FDA Completes Type A Meeting Following CRL for Tabelecleucel in EBV+ R/R Post-Transplant Lymphoproliferative Disease

The FDA and Atara Biotherapeutics completed a Type A meeting to discuss the complete response letter (CRL) issued by the regulatory agency for the biologics license application (BLA) seeking the approval of tabelecleucel (tab-cel; Ebvallo) for the treatment of patients with Epstein-Barr virus (EBV)–positive, relapsed/refractory post-transplant lymphoproliferative disease (PTLD).¹

The initial BLA for tab-cel received a CRL in January 2025, with the FDA citing a single good manufacturing practices (GMP)–related deficiency as the reason for the rejection.² In the second CRL issued by the FDA in January 2026, the regulatory agency acknowledged that the GMP issue was resolved; however, the FDA said it no longer considered data from the single-arm, phase 3 ALLELE trial (NCT03394365) as adequate to support accelerated approval and called for a new study.

In the Type A meeting, the FDA agreed that a single-arm study with an appropriate, prespecified historical control applicable to the trial population could represent an adequate and well-controlled study to support a future BLA for tab-cel in this indication.¹ As part of the resubmission plan being defined by the FDA, Pierre Fabre Pharmaceuticals (PFP) intends to submit an updated dataset that includes additional patients and longer-term follow-up from ALLELE, along with supportive data.

“We are grateful to the agency for engaging in a collaborative conversation with our partners, PFP, and us. We appreciate the FDA’s continued engagement with PFP and Atara, and we believe the Type A Meeting provided helpful alignment on the regulatory framework to resubmit,” Cokey Nguyen, president and chief executive officer of Atara Biotherapeutics, stated in a news release. “We will continue to support PFP as it prepares the resubmission and anticipate providing a further regulatory update in the third quarter [of 2026].”

What were the findings from ALLELE supporting the BLA seeking the approval of tab-cel for PTLD?

ALLELE was a global, multicenter, open-label, phase 3 trial that enrolled patients of any age with EBV-associated PTLD who experienced progression on rituximab (Rituxan) or a commercially available biosimilar with or without chemotherapy in the setting of either solid organ transplant (SOT) or hematopoietic stem cell transplantation (HSCT).^3,4

The nonrandomized study included 3 cohorts, where all patients received tab-cel at 2 × 10⁶ cells/kg on days 1, 8, and 15 in 35-day cycles.^3,4 The 3 cohorts included:³

• Patients with EBV-positive PTLD following SOT who had progressed on only rituximab
• Patients with EBV-positive PTLD following SOT who had progressed on both rituximab and chemotherapy
• Patients with EBV-positive PTLD following HSCT who had progressed on rituximab

Objective response rate (ORR) served as the trial’s primary end point. Secondary end points included duration of response (DOR), complete response rate, time to response, time to best response, overall survival (OS), and rates of allograft loss or rejection episodes.

Finding published in Lancet Oncology showed that among patients who underwent prior HSCT (n = 14), the ORR was 50% (95% CI, 23%-77%) at a median follow-up of 6.0 months (interquartile range [IQR], 1.8-18.4).⁴ In those who underwent prior SOT (n = 29), the ORR was 52% (95% CI, 33%-71%) at a median follow-up of 14.1 months (IQR, 5.7-23.9).

Safety data showed that serious treatment-emergent adverse effects (TEAEs) occurred in 53% of evaluable patients (n = 43). Additionally, 12% of patients experienced fatal TEAEs, but no deaths due to TEAEs were deemed treatment related.

Updated findings presented at the 2024 ASH Annual Meeting and Exposition showed that in a larger cohort featuring 75 patients (prior SOT, n = 49; prior HSCT, n = 26), the ORR was 51.0% in the SOT cohort and 50.0% in the HSCT cohort.⁵ The median DOR and median OS for the overall population were 23 months and 18.4 months, respectively.

References

1. Atara Biotherapeutics provides regulatory update on tabelecleucel. News release. Atara Biotherapeutics. May 7, 2026. Accessed May 7, 2026. https://investors.atarabio.com/news-events/press-releases/detail/385/atara-biotherapeutics-provides-regulatory-update-on
2. Pierre Fabre Pharmaceuticals statement regarding receipt of complete response letter for tabelecleucel biologics license application from the U.S. Food and Drug Administration. News Release. Pierre Fabre Pharmaceuticals. January 12, 2026. Accessed May 7, 2026. https://www.pierrefabrepharmaceuticals.com/sites/default/files/press/20260112_PS_FDA%20CRL%20on%20EBVALLO%20BLA.pdf
3. 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 February 20, 2026. Accessed May 7, 2026. https://clinicaltrials.gov/study/NCT03394365
4. 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
5. 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 May 7, 2026. https://www.prnewswire.com/news-releases/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--302325211.html