Following the surprise rejection in early 2026, the FDA agreed to reconsider the T-cell therapy based on the same single-arm trials it had previously found problematic.
For Pierre Fabre Pharmaceuticals and Atala Biotherapeutics’ Evalo, the FDA agreed in a recent meeting that a single-arm study with appropriate historical controls “may serve as an appropriate, well-controlled study” to support a regulatory filing, the companies announced Thursday.
Pierre Fabre and Atala aim to get Evalo, also known as Tabelleklucel or Tabcel, approved for patients with relapsed or refractory Epstein-Barr virus-positive post-transplant lymphoproliferative disease (EBV+PTLD) who have failed anti-CD20 therapy. Before the FDA, European regulators had already given the green light for immunotherapy for a 2022 indication.
When the FDA refused to approve Evalo in January, it said the same single-arm study conducted by the pair was “not an adequate, well-controlled study” and had numerous flaws that made the results uninterpretable. Atallah at the time called the FDA’s surprise ruling a “complete reversal of position” and “contrary to” the agency’s previous communications and collaboration with the company.
Now, instead of running separate trials, the companies plan to resubmit Ebvallo with additional patients and long-term follow-up in a single-arm trial called Allele.
Adriana Herrera, CEO of Pierre Fabre’s U.S. subsidiary, said in a May 7 statement: “We would like to thank the FDA review team for productive discussions regarding the Tabelle Cloucel BLA and look forward to finalizing our resubmission plans with the FDA in the coming weeks.” “Patients in the United States living with this ultra-rare form of lymphoma are in urgent need of FDA-approved treatment options, as currently no FDA-approved treatment options exist. Additionally, life expectancy for R/R EBV+ PTLD patients is often measured in weeks to months after standard treatments have failed.”
EBV+ PTLD is an extremely rare and aggressive blood cancer that occurs when EBV reactivation causes uncontrolled proliferation of B cells in patients who have received immunosuppressants for stem cell or solid organ transplantation. Only a few hundred patients are affected by EBV+ PTLD each year.
Ebvallo is an off-the-shelf immunotherapy consisting of EBV-specific cytotoxic T cells from healthy EBV-seropositive donors aimed at eliminating EBV-expressing cells.
Ebvallo is regulated as a cell therapy by the FDA’s Center for Biologics Evaluation and Research (CBER). Dr. Vinay Prasad, the hematologist who oversaw the FDA division at the time of Evvaro’s rejection in January, left the agency at the end of April.
Evalo was one of several rare disease candidates to stumble at the FDA as the agency took issue with some single-arm natural history studies, even as Marty McCurry, MD, touted regulatory flexibility for orphan drugs.
One of the most high-profile cases was the FDA’s rejection of uniQure’s single-arm study compared to natural history data as the basis for its application for Huntington’s disease gene therapy AMT-130, which also falls under CBER. As uniQure argues for a change in direction, the FDA maintains that randomized, sham-controlled Phase 3 trials have always been the agency’s recommendation.
UniQure is embarking on its own meeting with the FDA following a very public controversy. And the Evaro incident could reignite investor expectations for a possible reversal in AMT-130.
Related: FDA officials confirm plausible mechanistic principles not limited to tailored gene therapy
During the company’s first-quarter earnings call on Tuesday, UniQure’s chief medical officer, Walid Abisaab, M.D., said the upcoming discussions with the FDA are “technical meetings” rather than a reassessment of the agency’s position.
“Our hope is to gain some clarity on the key design elements of additional new studies to evaluate the efficacy of AMT-130 and to receive feedback on the planned statistical analysis of the four-year data,” Abiserv said on the conference call, later adding, “We do not intend to have any specific discussions about the regulatory path toward filing at this time.”
Nevertheless, analysts at Leerink Partners believe that if uniQure produces convincing four-year data, the meeting could be an “opportunity to evolve the FDA’s stance.”
UniQure plans to meet with the FDA this quarter and report four-year results from its existing clinical trial for AMT-130 in the third quarter.
