FDA CRL for EBVALLO (tabelecleucel): Atara Biotherapeutics and Pierre Fabre face rejection for EBV+ PTLD therapy despite resolved GMP issues. FDA reverses on ALLELE trial data; Type A meeting planned. Urgent path needed for rare post-transplant patients
Written By: Pharmacally Medical News Desk
Atara Biotherapeutics, Inc. has announced that the U.S. Food and Drug Administration has issued a Complete Response Letter (CRL) for the Biologics License Application (BLA) of EBVALLO (tabelecleucel), an investigational allogeneic T-cell therapy for patients with Epstein-Barr virus–positive post-transplant lymphoproliferative disease (EBV+ PTLD). The application sought accelerated approval for EBVALLO as a monotherapy in adult and pediatric patients aged two years and older who have received at least one prior therapy, including an anti-CD20 regimen.
FDA decision and background
According to Atara, the CRL states that the FDA is unable to approve the BLA in its current form. This decision follows a resubmission made in 2025, after Atara had addressed the concerns outlined in an earlier CRL issued on 15 January 2025. That first CRL identified a single deficiency related to Good Manufacturing Practice (GMP) compliance and did not raise concerns regarding safety, efficacy, or clinical trial design.
In the latest CRL, received after market close on 9 January 2026, the FDA confirmed that the previously cited GMP compliance issues have now been fully resolved. Importantly, the agency did not raise any new safety concerns related to EBVALLO.
Shift in FDA stance on clinical evidence
Despite resolving manufacturing issues, the FDA took a new position on the clinical data supporting the application. The agency stated that the single-arm ALLELE trial, which had previously been acknowledged as adequate to support the BLA, is no longer considered sufficient evidence of effectiveness for accelerated approval. The FDA further noted that the interpretability of the trial results is confounded due to aspects of study design, conduct, and analysis.
Atara emphasized that this position represents a reversal from prior FDA guidance. Over more than five years, the company and the FDA held multiple documented meetings that, according to Atara, confirmed alignment on the single-arm design of the ALLELE study and its suitability for this rare and life-threatening patient population at the time of BLA submission.
Role of Pierre Fabre and next steps
In November 2025, the BLA for EBVALLO was transferred to Pierre Fabre Pharmaceuticals. Following receipt of the CRL, Pierre Fabre Pharmaceuticals plans to request a Type A meeting with the FDA, which is expected to be scheduled within 45 days. Both companies intend to engage urgently with the agency to identify a path forward toward accelerated approval.
The companies highlighted that patients with EBV+ PTLD have extremely limited treatment options, with life expectancy often measured in weeks to months, underscoring the urgency of regulatory clarity.
Company perspective
Cokey Nguyen, President and Chief Executive Officer of Atara Biotherapeutics, expressed surprise and disappointment with the FDA’s decision. He noted that EBVALLO has received Orphan Drug designation and previously benefited from Breakthrough Therapy status at the time of submission of the ALLELE primary data. According to Nguyen, the issues cited in the latest CRL had already been discussed and aligned upon in prior FDA communications, including agreement on an accelerated approval pathway supported by a post-marketing confirmatory study.
Atara stated that it remains confident in the potential of tabelecleucel to provide meaningful benefit to patients with post-transplant lymphoproliferative disease and looks forward to working with the FDA’s current review team, alongside its partners, to address the concerns raised.
References
Atara Biotherapeutics Provides Regulatory and Business Update on EBVALLO™ (tabelecleucel), 12 January 2026, https://investors.atarabio.com/news-events/press-releases/detail/380/atara-biotherapeutics-provides-regulatory-and-business
Atara Biotherapeutics Provides Regulatory and Business Update on EBVALLO™ (tabelecleucel), 16 January 2025, https://investors.atarabio.com/news-events/press-releases/detail/367/atara-biotherapeutics-provides-regulatory-and-business
Atara Biotherapeutics Announces Third Quarter Financial Results and Operational Progress, 12 November 2025, https://investors.atarabio.com/news-events/press-releases/detail/379/atara-biotherapeutics-announces-third-quarter-financial