Transplantation has advanced since the 1980's to become a relatively common and cost-effective procedure. However, acute rejection of a substantial proportion of organ transplants, as well as widespread chronic rejection of organ transplants, are still significant medical challenges. Clinical investigators and laboratory scientists have identified that there may be a significant role of antibody/complement-mediated rejection both in the acute rejection and chronic rejection processes.

Acute Antibody/Complement-Mediated Transplantation Rejection

Approximately 25,000 people received whole organ transplants in the United States in 2002, but there are currently over 80,000 patients on the waiting list for organ transplantation. Most current anti-rejection medications target T-cell mediated rejection. However, many potential organ recipients have antibodies that react with the donor organ and lead to severe, acute post-transplantation rejection episodes; an even greater number of potential transplant recipients, including many both on the waitlist and also those not listed on the waitlist, are prevented from being offered an organ transplant because of the presence of high levels of these rejection-mediating antibodies in the prospective transplant recipients prior to transplantation. The organ recipient's antibodies bind to the donated organ tissue, leading to the subsequent activation of complement. This complement activation rapidly causes inflammation and destruction of the transplanted organ. Patients may be treated with plasmapheresis (a procedure where proteins are removed from the blood) for 20-100 episodes before and after transplantation in order to attempt to mitigate the severe organ rejection. Despite these extensive and costly procedures, current therapies are not sufficient to prevent antibody-mediated rejection.

C5 Inhibitor Therapy in Models of Transplantation

In collaboration with investigators at the Multi-Organ Transplant Program, London Health Sciences Centre, London, Ontario, Canada, Alexion scientists reported in the May 2005 issue of the journal Transplantation that inhibition of terminal complement using an anti-C5 complement-blocking antibody successfully prevented AMR in a rodent model of transplantation. Furthermore, addition of anti-C5 antibody to standard anti-cellular therapy resulted in a marked and significant increase in graft survival as compared to graft survival in animals treated with anti-cellular therapy alone. Importantly, AMR was prevented by anti-C5 antibody even in the presence of high levels of circulating anti-donor antibodies.

Healthcare costs

Alexion believes that more effective transplantation therapy, with eculizumab, may provide significant cost savings to the healthcare system, by reducing the need to utilize other more expensive and less effective therapies. An example of some of the potential pharmacoeconomic benefits can be seen in patients with end-stage renal (kidney) disease. The cost per quality-adjusted life year for kidney transplantation was found to be 75 percent less than the cost for dialysis. Overall, it has been estimated that broader implementation of renal transplantation alone, instead of dialysis, could save the Federal government as much as $2 billion annually.