Ebvallo, which Pierre Fabre Pharmaceuticals and Atara Biotherapeutics are proposing to treat a posttransplant complication, joins a wave of rejected or discouraged therapies on which the FDA has reversed previous guidance after the exit of former Commissioner Marty Makary.
Pierre Fabre Pharmaceuticals and Atara Biotherapeutics are taking another shot at getting their twice-rejected cell therapy Ebvallo across the regulatory finish line, announcing a new FDA submission for the candidate to treat a complication of organ transplants.
The resubmission for Ebvallo, also called tabelecleucel, is a “positive step” in terms of alignment with the FDA on a path forward for the cell therapy, Mizhuo analysts said in a note to investors Tuesday morning. “Given the additional data included in the resubmission, we believe it will most likely be a Class 2 BLA resubmission,” the firm added, meaning the asset could receive a target FDA action date of March 29, 2027.
First rejected as a treatment for patients 2 years and older with Epstein-Barr virus-positive posttransplant lymphoproliferative disease (EBV+ PTLD)—a rare, potentially life-threatening condition that can occur after solid organ transplant—Ebvallo was hit with a second complete response letter (CRL) in January this year.
While the first rejection was “solely related to inspection findings at third-party manufacturer,” according to Atara’s January 2025 announcement, the FDA in its second CRL a year later told the partners that the single-arm, pivotal Phase 3 ALLELE study was insufficient to support the biologics license application (BLA)—despite previously saying that it was, according to Atara at the time. The FDA said that the trial’s interpretability was confounded due to trial study design, conduct and analysis, Atara said. The regulator further confirmed that the GMP compliance issues had been satisfactorily resolved, and no safety issues were raised.
“The FDA’s new position is contrary to the FDA’s prior guidance to Atara, the FDA’s alignment with Atara on the clinical trial data set, and the acceptance of the trial design as a single arm study as relevant for this patient population at BLA submission,” the company said in a Jan. 12 press release, adding that this prior alignment had been reached through “multiple, documented meetings held over the past five plus years.”
Claims such as these were echoed by several biotechs—particularly those focused on rare disease—during Marty Makary’s tenure as FDA commissioner. Disgruntled companies included uniQure, REGENXBIO, Biohaven and Capricor Therapeutics. Shortly after the departures of Makary and former Center for Biologics Evaluation and Research (CBER) Director Vinay Prasad this spring, however, some of these biotechs were told that their current data were sufficient after all. UniQure, for example, filed regulatory applications with both the FDA and the U.K.’s Medicines and Healthcare products Regulatory Agency earlier this month after delaying on the FDA’s advice late last year.
Similarly, the FDA appeared to reverse course on Ebvallo again in May, agreeing that a single-arm study “using an appropriate historical control applicable to the trial population” may serve as an “adequate and well controlled study” to support Atara and Pierre Fabre’s application.
Despite the FDA’s apparent change of mind, Atara and Pierre Fabre are buttressing their application with an updated data package including additional patients and longer follow up from ALLELE. The resubmission also includes “additional supplemental data from the expanded access programs, a separate clinical study, and commercial experience in Europe,” Atara said on Wednesday.
The partners will now await acceptance of their application and a new FDA action date.
“We are grateful to the Agency for their continued guidance and engagement with our partner, PFP, and us,” Atara CEO Cokey Nguyen said in a prepared statement on Wednesday. “We will continue to support PFP as it prepares for the review process and anticipate providing a revised anticipated PDUFA date as it becomes available.”
Under their commercialization agreement, struck in November 2023, Atara is eligible to collect a $31 million milestone payment upon Ebvallo’s FDA approval.
