Tabelecleucel

“We are concerned that this decision may have far-reaching consequences for the development of rare disease treatments," Pierre Fabre Pharmaceuticals said in a Jan. 12 statement on the FDA's rejection. With Ebvallo’s latest U.S. rejection in Epstein-Barr virus positive post-transplant lymphoproliferative disease (EBV+PTLD)—a condition the drug has been approved to treat in Europe since late 2022—Atara Biotherapeutics and its partner Pierre Fabre Pharmaceuticals are accusing the FDA of pulling an about-face.The FDA has issued a complete response letter for the partners’ application in EBV+PTLD, marking the agency’s second snub of Ebvallo (tabelecleucel) following a rejection in early 2025 tied to issues at a third-party manufacturer, Atara reported Monday.Atara and Pierre Fabre, which took on U.S. rights to the drug in 2023, were hoping to win U.S. approval for Ebvallo monotherapy in adult and pediatric patients with EBV+PTLD who’ve received at least one prior treatment, including an anti-CD20 regimen. Ebvallo scored a thumbs up in a similar indication covering patients ages 2 years and older in the European Union in Dec. 2022. The drug has also won endorsements in countries such as Switzerland.Despite the medicine’s success with regulators overseas, Ebvallo was rebuffed by the FDA last January in a response letter “solely related to inspection findings” at an unnamed contract manufacturer, Atara said at the time.In what is no doubt a frustrating turn of events for Atara and Pierre Fabre, who resubmitted their US Ebvallo application last year “after reaching alignment with the FDA,” the regulator acknowledged in its latest CRL that the partners had resolved the production compliance issues but rejected the drug on entirely new grounds.Namely, in what Atara branded “a complete reversal of position,” the FDA has now asserted that Ebvallo’s single-arm Allele trial—which the agency previously signed off on—is “no longer considered to be adequate to provide evidence of effectiveness for accelerated approval,” the company said Monday.“Furthermore, the FDA stated that the trial’s interpretability is confounded due to trial study design, conduct, and analysis,” Atara continued. Atara criticized the FDA’s apparent pivot, noting that the regulator’s new point of view runs “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” at the time it resubmitted its application.The company noted that it had come to a previous understanding with the agency through “multiple, documented meetings held over the past five plus years.”In a separate statement, Pierre Fabre Pharmaceuticals channeled further frustrations in the FDA’s direction.Pierre Fabre first joined forces with Atara on Ebvallo in Oct. 2021 under a commercialization agreement spanning Europe, the Middle East, Africa and certain other markets. Pierre Fabre took on the drug’s U.S. rights in a deal potentially worth up to $640 million in 2023. More recently, in November, Atara transferred Ebvallo’s U.S. application to Pierre Fabre Pharmaceuticals, the U.S. subsidiary of Pierre Fabre Laboratories, the company noted in its release.“We are surprised and deeply disappointed by the FDA’s decision, particularly given the urgent and life-threatening unmet medical need faced by patients with [EBV+ PTLD] after failure of standard-of-care therapy,” the Pierre Fabre unit said Monday. “These patients have no FDA-approved treatment options and a life expectancy often measured in weeks to months.”“We are concerned that this decision may have far-reaching consequences for the development of rare disease treatments, effectively creating barriers for generating clinical evidence within a unique patient population with ultra-rare conditions, thereby significantly delaying—or preventing altogether—patient access to urgently needed therapies,” the Pierre Fabre statement continued.The comments come amid broader industry concerns of perceived instability at the FDA, with the agency enduring mass layoffs, major leadership departures and myriad review timeline delays in 2025.Back in November, hundreds of industry leaders penned a letter to FDA commissioner Marty Makary, M.D., stressing the importance of predictability at the U.S. regulatory body. The leaders highlighted persistent gaps in institutional memory and accountability at the agency, "where alignment no longer guarantees a stable regulatory framework for drug development." Meanwhile, the Ebvallo case isn’t the first drug review for which the FDA has made an apparent U-turn in recent months.Late last year, the FDA determined that data from a phase 1/2 study of uniQure’s experimental gene therapy AMT-130 were no longer sufficient to support an approval application in Huntington’s disease, according to a November announcement from the company. The pivot came after the FDA and uniQure aligned in 2024 on a submission under the agency’s accelerated approval pathway, which was based on data from the phase 1/2 study.At the time, uniQure’s CEO expressed surprise at the FDA’s “drastic change from the guidance” it previously provided.Regarding next steps for Ebvallo, Pierre Fabre will request a Type A meeting with the FDA, which it expects to be granted within 45 days. The partners aim to “urgently interact with the FDA to find a path forward for the timely accelerated approval” of their drug, Atara said Monday. For its part, Atara met with a cascade of problems last year following its initial Ebvallo rejection in the U.S.Shortly after announcing the FDA’s 2025 snub, Atara revealed that the agency had placed a clinical hold on the company’s applications for both Ebvallo in EBV+PTLD and an allogeneic CD19-targeted CAR-T candidate for non-Hodgkin lymphoma, which prompted the drugmaker to lay off roughly half of its workforce in March.While the FDA ultimately released the hold on Ebvallo in early May, the company nevertheless announced plans to reduce its remaining headcount by another 30% that same month. At the time, the second downsizing move left just 23 employees at the biopharma, who the company said were “essential” to executing on its strategic priorities.