FDA Issues Complete Response Letter for Tabelecleucel for EBV-positive PTLD

The FDA has issued a Complete Response Letter (CRL) to Atara Biotherapeutics for the Biologics License Application (BLA) of tabelecleucel monotherapy for the treatment of adult and pediatric patients aged two years 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–containing regimen.¹

The CRL is related to observations of a third-party manufacturing facility as part of a standard prelicense inspection. The manufacturing process, clinical efficacy, and clinical safety of the drug were not identified as factors related to the CLR.¹

The BLA for tabelecleucel, an allogeneic, EBV-specific T-cell immunotherapy designed to target and eliminate EBV-infected cells, is supported by results of the ALLELE study published in The Lancet Oncology. In this phase III trial, tabelecleucel demonstrated a statistically significant objective response rate of 50%. The most common grade 3 or 4 treatment-related adverse events were disease progression (29%) and decreased neutrophil count (29%).²

“We are working closely with our partner Pierre Fabre Laboratories, the FDA, and the third-party manufacturer to address the feedback to support marketing approval for [tabelecleucel],” said Cokey Nguyen, PhD, President and Chief Executive Officer of Atara, in a press release. “Once the third-party manufacturer GMP compliance issues have been adequately addressed, we will file for a resubmission, which we would expect to be potentially approved within six months of resubmission.”

References

1. Atara Biotherapeutics Provides Regulatory and Business Update on EBVALLO™ (tabelecleucel). Atara Bio. January 16, 2025. Accessed January 17, 2025. https://investors.atarabio.com/news-events/press-releases/detail/367/atara-biotherapeutics-provides-regulatory-and-business
2. Mahadeo KS, Baiocchi R, Beitinjaneh A, et al. Tabelecleucel for allogeneic haematopoietic stem-cell or solid organ transplant recipients with Epstein-Barr virus-positive post-transplant lymphoproliferative disease after failure of rituximab or rituximab and chemotherapy (ALLELE): a phase 3, multicentre, open-label trial. Lancet Oncol. 2024;25(3):p376-387. doi:10.1016/S1470-2045(23)00649-6