EBV+ PTLD The U.S. Food and Drug Administration has declined to approve Atara Biotherapeutics’ cell therapy tabelecleucel for a rare blood cancer, the company said on Monday, a decision that sent its shares down 56% in early trading. The agency issued a complete response letter stating that the application could not be approved in its current form.
According to Atara, the FDA said it was unable to approve the application because the single-arm Allele clinical trial, which had previously been confirmed by the agency as adequate to support a marketing application, was no longer considered sufficient to provide evidence of effectiveness for an accelerated approval. The regulator also stated that the trial’s interpretability was confounded due to issues related to its design, conduct, and analysis.
The latest decision follows an earlier rejection of the therapy in the United States. In early 2025, the FDA declined to approve tabelecleucel based on observations made during an inspection of a third-party manufacturing facility. Atara said the production compliance issues cited at that time had since been resolved, and the FDA acknowledged this in its most recent review, but rejected the therapy on new grounds related to clinical evidence.
Atara said the FDA’s current stance runs counter to its prior guidance. The company stated that the agency had previously accepted the Allele trial design and had confirmed that the data generated by the study were adequate to support the application. Atara added that this understanding was reached through multiple documented meetings with the FDA held over more than five years.
Tabelecleucel is a CAR-T cell immunotherapy designed to eliminate Epstein-Barr virus–infected cells. Atara sought U.S. approval for the therapy in adult and pediatric patients with Epstein-Barr virus–positive post-transplant lymphoproliferative disease, a rare and often fatal blood cancer that can develop following organ or stem cell transplantation.
There are currently no FDA-approved treatments for this condition in the United States. Physicians commonly recommend chemotherapy alone or in combination with other cancer therapies, such as rituximab, and surgery in rare cases.
The therapy has been approved in Europe since December 2022 under the brand name Ebvallo, including authorization for patients aged two years and older. It has also received endorsements from regulators in countries such as Switzerland.
Pierre Fabre Pharmaceuticals, Atara’s partner on the therapy, said the FDA’s decision contradicted extensive discussions with the agency over several years and warned of broader implications for rare disease drug development. In a statement, the company said the decision “may have far-reaching consequences for the development of rare disease treatments.”
Pierre Fabre added that patients with EBV+ PTLD in the United States have no approved treatment options and that their life expectancy is often measured in weeks to months after standard-of-care therapies fail.
Pierre Fabre plans to request a Type A meeting with the FDA, which it expects to be granted within 45 days, to urgently discuss a potential path forward for accelerated approval of the therapy. Atara said the companies intend to continue engaging with the agency following the issuance of the complete response letter
Regulatory Concerns Highlight Challenges for EBV+ PTLD Cell Therapies
The FDA’s decision to decline U.S. approval of Atara Biotherapeutics’ treatment highlights the regulatory complexity surrounding advanced cell therapies for EBV+ PTLD. While the therapy showed promise in addressing an unmet need for patients with EBV+ PTLD, the agency emphasized the importance of consistent manufacturing processes and comprehensive clinical data. These requirements are critical to ensuring long-term safety and effectiveness for individuals affected by EBV+ PTLD, particularly transplant recipients with weakened immune systems. The outcome underscores the rigorous standards cell therapy developers must meet as they seek approval for innovative EBV+ PTLD treatments in the United States.
