FDA Grants Priority Review to Tabelecleucel for Adult/Pediatric EBV+ Post-Transplant Lymphoproliferative Disease

Pascal Touchon, MBA

The biologics license application (BLA) seeking the approval of tabelecleucel (tab-cel) monotherapy for the treatment of adult and pediatric patients who are at least 2 years of age with Epstein-Barr virus (EBV)–positive post-transplant lymphoproliferative disease following at least 1 prior therapy has been accepted by the FDA. Additionally, the BLA was granted priority review by the agency, with a Prescription Drug User Fee Act target action date of January 15, 2025.¹

Notably, there are no treatments currently approved by the FDA in this setting. The BLA is supported by findings from over 430 patients with multiple life-threatening diseases who received tab-cel, including findings from the pivotal phase 3 ALLELE trial (NCT03394365). Results from ALLELE showed that tab-cel displayed an objective response rate (ORR) of 48.8% (P < .0001) with a favorable safety profile.

“The acceptance of the tab-cel BLA is a significant milestone towards making this first-of-its-kind treatment available to patients in the US,” Pascal Touchon, MBA, president and CEO of Atara Biotherapeutics, Inc., said in a press release.¹ “The FDA’s granting of priority review highlights the high unmet need in EBV-positive post-transplant lymphoproliferative disease, which is a devastating disease with limited treatment options and a poor overall survival [OS] rate. We continue to work closely with the Pierre Fabre Laboratories team to help prepare for the potential launch in the US in early 2025, along with the potential label expansion multicohort phase 2 EBVision trial [NCT04554914].”

Tab-cel is an allogeneic T-cell immunotherapy that is specific to EBV. The agent is designed to target and kill cells infected with EBV. Previously, tab-cel received breakthrough therapy designation and orphan drug designation for the treatment of rituximab (Rituxan)-refractory EBV-associated lymphoproliferative disease by the FDA.

ALLELE was a global, multicenter, open-label study of tab-cel in patients of any age with biopsy-proven EBV-positive post-transplant lymphoproliferative disease that was relapsed/refractory to rituximab after hematopoietic stem cell transplantation (HSCT) and rituximab with or without chemotherapy following solid organ transplant. The primary end point was ORR; secondary end points included OS, duration of response, time to response, and safety.²

Previous findings from ALLELE, which were published in The Lancet Oncology, demonstrated that, at a median follow-up of 14.1 months (IQR, 5.7-23.9), patients who received HSCT (n = 14) achieved an ORR of 50% (95% CI, 23%-77%). At a median follow-up of 6.0 months (IQR, 1.8-18.4), patients who received solid organ transplant (n = 29) achieved an ORR of 52% (95% CI, 33%-71%).

In terms of safety, the most common grade 3 or 4 treatment-emergent adverse effects (TEAEs) in the HSCT and solid organ transplant groups included disease progression (29% vs 28%) and decreased neutrophil count (29% vs 14%). Serious TEAEs occurred in 53% of patients overall and TEAEs leading to death were reported in 12%. No TEAEs leading to death were deemed to be treatment-related.

Atara announced the closing of the expanded global partnership with Pierre Fabre Laboratories for the US and remaining global commercial markets for tab-cel in December 2023. Atara will receive a $20 million milestone payment from Pierre Fabre following the acceptance of the BLA for tab-cel, with the potential to receive an additional $60 million milestone payment from Pierre Fabre contingent upon the FDA approval of the agent. Additionally, Pierre Fabre is reimbursing Atara for expected tab-cel global development costs through the BLA transfer and purchasing tab-cel inventory through the manufacturing transfer date. Atara will be eligible to receive sales milestones and double-digit tiered royalties on net sales of tab-cel in the US and remaining global commercial markets.¹

Moreover, tab-cel received marketing authorization from the European Commission under the brand name Ebvallo in December 2022. The agent also received marketing authorization from the Medicines and Healthcare Products Regulatory Agency in the United Kingdom in May 2023 and by Swissmedic in Switzerland in May 2024. It is indicated as monotherapy for the treatment of adult and pediatric patients 2 years of age and older with relapsed or refractory EBV-positive post-transplant lymphoproliferative disease treated with at least 1 prior therapy.

References

1. 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 July 17, 2024. https://www.businesswire.com/news/home/20240717492765/en
2. 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