Tab-Cel BLA Resubmitted to FDA for EBV-Positive PTLD

A biologics license application (BLA) for tabelecleucel (Ebvallo; tab-cel) has been resubmitted to the FDA seeking approval for the treatment of adults and children aged 2 years and older with relapsed/refractory Epstein-Barr virus–positive post-transplant lymphoproliferative disease (EBV+ PTLD) following solid organ transplant (SOT) or hematopoietic cell transplant (HCT).¹

The resubmission follows a type A meeting with the FDA held in April 2026, during which the agency provided feedback on a potential regulatory path forward for the application. The updated BLA includes additional patients and longer follow-up from the pivotal phase 3, single-arm ALLELE study (NCT03394365), along with supplemental data from expanded access programs, a separate clinical study, and commercial experience in Europe.

Tab-cel is an allogeneic Epstein-Barr virus (EBV)–specific T-cell immunotherapy being developed as an off-the-shelf cellular therapy. The product is intended to target EBV-infected cells in patients with EBV-associated disease.

“We are grateful to the [FDA] for their continued guidance and engagement with our partner, [Pierre Fabre Pharmaceuticals], and us,” said Cokey Nguyen, president and CEO of Atara Biotherapeutics, in a news release. “We will continue to support [our partner] as it prepares for the review process and anticipate providing a revised anticipated PDUFA date as it becomes available.”

Tab-Cel’s Regulatory History

The latest submission follows previous interactions between the companies and FDA concerning the tab-cel BLA. Atara's partner, Pierre Fabre Pharmaceuticals, holds the BLA and is leading the regulatory submission process, with Atara providing support.

The resubmission follows 2 previous CRLs from the FDA. The first, issued in January 2025, identified issues related to manufacturing following an inspection of a third-party manufacturing facility. The agency did not identify deficiencies related to clinical efficacy or safety at that time, and no additional clinical studies were requested.

Following resolution of the manufacturing-related issues, the BLA was resubmitted in July 2025 and received priority review. However, in January 2026, the FDA issued a second CRL, determining that the application could not be approved in its current form. The agency raised concerns regarding the adequacy and interpretability of the ALLELE study as support for accelerated approval.

About ALLELE

ALLELE is a pivotal, single-arm phase 3 study evaluating tab-cel in adults and children aged 2 years and older with relapsed/refractory EBV+ PTLD following SOT or HCT.² The study enrolled patients whose disease had progressed following rituximab (Rituxan)-containing therapy or, for some HCT recipients, when rituximab was not appropriate.

In the data set supporting the original BLA, tab-cel demonstrated an objective response rate (ORR) of 48.8% (P <.0001). In subsequent analyses, the overall ORR was 50.7% (95% CI, 38.9%-62.4%).³ The ORR was 51.0% (95% CI, 36.3%-65.6%) among patients in the SOT cohort and 50.0% (95% CI, 29.9%-70.1%) among those in the HCT cohort.⁴

The safety profile previously reported for the ALLELE study included no cases of cytokine release syndrome, infusion reactions, or graft-vs-host disease. Serious treatment-emergent adverse events occurred in 65.4% of patients in the HCT cohort and 61.2% of patients in the SOT cohort.

REFERENCES

1. Atara Biotherapeutics Reports that the Tabelecleucel Biologics License Application Has Been Resubmitted to the U.S. Food and Drug Administration. News release. Atara Biotherapeutics. September 30, 2026. Accessed September 30, 2026. https://tinyurl.com/mrxych5p

2. A phase 3 study of tabelecleucel for participants with Epstein–Barr virus–associated post-transplant lymphoproliferative disease after failure with rituximab or rituximab and chemotherapy (ALLELE). ClinicalTrials.gov. Updated September 2, 2026. Accessed September 30, 2026. https://www.clinicaltrials.gov/study/NCT03394365

3. 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. July 24, 2025. Accessed September 30, 2026. https://tinyurl.com/3m782yxb

4. Ghobadi A, Baiocchi R, Beitinjaneh AM, et al. Updated clinical results: a multicenter, open-label, phase 3 study of tabelecleucel for solid organ or allogeneic hematopoietic cell transplant recipients with Epstein–Barr virus-driven post-transplant lymphoproliferative disease after failure of rituximab or rituximab plus chemotherapy. Blood. 2024;144(suppl 1):70. doi:10.1182/blood-2024-198159