FDA Rejects Atara's Tab-Cel a Second Time, Citing ALLELE Trial Design

The US Food and Drug Administration has issued a second complete response letter for tabelecleucel (tab-cel, Ebvallo), an off-the-shelf T-cell immunotherapy for a rare disease that can follow organ or stem cell transplants, Atara Biotherapeutics said on January 12, according to the company's announcement, filed with the SEC. The letter means the FDA cannot approve the biologics license application in its present form.

The application sought accelerated approval of tab-cel as a single treatment for adults and children aged two and older with Epstein-Barr virus-positive post-transplant lymphoproliferative disease (EBV+ PTLD) who have received at least one prior therapy, including an anti-CD20 regimen. Atara said it received the letter after market close on January 9.

Manufacturing resolved, trial questioned

The FDA's first complete response letter, dated January 15, 2025, identified a single deficiency in Good Manufacturing Practice compliance and raised no concerns about safety, efficacy or trial design, according to Atara. The company said the new letter confirmed the manufacturing issues had been satisfactorily resolved and raised no safety issues.

Instead, Atara said, the letter states that the single-arm ALLELE trial is no longer considered adequate to provide evidence of effectiveness for accelerated approval, and that the trial's interpretability is confounded by its design, conduct and analysis. Atara called this "a complete reversal of position by the FDA," saying the agency had previously confirmed the trial as adequate to support the filing in meetings held over more than five years. The account of the letter comes from the company.

ALLELE is a Phase 3 study, as reported by Targeted Oncology, which said the trial's pivotal data showed an objective response rate of 48.8% at the time the application was accepted for review. Tab-cel is already approved in Europe, the outlet noted.

"We are surprised and disappointed by this FDA decision for EBV+ PTLD patients who have a significant unmet need," said Cokey Nguyen, Atara's president and chief executive, in the release. He said Atara had aligned with the agency on accelerated approval followed by a post-marketing confirmatory study.

Next steps and finances

Atara transferred the application in November 2025 to Pierre Fabre Pharmaceuticals, the US subsidiary of its commercial partner Pierre Fabre Laboratories. Pierre Fabre intends to request a Type A meeting with the FDA and expects it to be granted within 45 days, Atara said.

The company also reported preliminary, unaudited cash, cash equivalents and short-term investments of about $8.5 million as of December 31, 2025. In December, Atara amended its agreement with Pierre Fabre Medicament, reducing the milestone payment due on US approval to $31 million in exchange for the right to a potential additional $15 million commercial milestone payment. Atara said it cut headcount by about 90% year over year in 2025 and moved substantially all tab-cel activities and costs to Pierre Fabre.