Breakthrough Therapy Designation for EBV-Associated Lymphoproliferative Disease After HCT

The US Food and Drug Administration (FDA) is giving the green light to a new immunotherapy for patients who have rituximab-refractory, Epstein-Barr virus-associated lymphoproliferative disease (EBV-LPD) following allogeneic hematopoietic cell transplantation (HCT). This new therapy uses cytotoxic T-lymphocytes (CTL) activated against the Epstein-Barr virus in the treatment of rituximab-refractory patients with EBV-LPD after HCT. 

The therapy is being developed through collaboration between Atara Biotherapeutics, Inc. and Memorial Sloan Kettering Cancer Center (MSKCC) in New York.  On March 2, 2015, the therapy was granted breakthrough therapy designation by the FDA.  To qualify for this designation, a drug must show credible evidence of a substantial improvement on a clinically significant endpoint over available therapies or over placebo if there is no available therapy, or in a study that compares the new treatment plus standard of care to the standard of care alone.  

EBV-CTL may provide an “off-the-shelf”, allogeneic, cellular therapeutic option for patients with EBV-LPD.  They are derived from T-cells collected from third-party plasma donors.  Once collected, the T-cells are exposed to specific antigens. The resulting activated T-cells are expanded, characterized, and stored for future therapeutic use in appropriate partially human leukocyte antigen (HLA)-matched patients. In the context of EBV-LPD, the EBV-CTL seeks out the cancer cells expressing EBV and destroys them. 

Breakthrough therapy designation for EBV-CTL was based on data from two separate clinical trials of EBV-CTL conducted by MSKCC. Data from these studies have been submitted for presentation at an upcoming medical conference in 2015.  Chair of the Department of Pediatrics and Chief of the Pediatric Bone Marrow Transplant Service at MSKCC, Richard J. O’Reilly, MD, said the receipt of breakthrough therapy designation brings the researchers one step closer to their ultimate goal of making EBV-CTL available to all patients with EBV-LPD.  He noted these patients have limited treatment options and suffer significant morbidity. This new FDA designation confers several benefits, including intensive FDA guidance and discussion, and eligibility for submission of a rolling biologic license application.

President and Chief Executive Officer of Atara, Isaac Ciechanover, MD, said the designation underscores an urgent need to bring novel treatments to patients with EBV-LPD after HCT.   He noted this off-the-shelf, adoptive T-cell therapy has the potential to be an important option for patients for whom there are no approved treatments.

References:

• Nasdaq GlobeNewswire. (2015). FDA Grants Breakthrough Therapy Designation to Epstein-Barr Virus (EBV) Targeted T-Cells for Treatment of EBV-Associated Lymphoproliferative Disease.