FDA Receives Resubmitted BLA for Tabelecleucel in EBV+ Post-Transplant Lymphoproliferative Disease

FDA

The FDA has received a resubmitted biologics license application (BLA) seeking the approval of tabelecleucel (tab-cel; Ebvallo) as monotherapy for 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 follows a complete response letter (CRL) issued by the FDA in January 2025 for the initial BLA.2 In the CRL, the FDA cited issues raised during an inspection of a third-party manufacturing facility. No issues regarding efficacy or safety data were identified, and no additional clinical studies were requested to support the BLA resubmission.

“The BLA resubmission for tab-cel represents the collaborative efforts with our partner, Pierre Fabre Laboratories, to address the third-party manufacturing facility observations outlined in the January 2025 CRL,” Cokey Nguyen, PhD, president and chief executive officer of Atara Biotherapeutics, stated in a news release.1 “We look forward to continued engagement with the FDA throughout its review and with Pierre Fabre Laboratories as they actively prepare for the potential launch of this innovative therapy in the US.”

The BLA is supported by data from the phase 3 ALLELE trial (NCT03394365). Updated findings presented at the 2024 ASH Annual Meeting demonstrated that evaluable patients with relapsed/refractory EBV-positive PTLD treated with tab-cel (n = 75) achieved an objective response rate (ORR) of 50.7%.3 The ORR was 51.0% in patients who underwent a solid organ transplant (n = 49) and 50.0% in those who received a hematopoietic stem cell transplant (n = 26).

In the overall cohort, patients achieved a median duration of response (DOR) of 23 months and a median overall survival (OS) of 18.4 months.

Regarding safety, serious treatment-emergent adverse effects (TEAEs) occurred at a rate of 65.4% of HSCT recipients treated with tab-cel and 61.2% in patients who received a solid organ transplant. The respective rates of fatal TEAEs were 19.2% and 18.4%. No fatal TEAEs were treatment related, and no instances of cytokine release syndrome, tumor flare or infusion reactions, immune effector cell–associated neurotoxicity syndrome, or transmission of infectious diseases were reported. No graft-vs-host disease or organ rejection related to tab-cel were reported.

The multicenter, open-label ALLELE study enrolled patients with locally assessed, biopsy-proven EBV-positive PTLD who underwent prior solid organ transplant or HSCT.4 Prior treatment with rituximab (Rituxan) with or without chemotherapy was required. Patients at least 16 years of age needed to have an ECOG performance status of 0 to 3, and those under 16 years of age were required to have a Lansky performance status of at least 20. For patients who received an allogeneic HSCT as treatment for an acute lymphoid or myeloid malignancy, the underlying primary disease needed to be in morphologic remission.

Patients with Burkitt lymphoma, classical Hodgkin lymphoma, or any T-cell lymphoma were excluded from the trial. Those with untreated central nervous system (CNS) PTLD or CNS PTLD being actively treated with CNS-directed chemotherapy or radiotherapy were disqualified; however, patients with CNS PTLD were allowed to enroll if CNS-directed therapy was complete.

Patients were assigned to 1 of 3 cohorts, where all patients received tab-cel. The 3 cohorts included solid organ transplant recipients who received prior treatment with rituximab; solid organ transplant recipients who were previously treated with rituximab and chemotherapy; and HSCT recipients who previously received a rituximab-containing regimen.

ORR served as the trial’s primary end point. Secondary end points comprised DOR; ORR and DOR by transplant type; complete response rate; time to response; time to best response; OS; and rates of allograft loss or rejection.

References

1. Atara Biotherapeutics provides regulatory and business updates on tabelecleucel (tab-cel). News release. Atara Biotherapeutics. July 14, 2025. Accessed July 14, 2025. https://investors.atarabio.com/news-events/press-releases/detail/375/atara-biotherapeutics-provides-regulatory-and-business
2. Atara Biotherapeutics provides regulatory and business update on Ebvallo (tabelecleucel). News release. Atara Biotherapeutics. January 16, 2025. Accessed July 14, 2025. https://investors.atarabio.com/news-events/press-releases/detail/367/atara-biotherapeutics-provides-regulatory-and-business
3. Updated results of phase 3 ALLELE study presented at 66th American Society of Hematology Annual Meeting confirm efficacy, safety and durability of novel allogeneic cell therapy tabelecleucel in relapsed or refractory Epstein-Barr virus positive post-transplant lymphoproliferative disease (EBV+ PTLD). News release. Pierre Fabre Pharmaceuticals. December 7, 2024. Accessed July 14, 2025. https://www.pierrefabrepharmaceuticals.com/press/20241207_PR_ASH_2024_tabelecleucel_ALLELE_results_safety_efficacy_durability.pdf
4. Tabelecleucel for solid organ or allogeneic hematopoietic cell transplant participants With Epstein-Barr virus-associated post-transplant lymphoproliferative disease (EBV+ PTLD) after failure of rituximab or rituximab and chemotherapy (ALLELE). ClinicalTrials.gov. Updated July 14, 2025. Accessed July 14, 2025. https://clinicaltrials.gov/study/NCT03394365