ImmunityBio's Regulatory Crossroads: Can ANKTIVA Overcome the FDA's Inconsistency?

ImmunityBio (NASDAQ: IBRX) finds itself in a high-stakes regulatory battle after the FDA’s abrupt reversal on its supplemental Biologics License Application (sBLA) for ANKTIVA in BCG-unresponsive non-muscle invasive bladder cancer (NMIBC). Despite receiving explicit encouragement to submit the application in January 2025, the FDA issued a Refusal to File (RTF) letter on May 2 for the papillary disease indication—a decision the company calls “incomprehensible.” This article explores the regulatory clash, clinical data, and market implications, while questioning whether ANKTIVA can still deliver on its promise.

The Regulatory Whiplash: From Green Light to Red Flag

In January 2025, FDA leaders from CBER, CDER, and OCE held an in-person meeting with immunitybio, unanimously urging the company to submit the sBLA for ANKTIVA+BCG in BCG-unresponsive NMIBC with papillary disease (without carcinoma in situ, or CIS). The Agency’s rationale? The trial data from the QUILT-3.032 study demonstrated life-saving outcomes for a population at risk of cystectomy or metastasis. Relying on this guidance, ImmunityBio filed the application in March.

Yet on May 2, the FDA refused to file the sBLA for the papillary indication, despite approving the same trial’s data for CIS with papillary tumors in 2024. The inconsistency has sparked outrage:
- Dr. Patrick Soon-Shiong, ImmunityBio’s CEO, called the RTF a “confounding inconsistency,” noting that both cohorts shared the same trial design, treatment protocols, and safety profiles.
- Dr. Rachel Sherman, former FDA Principal Deputy Commissioner, condemned the RTF as “rife with regulatory inaccuracies,” emphasizing the lack of alternatives for patients with BCG-unresponsive papillary NMIBC.

Clinical Data: A Case for Urgency

The sBLA was built on Cohort B of the QUILT-3.032 trial, a Phase II/III single-arm study involving 80 patients with BCG-unresponsive high-grade papillary NMIBC:
- Disease-specific survival: 99% at 12 months, 96% at 36 months.
- Bladder preservation: 82% avoided cystectomy at 36 months, with some patients remaining cystectomy-free for over a decade.
- Disease-free survival (DFS): 55% at 12 months, 51% at 18 months, and 48% at 24 months.

These outcomes are critical for a patient population with few options: BCG-unresponsive NMIBC has a 30–50% risk of progressing to muscle-invasive bladder cancer within three years, with a 50%+ 5-year mortality rate. ANKTIVA’s mechanism—activating NK cells and CD8+ T cells—offers a pathway to durable immune responses, as seen in the 10-year follow-up data.

Market Impact: Sales Growth vs. Regulatory Uncertainty

ImmunityBio’s Q1 2025 results highlight the commercial stakes:

- Q1 2025 ANKTIVA sales: $16.5 million, a 129% increase from Q4 2024 and 150% from the prior year.
- J-code implementation: The permanent J9028 billing code, secured in January 2025, has streamlined reimbursement, driving a 69% month-over-month sales surge in March.

However, the RTF’s uncertainty looms large. A delayed sBLA approval could stall revenue growth for the papillary indication, which represents a larger patient population than CIS (papillary NMIBC is 6–10 times more common).

The Path Forward: What’s at Stake?

ImmunityBio has requested a Type A meeting (expedited FDA consultation) and an Advisory Committee review to resolve the RTF. The company argues that:
1. Prior FDA precedent: Single-arm trials have been accepted for life-threatening conditions (e.g., HIV).
2. Clinical urgency: Patients lack alternatives, and the papillary indication aligns with the Agency’s priority for bladder preservation.
3. Data consistency: The trial’s durability and safety data mirror the CIS indication’s approval.

Analysts and investors are split:
- Bullish view: The FDA’s prior approval of Cohort A (CIS) suggests eventual approval for Cohort B, especially if ImmunityBio can clarify the RTF’s basis.
- Bearish view: Regulatory inconsistency could signal broader FDA skepticism toward single-arm oncology trials, or internal misalignment at the Agency.

Conclusion: Riding the Regulatory Wave

ImmunityBio’s fate hinges on its ability to reconcile the FDA’s January guidance with its May RTF. The clinical data for ANKTIVA+BCG in papillary NMIBC are compelling, but the Agency’s sudden shift raises red flags about regulatory rigor and consistency.

For investors, the stock’s performance will depend on two factors:
1. Resolution of the RTF: A Type A meeting or Advisory Committee review could salvage the sBLA, unlocking the papillary market and boosting sales.
2. Pipeline diversification: ANKTIVA’s Expanded Access Protocol for lymphopenia and its RMAT designation offer alternate growth avenues.

While Q1 sales growth is encouraging, the FDA’s inconsistency poses a near-term risk. However, if ImmunityBio can navigate this regulatory hurdle, ANKTIVA’s bladder preservation data and growing J-code-enabled sales could position it as a leader in NMIBC therapy.

Final word: The FDA’s decision to prioritize patient urgency over procedural nitpicks could be the difference between a regulatory setback and a breakthrough. Stay tuned.