AtheroGenics Inc, a pharmaceutical company focused on the treatment of chronic inflammatory diseases, announced positive results from a Phase I clinical trial that assessed the safety and tolerability of its novel oral drug, AGI-1096, for the prevention of organ transplant rejection.
The Phase I trial was an open-label, ascending single dose, safety and pharmacokinetics trial in healthy volunteers. A total of 48 subjects received single doses of AGI-1096, ranging from 5 mg to 640 mg.
The results from this trial demonstrated that AGI-1096 was well tolerated over the escalating single oral doses studied. Adverse events were generally mild and not considered clinically significant. Subjects reached targeted plasma concentration levels for AGI-1096 that were based on those that resulted in efficacy in pre-clinical models of solid organ transplant rejection.
"We are very pleased with the encouraging results from this Phase I study in healthy volunteers," stated Russell M. Medford, President and Chief Executive Officer of AtheroGenics. "These results continue to bolster the enthusiasm we have for our pipeline of novel vascular protectant drug candidates. If successfully developed, AGI-1096 may potentially provide a unique complementary therapy to immunosuppressants currently being used to prevent organ transplant rejection."
AGI-1096 is a selective anti-inflammatory agent and antioxidant derived from AtheroGenics'' v-protectant technology platform. AGI-1096 represents a novel approach to treating transplant rejection in two ways- first, by diminishing the inflammatory response associated with the transplant and second, by protecting the blood vessels to the transplanted organ through its v-protectant activity.
Current therapy for transplant rejection involves utilizing a regimen of immunosuppressants, including cyclosporin A, tacrolimus, and rapamycin (sirolimus). However, the Scientific Registry of Transplant Rejection reports that, even with the use of immunosuppressants, patients have a 20 to 50 percent risk of rejecting a donated organ during the first three years following transplantation, and less than 50 percent of patients have functioning grafts after approximately 10 years. Additionally, chronic use of immunosuppressants can lead to impairment of the graft recipients'' immune system.
Organ transplantation takes place when an organ from a donor is surgically removed and placed into a recipient patient whose own organ has been destroyed by disease or infection. Nearly all transplant patients will experience one or more episodes of rejection during their recovery period. Chronic rejection occurs either because the organ recipient''s immune system, during the course of months or years, comes to recognize the transplant as "foreign", or because the blood supply to the transplant becomes blocked due to an accelerated closure (inflammation) of the blood vessels leading to the transplanted organ. Chronic rejection is a major factor contributing to today''s serious transplant organ shortage. Industry sources report there are over 200,000 organ transplant recipients in the United States who are at risk of chronic transplant rejection.