The U.S. Food and Drug Administration (FDA) has placed a clinical hold on Atara Biotherapeutics' active Investigational New Drug (IND) applications, impacting the EBVALLO (tabelecleucel) program for Epstein-Barr virus-positive post-transplant lymphoproliferative disease (EBV+ PTLD) and ATA3219, a CAR-T therapy for non-Hodgkin’s lymphoma and systemic lupus erythematosus. The hold, effective January 21, 2025, stems from inadequately addressed Good Manufacturing Practice (GMP) compliance issues at a third-party manufacturing facility. While patients currently enrolled in studies who may derive clinical benefit can continue treatment, screening and enrollment of new participants have been paused.
The clinical hold for EBVALLO is directly linked to GMP compliance issues identified during the pre-license inspection of the third-party manufacturing facility, as referenced in the Complete Response Letter (CRL) issued for EBVALLO on January 16, 2025. Although ATA3219 is manufactured at a separate, fully compliant GMP-certified facility, the starting materials used in its production are affected by the compliance issues at the same third-party facility referenced in the CRL.
These manufacturing issues are specific to the referenced third-party manufacturing facility and do not affect Atara’s second third-party manufacturer, FUJIFILM Diosynth Biotechnologies (FDB) facility in Thousand Oaks, California. The FDB facility remains a critical component of Atara’s long-term manufacturing strategy for both assets. Atara and the FDA have discussed and agreed upon the actions necessary to release the clinical holds, with the FDA confirming its commitment to working collaboratively and expeditiously with Atara to resolve the issues.
EBVALLO (tabelecleucel) for EBV+ PTLD
EBVALLO, already approved in Europe for EBV+ PTLD, is an allogeneic, EBV-specific T-cell immunotherapy designed to target and eliminate EBV-infected cells. The Biologics License Application (BLA) submitted to the FDA was based on results from the pivotal ALLELE study, which demonstrated a statistically significant 50% Objective Response Rate (ORR) and a favorable safety profile. The Complete Response Letter (CRL) received by Atara did not identify any deficiencies related to the manufacturing process, clinical efficacy, or clinical safety data in the BLA, and the FDA did not request any new clinical trials to support the approval of EBVALLO.
ATA3219 for Non-Hodgkin’s Lymphoma and Systemic Lupus Erythematosus
ATA3219 is an allogeneic CD19-targeted CAR-T therapy being developed for the treatment of non-Hodgkin’s lymphoma and systemic lupus erythematosus. The clinical hold impacts ongoing trials for this therapy, pausing the screening and enrollment of new participants. However, patients currently enrolled in the clinical studies who have the potential to derive clinical benefit may continue to receive treatment in accordance with the ongoing study protocols.
Company Response and Strategic Alternatives
"We intend to work closely with the FDA to address these issues as expeditiously as possible," said Cokey Nguyen, Ph.D., President and Chief Executive Officer of Atara. "We are encouraged with ongoing correspondence with the Agency and a potential path to submitting the necessary data to release the clinical hold. Patient safety remains our priority and maintaining the highest standards for our programs."
Atara has engaged a financial advisor to support the assessment of opportunities to advance and realize value from Atara’s CAR-T assets. If a strategic resolution is not reached to provide funding for its CAR-T development programs in the first quarter of 2025, Atara plans to suspend all CAR-T activities and significantly reduce company expenses and activities to only those that support the approval of EBVALLO, including through a near-term progressive transfer of all operational activities related to EBVALLO to Pierre Fabre. Atara has entered into a non-binding term sheet with Redmile Group to provide up to $15 million in funding through an equity line of credit.
Atara remains eligible to receive a $60 million milestone payment from Pierre Fabre upon FDA approval of the EBVALLO BLA, as well as significant double-digit tiered royalties as a percentage of net sales and milestones related to EBVALLO’s commercial sales.
