FDA Hits Atara Biotherapeutics’ T-Cell Immunotherapy Tabelecleucel for EBV+ PTLD With Second CRL

This is a developing story and will be updated with new information as it becomes available.

The FDA has issued a new complete response letter to Atara Biotherapeutics' regarding its biologics license application (BLA) for allogeneic Epstein-Barr virus (EBV)–specific T-cell immunotherapy tabelecleucel (tab-cel; marketed as Ebvallo) for the treatment of patients 2 years or older with EBV-positive posttransplant lymphoproliferative disease (EBV+ PTLD) who have received at least 1 prior therapy.¹

The CRL indicates that the FDA did not find the data from the pivotal phase 3 ALLELE clinical trial (NCT03394365) supporting the BLA to provide sufficient evidence of tab-cel’s efficacy. In addition, the agency claims that ALLELE’s design, conduct, and analysis confounds the interpretability of the trial.

Notably, the CRL is the second Atara has received from the FDA for a tab-cel BLA. Atara first submitted a BLA for tab-cel to the FDA in May 2024, but that BLA was met with a complete response letter (CRL) in January 2025.^3,4 The first CRL was related to issues with a standard prelicense inspection of a third-party manufacturer for tab-cel rather than to any concerns regarding the efficacy and safety data for the therapy itself; furthermore, the manufacturing process itself was not implicated, and the FDA did not request additional clinical trials.

Atara submitted its second BLA for tab-cel following the initial CRL, and this new BLA was accepted by the FDA in July 2025.² In the second CRL, the FDA confirmed that the good manufacturing practice (GMP) compliance issue that was the basis of the first CRL had been resolved and did not raise any new issues relate to safety.¹

As such, Atara considers the new CRL to be a contradiction of earlier communications and expectations. Notably, Atara had transferred the BLA for tab-cel to Pierre Fabre Pharmaceuticals (PFP) in November 2025 and PFP plans to request a type A meeting with the FDA with the intent of finding a means to accelerated approval of tab-cel.

“We are surprised and disappointed by this FDA decision for EBV+ PTLD patients who have a significant unmet need, highlighted by tabelecleucel’s orphan drug designation and by the granting of breakthrough status at the time we submitted the ALLELE primary data,” Cokey Nguyen, PhD, the president and chief executive officer of Atara, said in a statement.¹. “The issues highlighted in the CRL were issues Atara and the FDA aligned on in previous reviews or communications. We had aligned with the agency to accept an accelerated approval and to perform a post marketing confirmatory study to support full approval. We proceeded with the BLA submission on this basis and continued all remediation efforts after the resubmission in 2025, in full reliance of the confirmation provided by the FDA. We strongly believe that tab-cel can bring substantial benefit to PTLD patients, and look forward to addressing the concerns of the FDA clinical review team newly in place alongside our partners.”

The BLA was supported by data from the pivotal phase 3 ALLELE clinical trial (NCT03394365) and other studies that cumulatively include greater than 430 patients with multiple diseases.² Notably, a 48.8% objective response rate was observed in ALLELE (P < .0001) in the most up-to-date data, and according to Atara, the safety profile of tab-cel in the trial was favorable and in line with earlier analyses.

“In the new CRL, despite acknowledging that the GMP issue had been resolved and raising no safety concerns, the FDA stated that it no longer considers the previously accepted single-arm ALLELE study to be adequate to support accelerated approval and requested a new study,” PFP wrote in a press release regarding the second CRL.⁵ “This represents a significant and unexpected change in position, and one that is contrary to extensive dialogue with the Agency over more than 5 years. We are concerned that this decision may have far-reaching consequences for the development of rare disease treatments, effectively creating barriers for generating clinical evidence within a unique patient population with ultra-rare conditions thereby significantly delaying—or preventing altogether— patient access to urgently needed therapies…. We intend to engage with the FDA to urgently pursue a path forward, in collaboration with Atara Biotherapeutics and our clinical and patient partners, to enable timely accelerated approval of tabelecleucel. We continue to be committed to making tabelecleucel available to patients through our Expanded Access Program.”

Tab-cel has previously been approved in the European Union, the United Kingdom, and Switzerland for the treatment of relapsed/refractory EBV+ PTLD in patients aged 2 years and older who have received at least 1 prior therapy.³ Notably, Atara stated in January 2025 that a manufacturing facility operated by FUJIFILM Diosynth Biotechnologies and located in Thousand Oaks, California, had received approval to manufacture tab-cel for the European Medicines Agency.⁴

REFERENCES
1. Atara Biotherapeutics provides regulatory and business update on Ebvallo (tabelecleucel). News release. Atara Biotherapeutics, Inc. January 12, 2026. Accessed January 12, 2026. https://investors.atarabio.com/news-events/press-releases/detail/380/atara-biotherapeutics-provides-regulatory-and-business
2. Atara Biotherapeutics announces U.S. FDA acceptance and priority review of the biologics license application for tabelecleucel (tab-cel®) for the treatment of epstein-barr virus positive post-transplant lymphoproliferative disease. News release. Atara Biotherapeutics, Inc. July 24, 2025. Accessed July 31, 2025. https://investors.atarabio.com/news-events/press-releases/detail/376/atara-biotherapeutics-announces-u-s-fda-acceptance-and
3. Atara Biotherapeutics Submits Tabelecleucel (Tab-cel) Biologics License Application for Treatment of Epstein-Barr Virus Positive Post-Transplant Lymphoproliferative Disease with U.S. FDA. News release. Atara Biotherapeutics. May 20, 2024. Accessed July 31, 2025. https://www.businesswire.com/news/home/20240520985176/en/Atara-Biotherapeutics-Submits-Tabelecleucel-Tab-cel%C2%AE-Biologics-License-Application-for-Treatment-of-Epstein-Barr-Virus-Positive-Post-Transplant-Lymphoproliferative-Disease-with-U.S.-FDA
4. Atara Biotherapeutics provides regulatory and business update on EBVALLO (tabelecleucel). News release. Atara Biotherapeutics Inc. January 16, 2025. Accessed July 31, 2025. https://investors.atarabio.com/news-events/press-releases/detail/367/atara-biotherapeutics-provides-regulatory-and-business
5. Pierre Fabre Pharmaceuticals statement regarding receipt of complete response letter for tabelecleucel biologics license application from the U.S. Food and Drug Administration. News release. Pierre Fabre Pharmaceuticals, Inc. January 12, 2026. Accessed January 12, 2026. https://www.prnewswire.com/news-releases/pierre-fabre-pharmaceuticals-statement-regarding-receipt-of-complete-response-letter-for-tabelecleucel-biologics-license-application-from-the-us-food-and-drug-administration-302658114.html