FDA Accepts BLA, Grants Priority Review to Tab-Cel in EBV-Positive PTLD

Following the lifting of a clinical hold, the FDA has again accepted the BLA for tabelecleucel in adult and pediatric patients with EBV-positive PTLD.

The FDA has accepted the biologics license application (BLA) and granted priority review to tabelecleucel (tab-cel; Ebvallo) monotherapy in adult and pediatric patients 2 years of age or older with Epstein-Barr virus (EBV)–positive post-transplant lymphoproliferative disease (PTLD) who received at least 1 prior line of therapy, according to a press release from Pierre Fabre Pharmaceuticals (PFP).1

The FDA has set a Prescription Drug User Fee Act target action date of January 10, 2026. If approved, it would be the first approved therapy in the US for EBV-positive PTLD.

Previously, the FDA accepted the submitted BLA for tab-cel in the proposed indication in July 2024; in January 2025, the FDA then issued a complete response letter to the developer due to observations as part of a pre-license inspection of a third-party manufacturing facility for tab-cel; in May 2025, the clinical hold was lifted after the agency reviewed additional data on the finished drug product; and in July 2025, the developers resubmitted the BLA for tab-cel in the proposed indication.2-5

The phase 3 ALLELE trial (NCT03394365) evaluated the efficacy and safety of tab-cel in this population of patients with EBV-positive PTLD who previously received solid organ transplant or hematopoietic cell transplantation; results from the trial supported the FDA’s decision. Updated results were shared at the 51st Annual European Society for Blood and Marrow Transplantation Meeting.

“Patients diagnosed with relapsed/refractory EBV-positive 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 US,” stated Adriana Herrera, chief executive officer of PFP, in the press release.1 “We are now completely focused on preparing for potential FDA approval of this innovative new treatment option.”

The overall response rate (ORR) with tabelecleucel in all patients (n = 75) was 50.7% (95% CI, 38.9%-62.4%), with a complete response (CR) rate of 28.0% and a partial response (PR) rate of 22.7%. Patients who underwent hematopoietic stem cell transplant (HSCT; n = 26) demonstrated an ORR of 50.0%, with a CR rate of 30.8% and a PR rate of 19.2%; those who underwent solid organ transplant (n = 49) had an ORR of 51.0%, with a CR rate of 24.5% and a PR rate of 26.5%.

The estimated median duration of response was 23.0 months (95% CI, 12.1-not evaluable [NE]) for all responders, 19.0 months (95% CI, 1.5-NE) for responders who underwent HSCT (n = 13), and NE (95% CI, 6.8-NE) for responders who underwent solid organ transplant (n = 25). The median time to response and time to best response, respectively, was 1.1 months (95% CI, 0.6-9.0) and 1.6 months (95% CI, 0.6-9.0) in all patients, 1.0 months (95% CI, 0.6-9.0 and 1.0 months (95% CI, 0.6-9.0) in those who underwent HSCT, and 2.0 months (95% CI, 0.7-4.7) and 2.1 months (95% CI, 0.7-7.3) in those who underwent solid organ transplant.

The median overall survival (OS) was 18.4 months (95% CI, 5.7-NE) in all patients, NE (95% CI, 18.6 months-NE) in responders, and 3.7 months (95% CI, 1.8-11.0) in nonresponders; the 12-month OS rates were 55.7%, 78.7%, and 28.2%, respectively. Among responders, the median PFS was 23.9 months, and the 12-month PFS rate was 71.9%.

The trial enrolled patients with biopsy-proven EBV-positive PTLD who were relapsed/refractory to rituximab (Rituxan) following prior allogeneic HSCT or rituximab with or without chemotherapy after solid organ transplant; they were required to have an ECOG performance status of 3 or lower.

Tab-cel was administered intravenously at 2.0 x 106 cells/kg on days 1, 8, and 15 of each 5-week treatment cycle; additional tab-cel was given until patients achieved best response, and those who did not respond were permitted to switch to tab-cel using a T-cell line with different HLA restrictions.

The trial’s primary end point was ORR. Key secondary end points were time to response, time to best response, OS, and PFS.

Regarding safety, treatment-emergent serious adverse effects (AEs) occurred in 62.7% of all patients; 8.0% were related to treatment. All fatal treatment-emergent serious AEs were not related to treatment.

Instances of tumor flare reactions, infusion-related reactions, cytokine release syndrome, bone marrow rejection, and immune effector cell-associated neurotoxicity syndrome were not reported by any patients.

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 28, 2025. https://tinyurl.com/5hfdh7cn
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. Published July 17, 2024. Accessed July 28, 2025. https://tinyurl.com/yc4dx6yk
3. Atara Biotherapeutics provides regulatory and business update on EBVALLO™ (tabelecleucel). News release. Atara Biotherapeutics. January 16, 2025. Accessed July 28, 2025. https://tinyurl.com/3p9jrrtj
4. Atara Biotherapeutics provides regulatory updates on EBVALLO (tabelecleucel). News release. Atara Biotherapeutics Inc. May 5, 2025. Accessed July 28, 2025. https://tinyurl.com/3cekvud5
5. Atara Biotherapeutics provides regulatory and business updates on tabelecleucel (tab-cel). News release. Atara Biotherapeutics Inc. July 14, 2025. Accessed July 28, 2025. https://tinyurl.com/25pxk95y
6. Dierick D, Ghobadi A, Baiocchi R, et al. Updated results: multicenter open-label ph 3 study of tabelecleucel for SOT or HCT recipients with EBV+ PTLD after failure of rituximab or rituximab + chemotherapy. Presented at: EBMT 51st Annual Meeting; March 30-April 2, 2025. Florence, Italy. Abstract OS17-03.