FDA Grants Priority Review to Resubmitted BLA for Tabelecleucel in EBV+ Post-Transplant Lymphoproliferative Disease

FDA

The FDA has granted priority review to a resubmitted biologics license application (BLA) seeking the approval of tabelecleucel (Ebvallo) 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

Acceptance of the BLA follows the resolution of issues cited in a complete response letter (CRL) issued by the FDA on January 16, 2025, related to observations from a standard prelicense inspection of a third-party manufacturing facility.2 No deficiencies were identified with the clinical efficacy, safety, or manufacturing data submitted in the application, and the FDA did not request additional clinical trials to support approval.

The BLA is supported by data from more than 430 patients treated with tabelecleucel, including findings from the phase 3 ALLELE study (NCT03394365), evaluating tabelecleucel in patients with relapsed or refractory EBV-positive PTLD following solid organ transplantation (SOT) or hematopoietic stem cell transplantation (HSCT).1

"Patients diagnosed with relapsed or 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 United States," Adriana Herrera, chief executive officer of PFP, the Pierre Fabre Laboratories Pharmaceutical subsidiary in the United States, stated in a news release. "We are now completely focused on preparing for potential FDA approval of this innovative new treatment option."

In December 2022, the European Commission approved tabelecleucel for the treatment of adult and pediatric patients 2 years of age and older with relapsed or refractory EBV-positive PTLD who have received at least 1 prior therapy. The agent was also approved in this indication in the United Kingdom in May 2023 and Switzerland in May 2024.

ALLELE Study Breakdown

Updated findings from ALLELE presented at the 2024 ASH Annual Meeting showed that among treated patients (n = 75), the overall response rate (ORR) was 50.7% (95% CI, 38.9%-62.4%), which included a complete response rate of 28.0%.3 The median time to response (TTR) was 1.1 months (range, 0.6-9.0), and the estimated median duration of response was 23.0 months (95% CI, 12.1-not estimable [NE]). The median PFS was 23.9 months, and patients experienced a 12-month PFS rate of 74.2%. The median overall survival (OS) was 18.4 months (95% CI, 6.9-NE), and the 12-month OS rate was 55.7%.

Regarding safety, treatment-emergent adverse effects (TEAEs) of any grade occurred in 62.7% of patients, including 8.0% who experienced AEs related to tabelecleucel. No fatal TEAEs were related to treatment. Importantly, no cases of tumor flare, infusion-related reactions, cytokine release syndrome, bone marrow rejection, immune effector cell–associated neurotoxicity syndrome, immunogenicity, or infectious disease transmission were observed.

ALLELE was a global, multicenter, open-label study designed to evaluate tabelecleucel in patients with biopsy-confirmed EBV-positive PTLD whose disease was relapsed or refractory following rituximab (Rituxan)-based therapy. Eligible patients included those who had previously undergone either HSCT or SOT and had an ECOG performance status of 3 or lower.

Participants received intravenous tabelecleucel at a dose of 2.0 x 10⁶ cells/kg on days 1, 8, and 15, followed by clinical and radiographic evaluation at day 28. Subsequent disease assessments occurred every 3 months for up to 2 years, and survival status was monitored biannually for up to 5 years.

The study's primary end point was ORR, with secondary end points including TTR, time to best response, OS, PFS, and incidence of allograft loss or rejection.

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 24, 2025. Accessed July 24, 2025. 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
2. Atara Biotherapeutics provides regulatory and business update on Ebvallo (tabelecleucel). News release. Atara Biotherapeutics. January 16, 2025. Accessed July 24, 2025. https://investors.atarabio.com/news-events/press-releases/detail/367/atara-biotherapeutics-provides-regulatory-and-business
3. 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