A Regulatory Crossroads: ImmunityBio’s Fight for FDA Approval and the High Stakes for Patients and Investors

The biotech sector is rarely short on drama, but few stories in recent months have captured the tension between science, regulation, and patient need as starkly as ImmunityBio’s (NASDAQ: IBRX) clash with the FDA over its bladder cancer therapy, ANKTIVA. On May 2, 2025, the agency issued a Refusal to File (RTF) letter for the company’s supplemental Biologics License Application (sBLA) for ANKTIVA in combination with Bacillus Calmette-Guérin (BCG) for BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with papillary disease without carcinoma in situ (CIS)—a decision that directly contradicts its own January 2025 guidance. The stakes are high: for patients facing radical cystectomy, the therapy offers a potential lifeline; for investors, the outcome could redefine ImmunityBio’s valuation.

The Regulatory Whiplash: From Encouragement to Rejection

In January 2025, immunitybio received unanimous encouragement from FDA leadership—including representatives from the Center for Biologics Evaluation and Research (CBER), the Center for Drug Evaluation and Research (CDER), and the Office of Clinical Policy—to submit the sBLA for ANKTIVA+BCG in the papillary NMIBC indication. The FDA’s rationale was clear: the QUILT-3.032 trial data demonstrated 99% disease-specific survival at 12 months, 96% at 36 months, and 82% avoidance of bladder removal (cystectomy) in the papillary cohort—a population with limited treatment options and a high risk of mortality.

But by May 2, that guidance had vanished. The FDA’s RTF letter left ImmunityBio “shocked” and its advisors, including former FDA Principal Deputy Commissioner Dr. Rachel Sherman, questioning the agency’s logic. “This decision is rife with regulatory inaccuracies,” Sherman stated, emphasizing the trial’s rigor and the lack of alternatives for these patients.

The Clinical Data: A Case of “Same Trial, Different Standards”?

The crux of the controversy lies in the FDA’s inconsistency. ANKTIVA+BCG was already approved in 2024 for NMIBC with CIS, based on the same QUILT-3.032 trial. Both cohorts (CIS with papillary tumors vs. papillary without CIS) shared identical protocols, patient populations (BCG-unresponsive NMIBC), and endpoints like disease-specific survival and bladder preservation.

The papillary cohort’s data, while slightly less robust than the CIS cohort’s complete response rate (55% vs. 62% at 12 months), still showed durable outcomes, including a 93% avoidance of cystectomy at a median follow-up of 20.7 months. These results were hailed as “best in class” at the 2025 American Urological Association meeting, where experts highlighted ANKTIVA’s potential to spare bladders and extend survival.

What’s at Risk for ImmunityBio?

The RTF decision has immediate and long-term implications:
1. Clinical Impact: Patients with BCG-unresponsive papillary NMIBC (without CIS) face a 6–10 times larger population than CIS patients, yet the RTF leaves them without an approved therapy.
2. Financial Pressure: ANKTIVA’s sales surged 150% in Q1 2025 compared to Q4 2024, with net revenue hitting $16.5 million. Expanding the label to papillary NMIBC could unlock a broader market.
3. Regulatory Credibility: The FDA’s abrupt reversal raises concerns about its consistency in evaluating single-arm trials for life-threatening conditions—a precedent that could deter innovation in oncology.

The Path Forward: Urgency and Uncertainty

ImmunityBio has wasted no time pushing for resolution. It has requested a Type A meeting (expedited for major regulatory issues) and an FDA Advisory Committee review to independently assess the data. Dr. Patrick Soon-Shiong, the company’s founder, has framed the RTF as not just a regulatory snafu but a moral failure: “Delaying approval for this indication places thousands of patients at risk of life-altering surgery or death.”

Broader Implications: A Bellwether for Regulatory Policy

This case underscores a growing tension in drug development: How does the FDA balance expedited approval for unmet needs with rigorous evidence requirements? ANKTIVA’s prior approval for CIS relied on the same single-arm trial design that the agency now questions for the papillary indication—a contradiction that could embolden critics of the FDA’s flexibility.

For investors, the path forward hinges on three factors:
1. FDA’s Reasoning: Will the RTF letter’s objections—still undisclosed—be resolved through a Type A meeting, or will ImmunityBio need to resubmit with additional data?
2. Advisory Committee Input: An independent panel could provide clarity on whether the papillary cohort’s data meets regulatory thresholds.
3. Market Dynamics: With no competing therapies for BCG-unresponsive NMIBC, ANKTIVA’s bladder-preservation profile may force the FDA’s hand.

Conclusion: A Litmus Test for Innovation

ImmunityBio’s struggle is more than a regulatory hiccup—it’s a litmus test for how the FDA treats therapies addressing high-risk, underserved populations. The papillary NMIBC indication represents a large, desperate patient group with no alternatives to cystectomy. ANKTIVA’s data, while not perfect, aligns with the FDA’s 2024 approval logic for the CIS indication.

If the FDA relents, ImmunityBio’s stock (IBRX) could rebound, leveraging its 150% QoQ sales growth and the therapy’s clinical profile. If not, the company faces a reckoning—not just with investors but with the broader oncology community, which may question the FDA’s willingness to prioritize patient survival over rigid protocols.

The stakes couldn’t be clearer: For patients, it’s the difference between a bladder and a coffin. For investors, it’s the difference between a breakthrough and a bust.

Disclosure: This article is for informational purposes only and does not constitute investment advice.