Pierre Fabre's Tabelecleucel Advances in EBV+ PTLD, FDA Review Pending

Pierre Fabre Pharmaceuticals is spearheading the global development of tabelecleucel (tab-cel), an innovative therapy designed to treat Epstein-Barr virus-positive post-transplant lymphoproliferative disorder (EBV+ PTLD). With ongoing clinical trials and a recent resubmission of the biologics license application (BLA) to the U.S. Food and Drug Administration (FDA), the drug is on the cusp of potential approval, offering hope to patients suffering from this rare and often fatal condition.

The pivotal phase 3 ALLELE study (NCT03394365) is currently enrolling patients who have relapsed or refractory EBV+ PTLD following solid organ or hematopoietic cell transplantation. According to Dr. Cokey Nguyen, President and CEO of Atara Biotherapeutics, “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 complete response letter (CRL).” The initial application was denied in January 2025 due to issues unrelated to the safety and efficacy data, with no additional clinical studies required for the resubmission.

EBV+ PTLD is characterized by the uncontrolled proliferation of EBV-infected B-cells, typically arising in immunocompromised patients post-transplant. Historical data indicates a median survival of only three weeks for patients who underwent hematopoietic stem cell transplantation (HSCT) and just over four months for solid organ transplant recipients after failing standard therapies like rituximab. The urgent need for effective treatments highlights the significance of tab-cel, which is an off-the-shelf, allogeneic T-cell therapy engineered to target and eliminate EBV-infected cells.

In the ongoing ALLELE trial, preliminary data presented at the 2024 American Society of Hematology Annual Meeting revealed an objective response rate (ORR) of 50.7% among 75 evaluable patients. The median duration of response was reported at 23 months, while median overall survival was 18.4 months, indicating promising outcomes for this patient population. Notably, the therapy demonstrated a favorable safety profile, with serious treatment-emergent adverse events occurring in 65.4% of HSCT patients and 61.2% of solid organ transplant patients, yet no cases of cytokine release syndrome were observed.

In addition to the ALLELE trial, a second phase 2 study (NCT04554914) is actively enrolling patients with a broader spectrum of EBV-associated diseases, aiming to expand the therapeutic potential of tab-cel. As the drug navigates the regulatory review process in the U.S., it is poised to become a cornerstone therapy for EBV+ malignancies, particularly if it receives FDA approval following the European Commission’s authorization in 2022. Should this occur, oncologists in the U.S. will gain access to the first allogeneic T-cell therapy for this aggressive disease, potentially transforming the treatment landscape for affected patients.

The implications of tab-cel's approval could extend beyond immediate patient care, influencing future research directions and investment in similar therapies targeting viral-associated malignancies. As drug development in oncology continues to evolve, the case of tab-cel serves as a reminder of the critical need for innovative solutions in the face of rare but life-threatening conditions.