FDA Grants Priority Review to Tab-Cel for EBV+ PTLD After Prior Therapies

The FDA has accepted the biologics license application (BLA) of tabelecleucel (tab-cel; Ebvallo) for priority review in adult and pediatric patients aged 2 years and older with relapsed or refractory Epstein-Barr virus-positive posttransplant lymphoproliferative disease (EBV+ PTLD) who have received at least 1 prior therapy. A Prescription Drug User Fee Act (PDUFA) target action date of January 10, 2026, is set.¹

EBV+ PTLD is a rare and aggressive hematologic malignancy that can develop in individuals following hematopoietic cell transplant (HCT) or solid organ transplant (SOT). The condition arises due to impaired T-cell immune surveillance caused by necessary immunosuppression, leading to uncontrolled proliferation of EBV-infected B-cells. Patients with relapsed or refractory EBV+ PTLD face a dire prognosis, with current treatment options being limited and often failing to significantly extend survival beyond weeks or months. The potential approval of tab-cel represents a critical advancement for a patient population with high unmet medical needs.

"Patients diagnosed with relapsed or refractory EBV+ PTLD have no approved FDA treatment options, and following failure of initial therapy their survival is unfortunately measured in only weeks to months. Today's BLA acceptance gives hope to these patients and is a significant step towards making this innovative cell therapy available in the United States," said Adriana Herrera, CEO of PFP, the Pierre Fabre Laboratories Pharmaceutical subsidiary in the US, in a press release. "We are now completely focused on preparing for potential FDA approval of this innovative new treatment option."

Tab-cel is an allogeneic, off-the-shelf T-cell immunotherapy engineered to specifically target and eliminate EBV-infected cells. Its mechanism of action involves the direct recognition and lysis of EBV-expressing cells, a critical feature given the oncogenic role of EBV in PTLD. This targeted approach aims to restore antiviral immunity without broadly impacting the immune system, which is particularly crucial in a transplant setting where patients are already immunocompromised.

The BLA submission is supported by a comprehensive clinical development program, including data from over 430 patients. A pivotal component of this submission is the ongoing phase 3 ALLELE study (NCT03394365), a global, multicenter, open-label trial evaluating the efficacy and safety of tab-cel in patients with biopsy-proven EBV+ PTLD who have relapsed or are refractory to rituximab (after allogeneic HCT) or rituximab with or without chemotherapy (following SOT).

Early results from the ALLELE study have demonstrated clinically meaningful objective response rates and a favorable safety profile across both HCT and SOT cohorts, supporting the therapy’s potential to address this challenging disease. Previous data showed an overall response rate of 50.7% (95% CI, 38.9%–62.4%) in the overall patient population, comprising complete and partial responses.

The current BLA resubmission by Atara Biotherapeutics Inc., in collaboration with Pierre Fabre Pharmaceuticals Inc., follows the resolution of manufacturing facility observations cited in a January 2025 complete response letter.² In May 2025, the FDA lifted the clinical hold on the investigational new drug application of tab-cel,³ and the BLA for tab-cel was resubmitted to the FDA on July 11, 2025.⁴

REFERENCES:

1. Pierre Fabre Pharmaceuticals Inc. Announces FDA Acceptance and Priority Review of the Biologics License Application (BLA) for Tabelecleucel for the Treatment of Epstein-Barr Virus Positive Post-Transplant Lymphoproliferative Disease (EBV+ PTLD). News release. Pierre Fabre Pharmaceuticals. July 25, 2025. Accessed July 25, 2025. https://tinyurl.com/2yuz9cwa

2. Atara Biotherapeutics provides regulatory and business update on EBVALLO (tabelecleucel). News release. Atara Biotherapeutics. January 16, 2025. Accessed July 25, 2025. https://tinyurl.com/yuc4d6jy

3. Atara Biotherapeutics provides regulatory updates on Ebvallo™ (tabelecleucel). News release. Atara Biotherapeutics. May 5, 2025. Accessed July 25, 2025. https://tinyurl.com/ycycpv9r

4. Pierre Fabre Pharmaceuticals, Inc. announces transfer of investigational new drug application for tabelecleucel from Atara Biotherapeutics, Inc. News release. July 15, 2025. Accessed July 25, 2025. https://tinyurl.com/ynhf9c7a