All of Atara Biotherapeutics’ T-Cell Immunotherapy Trials Placed on Clinical Hold by the FDA

The FDA has placed clinical holds on Atara Biotherapeutics’active investigational new drug applications, which include clinical trials for tabelecleucel (tab-cel, also known as Ebvallo), an allogeneic Epstein-Barr virus (EBV)-specific T-cell immunotherapy under evaluation for patients with relapsed/refractory (r/r) EBV-positive post-transplant lymphoproliferative disease (EBV+ PTLD), and ATA3219, an investigational allogeneic CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy consisting of EBV-sensitized T-cells that have not been genetically modified being evaluated for nonHodgkin lymphoma (NHL) and systemic lupus erythematosus (SLE).¹

Clinical trials impacted include the phase 3 ALLELE clinical trial (NCT03394365) in EBV+ PTLD for tab-cel, a phase 1 clinical trial (NCT06429800) in SLE for ATA3219, and a phase 1 clinical trial (NCT06256484) in r/r B-cell NHL for ATA3219. The hold is related to a good manufacturing practice (GMP) compliance issue identified at a third-party manufacturer for tab-cel while the FDA was conducting a prelicense inspection forth product in relation to its biologics license application (BLA). Although ATA3219 is produced at a separate facility that is in full compliance with GMP, starting materials used in its production come from the aforementioned third-party manufacturer and are thus implicated.

“We intend to work closely with the FDA to address these issues as expeditiously as possible,” Cokey Nguyen, PhD, the president and chief executive officer of Atara, said in a statement.¹ “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 noted that treatment may continue to be administered in accordance with study protocol to certain specifically-identified patients who are already enrolled in the trials and who have been determined to have potential for clinical benefit, but that all screening and enrollment of new patients has been halted. The company also pointed out that the GMP compliance issue does not affect its other third-party manufacturer, a FUJIFILM Diosynth Biotechnologies facility in Thousand Oaks, California. Furthermore, Atara stated that it has come into alignment with the FDA in discussions on the necessary actions for resolution of the holds.

Notably, the compliance issue previously led the FDA to issue a complete response letter (CRL) to Atara regarding its BLA for tab-cel on January 16th, 2025.² The CRL was exclusively related to the GMP noncompliance issue at the third-party facility rather than to any concerns regarding the efficacy and safety data on the record for tab-cel, which in recent years has been approved in the Europe Union, the United Kingdom, and Switzerland for the treatment of r/r EBV+ PTLD in patients who have received at least 1 prior therapy.^2,3 The manufacturing process itself was not implicated, and the FDA did not request additional clinical trials for tab-cel.

“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 Ebvallo,” Nguyen said in a January 16 statement.² “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 6 months of resubmission. Atara and its partner Pierre Fabre remain confident in the potential of Ebvallo and are committed to bringing this potential first-in-class medicine to United States patients with EBV+ PTLD who have limited treatment options and significant unmet need.”

REFERENCES
1. Atara Biotherapeutics provides update on clinical programs related to Ebvallo (tabelecleucel) and ATA3219. News release. Atara Biotherapeutics, Inc. January 21, 2025. Accessed January 21, 2025. https://investors.atarabio.com/news-events/press-releases/detail/368/atara-biotherapeutics-provides-update-on-clinical-programs
2. Atara Biotherapeutics provides regulatory and business update on EBVALLO (tabelecleucel). News release. Atara Biotherapeutics, Inc. January 16, 2025. Accessed January 21, 2025. https://investors.atarabio.com/news-events/press-releases/detail/367/atara-biotherapeutics-provides-regulatory-and-business
3. Atara Biotherapeutics Submits Tabelecleucel (Tab-cel®) Biologics License Application for Treatment of Epstein-Barr Virus Positive Post-Transplant Lymphoproliferative Disease with U.S. FDA. News release. Atara Biotherapeutics. May 20, 2024. Accessed January 21, 2025. https://www.businesswire.com/news/home/20240520985176/en/Atara-Biotherapeutics-Submits-Tabelecleucel-Tab-cel%C2%AE-Biologics-License-Application-for-Treatment-of-Epstein-Barr-Virus-Positive-Post-Transplant-Lymphoproliferative-Disease-with-U.S.-FDA