The Dutch company Xenikos B.V., which develops innovative immunotherapies for treating patients with severe immune disease and post-transplant rejection, announced today that the U.S. Food and Drug Administration (FDA) has approved an investigational new drug (IND) application to initiate a U.S.-based clinical Phase 3 registration trial in order to test the efficacy of T-Guard for treating steroid-refractory acute graft-versus-host disease (SR-aGVHD) in patients following allogeneic stem cell transplantation.<\/p>\n\n\n\n
This\nsingle-arm, multi-center Phase 3 trial (BMT CTN 1802) is designed to evaluate\nthe efficacy and safety of T-Guard in 47 patients who receive an allogeneic\nstem cell transplantation and subsequently develop SR-aGVHD. The primary\nendpoint of the study will be the complete response rate at day 28, and key\nsecondary endpoints will include the duration of complete response and overall\nsurvival rate at six months.<\/p>\n\n\n\n
“Receiving\nFDA approval to initiate our U.S. Phase 3 registration trial is a major\nmilestone for us, as it is the next step in advancing T-Guard towards the\nmarket,” says Dr. Ypke van Oosterhout, Chief Executive Officer of Xenikos.\n“Importantly, T-Guard can be administered as a single one-week treatment\nand was previously shown to promote swift restoration of the immune system,\npotentially reducing the risk of future infection and relapse. Effective\ntherapies for treating patients with SR-aGVHD are urgently needed, and we\nbelieve that T-Guard has the potential to be an important addition to the\nmedical arsenal available for treating patients with this devastating and\npotentially fatal condition.”<\/p>\n\n\n\n
The trial\nwill be conducted in the U.S. by the Blood and Marrow Transplant Clinical\nTrials Network (BMT CTN), funded by the National Heart, Lung, and Blood\nInstitute (NHLBI) and the National Cancer Institute (NCI), which are co-funding\nthe trial. Drawing on its vast network of leading transplant centers throughout\nthe U.S., the BMT CTN is expected to be able to quickly recruit patients for\nthe trial, thereby helping bring T-Guard to market as quickly as possible.<\/p>\n\n\n\n
Dr.\nGabrielle Meyers, Study Co-Chair, asserts, “The BMT CTN is the only U.S.\nclinical trial group focused on improving outcomes for transplant recipients.\nFor many years few studies were conducted for steroid-refractory GVHD due to\nthe difficulty in treating this challenging patient population. We are excited\nabout the opportunity to work with Xenikos to bring novel therapies to benefit\npatients in greatest need.”<\/p>\n\n\n\n
Study\nCo-Chair Dr. John Levine notes, “Steroid-refractory GVHD is the driver for\nnon-relapse deaths after allogeneic HSCT. Poor immune reconstitution and the\nresulting infections are major contributors to the high mortality. T-Guard’s\nnovel mechanism of action that preferentially targets activated T cells has\nshown rapid immune recovery and high response rates. This collaboration with\nthe BMT CTN will hopefully develop the confirmatory evidence needed to move T-\nGuard towards FDA approval.”<\/p>\n\n\n\n
T-Guard is designed to safely and swiftly reset the body’s immune system in life-threatening T cell\u2012mediated conditions, including transplant-related rejection, acute solid-organ rejection, and severe autoimmune disease. T-Guard consists of a unique combination of toxin-conjugated monoclonal antibodies that target CD3 and CD7 molecules on T cells and NK cells. Preclinical and early clinical testing have shown that T-Guard can specifically identify and eliminate mature T cells and NK cells with minimal treatment-related side effects. Importantly, T-Guard’s action is short-lived, thereby significantly reducing the patient’s vulnerability to opportunistic infections compared to currently available therapies. Xenikos successfully completed a Phase 1\/2 study for the second line treatment of SR-aGVHD in patients following hematopoietic stem cell transplantation (HSCT). The results of this study showed that just one week of T-Guard treatment triggered a strong clinical response and doubled the 6-month overall survival rate. These results were published in the peer-reviewed journal Biology of Blood and Marrow Transplantation. In addition to receiving IND clearance in the U.S., T-Guard has also been granted Orphan Drug Designation status in both the E.U. and the U.S.<\/p>\n\n\n\n