Tabelecleucel BLA Is Resubmitted to FDA for EBV+ Post-Transplant Lymphoproliferative Disease

Pierre Fabre Pharmaceuticals (PFP) has resubmitted a biologics license application (BLA) to the FDA seeking the approval of tabelecleucel (Ebvallo) as monotherapy for the treatment of adult and pediatric patients 2 years of age and older with Epstein-Barr virus (EBV)–positive post-transplant lymphoproliferative disease (PTLD) who have received at least 1 prior therapy.¹

The resubmission was based on alignment reached with the FDA at a Type A meeting in April 2026 and includes an updated dataset with additional patients and longer follow-up from the ongoing, pivotal, single-arm phase 3 ALLELE trial (NCT03394365), along with supplemental data from expanded access programs, a separate clinical study, and commercial experience in Europe.

ALLELE findings presented at the 2024 ASH Annual Meeting and Exposition showed that patients treated with tabelecleucel (n = 75) achieved an objective response rate (ORR) of 50.7% (95% CI, 38.9%-62.4%), including a complete response rate of 28.0%; the estimated median duration of response (DOR) was 23.0 months (95% CI, 12.1-not estimable [NE]), and the median overall survival (OS) was 18.4 months (95% CI, 6.9-NE).² The primary analysis of ALLELE was published in Lancet Oncology.³

"PFP remains committed to working with the FDA to advance treatment options for people living with EBV-positive PTLD who, after undergoing a potentially life-saving solid organ or hematopoietic cell transplant, suddenly face yet another life-threatening illness, cancer," Adriana Herrera, chief executive officer of PFP, said in the news release.¹ "These patients are waiting for an FDA-approved treatment as their survival after failure of initial therapy is measured in only weeks to a few months."

What is the regulatory history of tabelecleucel in the US?

In July 2024, the FDA accepted and granted priority review to the original BLA for tabelecleucel in this population, assigning a target action date of January 15, 2025.⁴ In January 2025, the agency issued a complete response letter (CRL) related to observations from a standard prelicense inspection of a third-party manufacturing facility; no deficiencies were identified in the clinical efficacy, safety, or manufacturing data in the application, and the FDA did not request additional clinical studies.⁵

The FDA accepted a resubmitted BLA with priority review in July 2025. That application was supported by data from more than 430 patients treated with tabelecleucel, including findings from ALLELE.⁶

In January 2026, the FDA issued a second CRL.⁷ Although the agency acknowledged that the manufacturing-related issue had been resolved and did not raise safety concerns, it indicated that it no longer considered the single-arm ALLELE study sufficient to support accelerated approval and requested a new study.

At the subsequent Type A meeting, the FDA agreed that a single-arm study with an appropriate, prespecified historical control applicable to the trial population could represent an adequate and well-controlled study to support a future BLA for tabelecleucel in this indication.⁸ Atara Biotherapeutics, which is partnered with PFP on tabelecleucel, said at the time that PFP intended to submit an updated ALLELE dataset with additional patients and longer-term follow-up, along with supportive data.

What is the mechanism of action of tabelecleucel?

Tabelecleucel is an allogeneic, off-the-shelf, EBV-specific T-cell immunotherapy designed to target and attack EBV-infected cells.¹ The non–genetically modified T cells recognize EBV-infected cells in a human leukocyte antigen (HLA)–restricted manner.³

The agent received marketing authorization under the brand name Ebvallo from the European Commission in December 2022, the United Kingdom's Medicines and Healthcare Products Regulatory Agency in May 2023, and Swissmedic in May 2024.¹

EBV-positive PTLD is an ultra-rare hematologic malignancy that occurs after solid organ transplant (SOT) or allogeneic hematopoietic cell transplant (HCT) when T-cell immune responses are compromised by immunosuppression. According to PFP, median survival after failure of initial treatment is 3 weeks for patients who underwent HCT and 4.1 months for those who underwent SOT.

How was the ALLELE trial designed?

The global, multicenter, open-label ALLELE study enrolled patients of any age with biopsy-proven EBV-positive PTLD that had relapsed or was refractory to rituximab (Rituxan) or a biosimilar after allogeneic HCT, or to rituximab with or without chemotherapy after SOT.³ Patients were required to have an ECOG performance status of 3 or lower.

Patients were assigned to 1 of 3 cohorts: SOT recipients who had progressed on rituximab alone, SOT recipients who had progressed on rituximab and chemotherapy, and HCT recipients who had progressed on rituximab.⁷ All patients received intravenous tabelecleucel at 2 × 10⁶ cells/kg on days 1, 8, and 15 of each 35-day cycle. Treatment continued until maximal response, unacceptable toxicity, initiation of nonprotocol therapy, or lack of response after up to 2 HLA restrictions in the SOT cohorts or 4 restrictions in the HCT cohort.

ORR served as the primary end point. Secondary end points included DOR, OS, time to response, time to best response, and rates of allograft loss or rejection episodes.⁷

In the primary analysis published in Lancet Oncology, the ORR was 50% (95% CI, 23%-77%) among patients who had undergone HCT (n = 14) and 52% (95% CI, 33%-71%) among those who had undergone SOT (n = 29).³ In the updated ASH 2024 analysis, the ORR was 50.0% in the HCT cohort (n = 26) and 51.0% in the SOT cohort (n = 49).² The median time to response was 1.1 months (range, 0.6-9.0), the median progression-free survival was 23.9 months, and the 12-month OS rate was 55.7%.

What is the safety profile of tabelecleucel?

In the updated ALLELE analysis, serious treatment-emergent adverse effects (TEAEs) occurred in 62.7% of patients, including 8.0% that were considered related to tabelecleucel.² Serious TEAEs occurred in 65.4% of HCT recipients and 61.2% of SOT recipients, and the respective rates of fatal TEAEs were 19.2% and 18.4%; no fatal TEAEs were considered treatment-related.

No cases of tumor flare, infusion-related reactions, cytokine release syndrome, immune effector cell–associated neurotoxicity syndrome, or transmission of infectious diseases were reported, and no graft-vs-host disease or organ rejection was attributed to tabelecleucel.

References

1. Pierre Fabre Pharmaceuticals resubmits tabelecleucel biologics license application for treatment of Epstein-Barr virus positive-post-transplant lymphoproliferative disease to the FDA. News release. Pierre Fabre Pharmaceuticals. September 30, 2026. Accessed September 30, 2026. https://www.prnewswire.com/news-releases/pierre-fabre-pharmaceuticals-resubmits-tabelecleucel-biologics-license-application-for-treatment-of-epstein-barr-virus-positive-post-transplant-lymphoproliferative-disease-to-the-fda-302893397.html
2. 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
3. Mahadeo KM, Baiocchi R, Beitinjaneh A, et al. Tabelecleucel for allogeneic haematopoietic stem-cell or solid organ transplant recipients with Epstein-Barr virus-positive post-transplant lymphoproliferative disease after failure of rituximab or rituximab and chemotherapy (ALLELE): a phase 3, multicentre, open-label trial. *Lancet Oncol*. 2024;25(3):376-387. doi:10.1016/S1470-2045(23)00649-6
4. 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 17, 2024. Accessed September 30, 2026. https://www.businesswire.com/news/home/20240717492765/en
5. Atara Biotherapeutics provides regulatory and business update on EBVALLO (tabelecleucel). News release. Atara Biotherapeutics. January 16, 2025. Accessed September 30, 2026. https://investors.atarabio.com/news-events/press-releases/detail/367/atara-biotherapeutics-provides-regulatory-and-business
6. 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 24, 2025. Accessed September 30, 2026. https://www.prnewswire.com/news-releases/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-disea-302513152.html
7. 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. January 12, 2026. Accessed September 30, 2026. https://www.pierrefabrepharmaceuticals.com/sites/default/files/press/20260112_PS_FDA%20CRL%20on%20EBVALLO%20BLA.pdf
8. Atara Biotherapeutics provides regulatory update on tabelecleucel. News release. Atara Biotherapeutics. May 7, 2026. Accessed September 30, 2026. https://investors.atarabio.com/news-events/press-releases/detail/385/atara-biotherapeutics-provides-regulatory-update-on