FDA Issues Refusal to File for ImmunityBio’s sBLA for Anktiva in BCG-Unresponsive NMIBC

Image Credit: Adobe Stock Images/Sebastian Kaulitzki

The FDA has issued a Refusal to File (RTF) letter to ImmunityBio for its supplemental biologics license application (sBLA) seeking to expand the use of Anktiva (nogapendekin alfa inbakicept-pmln) in combination with the Bacillus Calmette-Guérin (BCG) vaccine for patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with papillary disease.

According to ImmunityBio, the move by the FDA contradicts prior guidance from the agency during a January 2025 meeting, in which senior FDA officials encouraged submission of the sBLA based on data from the Phase II/III QUILT-3.032 study.¹

“Our commitment to NMIBC patients in the papillary indication and our belief in Anktiva’s potential based on the strength of the clinical response and long duration of five-year follow-up remains unchanged, despite our receipt of a refusal to file letter regarding our supplemental BLA,” said Patrick Soon-Shiong, founder, executive chairman, global chief scientific and medical officer, ImmunityBio, in the press release. “We are fully determined to work with the FDA as quickly as possible, including having already requested a Type A meeting, to explore the best path forward. We would also welcome an FDA Advisory Committee meeting as part of the regulatory process going forward.”

The open-label, single-arm, multicenter QUILT-3.032 study evaluated intravesical BCG plus Anktiva (Cohorts A and B) or Anktiva alone (Cohort C) in 190 patients with BCG-unresponsive, high-grade NMIBC. All patients received intravesical administration via urinary catheter over six weeks, followed by maintenance or re-induction at three months and ongoing treatment through 36 months. The primary endpoint for Cohort A (patients with carcinoma in situ [CIS] with or without papillary disease) was complete response (CR). For Cohort B (patients with papillary disease without CIS), the primary endpoint was the disease-free rate at 12 months.^1,2

In results announced in November 2024, Anktiva achieved a 71% CR rate with a durable response extending up to 54 months. ImmunityBio emphasized that the same study formed the basis for the FDA’s previous approval of Anktiva for patients with papillary disease and CIS in 2024.³

“We presented our data at the recent 2025 American Urological Association meeting, and Anktiva + BCG was considered best in class and best in disease by the thought leaders in attendance, when compared to all therapies currently approved or in development,” continued Soon-Shiong, in the press release. “Patients with BCG-unresponsive papillary disease face a life-changing and life-threatening prospect of a total radical cystectomy, as well as the danger of the disease progressing to muscle invasion, with consequent progression and mortality.”

The company also raised concerns about consistency in the FDA’s decision-making process. Soon-Shiong noted that the previously approved indication includes patients with papillary disease, yet the agency now claims that the data are insufficient to support filing for patients with papillary disease alone, even though both groups were included in QUILT-3.032.

ImmunityBio released a chart showing that patients in both Cohorts A and B received the same surgical procedure for the papillary component, the same therapy at the same dose, and showed strong tolerability and clinical benefit, including over 82% bladder preservation and more than 96% disease-specific survival at 36 months.¹

“… it is incomprehensible to me that the FDA refuses to file a supplemental BLA, stating the study is not sufficient to support a regulatory review, when it has already approved a product based on that very same study in essentially the same indication and population,” said Rachel Sherman, former FDA principal deputy commissioner, in the press release.

References

1. ImmunityBio Requests an Urgent Meeting With FDA to Address the Change in the Agency’s Unambiguous Guidance on Jan 2025 to Submit a sBLA for NMIBC BCG Unresponsive Papillary Disease, Following an Inconsistent Refusal to File Letter on May 2, 2025. ImmunityBio. May 5, 2025. Accessed May 6, 2025. https://immunitybio.com/immunitybio-requests-an-urgent-meeting-with-fda-to-address-the-change-in-the-agencys-unambiguous-guidance-on-jan-2025-to-submit-a-sbla-for-nmibc-bcg-unresponsive-papillary-disease-following/

2. QUILT-3.032: A Multicenter Clinical Trial of Intravesical Bacillus Calmette-Guerin (BCG) in Combination With ALT-803 (N-803) in Patients With BCG Unresponsive High Grade Non-Muscle Invasive Bladder Cancer. Clinicaltrials.gov. Accessed May 6, 2025. https://clinicaltrials.gov/study/NCT03022825

3. ImmunityBio Completes ANKTIVA’s Post-Approval Enrollment of the 100th Patient in BCG Unresponsive NMIBC CIS Trial and Reports a Complete Response Rate of 71% with a Durable Duration of Response Ranging Up to 54 Months. BusinessWire. November 19, 2024. Accessed May 6, 2025. https://www.businesswire.com/news/home/20241119975432/en/ImmunityBio-Completes-ANKTIVAs-Post-Approval-Enrollment-of-the-100th-Patient-in-BCG-Unresponsive-NMIBC-CIS-Trial-and-Reports-a-Complete-Response-Rate-of-71-with-a-Durable-Duration-of-Response-Ranging-Up-to-54-Months