had received a Refusal to File letter,” said Dr. Sherman. “In my opinion, the decision is fraught with regulatory inaccuracies. During the January meeting, there was clear consensus among all parties that a supplemental BLA should be submitted based on the compelling data from QUILT 3.032. These are high-risk patients with limited options—facing a disease that can escalate rapidly. Delaying access to potentially lifesaving therapies is unacceptable.”
Dr. Sherman further noted that the FDA’s rationale for the RTF—allegedly citing insufficient data—is difficult to reconcile with the agency’s prior approval of ANKTIVA+BCG for CIS patients based on the same trial.
“It is simply incomprehensible that the FDA would now argue that this study isn’t sufficient to support a review, when it already formed the basis of an approved treatment for another subset of NMIBC,” she said. “There is an urgent need to resolve this issue in the interest of patient health and scientific integrity.”
ImmunityBio has formally requested a Type A meeting, the highest priority meeting level granted by the FDA, typically reserved for addressing stalled development programs and regulatory disagreements. The company is also open to an FDA Advisory Committee meeting, where external experts and the public can weigh in on the matter.
In the meantime, ImmunityBio continues to advocate for patients with BCG-unresponsive NMIBC, emphasizing the long-term, bladder-sparing benefits of ANKTIVA+BCG therapy. The company has pledged to work with the FDA constructively to address any concerns raised in the RTF letter, but maintains that the current regulatory stance is inconsistent, scientifically flawed, and potentially harmful to patients in urgent need of treatment.
“We are committed to transparency, collaboration, and above all, patient care,” said Dr. Soon-Shiong. “This decision must be revisited—not just for the sake of regulatory consistency, but for the lives and quality of life of the patients we aim to serve.”
As the company awaits a formal meeting with the FDA, stakeholders across the healthcare and regulatory communities will be closely watching how this critical case unfolds—one that touches on science, policy, and above all, the well-being of patients living with one of the most challenging forms of bladder cancer.
