Study in Today’s New England Journal of Medicine Shows Benefits of Thymoglobulin Use
Treatment Reduced Risk of Acute Rejection Among High Risk Kidney Transplant Patients
November 9, 2006 - Genzyme Corporation (Nasdaq: GENZ) announced today that the New England Journal of Medicine published the results of a randomized multinational study comparing the outcomes of kidney transplant patients undergoing induction therapy with Thymoglobulin® (Anti-thymocyte globulin [Rabbit]) with those receiving induction therapy with basiliximab.
Results of the study, Rabbit Antithymocyte Globulin versus Basiliximab for Induction in Renal Transplantation, showed that treatment with Thymoglobulin resulted in a significantly reduced risk of acute rejection and acute rejection requiring antibody therapy, and a similar risk of delayed graft function, graft loss and death. The study involved 278 patients at high risk for acute rejection or delayed graft function following a kidney transplant from a deceased donor. The primary endpoint of the study was a composite measure of the first occurrence of four factors: acute rejection, delayed graft function, graft loss and death. At 12 months, the incidence of the composite end point was similar in the two groups (50.4% for the Thymoglobulin group versus 56.2% for the basiliximab group; P=0.34).
The Thymoglobulin group, as compared with the basiliximab group, had a 38.8% lower incidence of acute rejection (15.6% versus 25.5%, P=0.02) and a 82.5% lower incidence of severe acute rejection that required treatment with antibody (1.4% versus 8.0%, P=0.005).
“Our study showed the risk of acute rejection was about 1.5 times higher among patients treated with basiliximab, and the need for antibody treatment related to acute rejection was six times higher among the basiliximab group,” said Daniel C. Brennan, M.D., director of transplant nephrology, Washington University School of Medicine. “These results are an important contribution to our understanding of these treatment approaches, and we look forward to examining the longer term outcomes of these patients.”
Genzyme Corporation, sponsor of the study, markets Thymoglobulin in more than 50 countries around the world. In the United States, Thymoglobulin is indicated for the treatment of acute renal graft rejection in conjunction with concomitant immunosuppression. In many countries worldwide, Thymoglobulin is also indicated for the prevention of acute renal graft rejection (induction), the use examined in this study. In the United States, Thymoglobulin is not indicated for the prevention of acute renal graft rejection.
Thymoglobulin is an immunosuppressive product that contains cytotoxic antibodies directed against antigens expressed on human T-lymphocytes. Possible mechanisms by which Thymoglobulin may induce immunosuppression in vivo include: T-cell clearance from the circulation and modulation of T-cell activation, homing, and cytotoxic activities.
About the Study
Currently about 70% of kidney transplant patients in the United States receive antibody induction therapy. This study compared the safety and efficacy of two of the most commonly used treatment options for induction therapy, basiliximab and Thymoglobulin. Treatment was administered intraoperatively and over four days following transplantation among patients who received a renal allograft from a deceased donor and were at high risk of acute rejection or delayed graft function. All patients were randomly assigned to receive either Thymoglobulin or basiliximab in a 1:1 ratio. Patients were followed for 12 months.
In the study, researchers compared short courses of treatment with either Thymoglobulin or basiliximab. Treatment with Thymoglobulin was initiated intraoperatively, before graft reperfusion. Subsequent doses were given daily through post-operative day four for a total dose of 7.5 mg per kilogram. Treatment with basiliximab at 20 mg was administered intravenously according to manufacturer’s instructions, with a first infusion before graft reperfusion and a second infusion on post-operative day four. Both groups received maintenance immunosuppressive therapy involving cyclosporine modified, mycophenolate mofetil, and prednisone.
In addition to the benefits seen for the Thymoglobulin group in reducing the incidence of acute rejection and antibody treatment for acute rejection, the study also showed that the incidences of delayed graft function and graft loss were statistically similar in both groups. As anticipated, the Thymoglobulin group experienced a higher initial incidence of leukopenia and thrombocytopenia immediately after transplantation, but by day 14 post-transplant there were no significant differences noted between the treatment groups. While the incidence of adverse events, serious adverse events and cancer were similar in both groups, patients treated with Thymoglobulin had a higher incidence of infection (85.5% versus 75.2%, P=0.03) but a lower incidence of cytomegalovirus disease (7.8% versus 17.5%, P=0.02).
About Renal Transplant
According to the National Kidney Foundation, there were 16,004 kidney transplants and 881 combination kidney and pancreas transplants in the United States in 2004. Of the single kidney transplants that year, 6,647 were from living donors and 9,357 were from cadaveric donors. According to the American Association of Kidney Patients, using current standard of care therapy, rejection rates for kidney transplants are estimated at 10-15%.
Important U.S. Safety Information:
WARNING: Thymoglobulin® should only be used by physicians experienced in immunosuppressive therapy for the management of renal transplant patients.
Thymoglobulin is indicated for the treatment of renal transplant acute rejection in conjunction with concomitant immunosuppression.
Medical surveillance is required during Thymoglobulin infusion. Patients with a history of allergy or anaphylaxis to rabbit proteins, or with an acute viral illness should not use Thymoglobulin. In rare instances, anaphylaxis has been reported. Thymoglobulin adverse events are generally manageable or reversible. The most frequent reported adverse events (more than 25% of patients) include: fever, chills, leukopenia, pain, headache, abdominal pain, diarrhea, hypertension, nausea, thrombocytopenia, peripheral edema, dyspnea, asthenia, hyperkalemia, tachycardia, and infection.
Prolonged use or overdose of Thymoglobulin in association with other immunosuppressive agents may cause over-immunosuppression. During Thymoglobulin therapy, monitoring the lymphocyte count may help assess the degree of T-cell depletion. WBC and platelet counts should also be monitored.
For more information on Thymoglobulin, please see full prescribing information available at www.thymoglobulin.com.
One of the world’s leading biotechnology companies, Genzyme is dedicated to making a major positive impact on the lives of people with serious diseases. This year marks the 25th anniversary of Genzyme’s founding. Since 1981, the company has grown from a small start-up to a diversified enterprise with more than 8,500 employees in locations spanning the globe and 2005 revenues of $2.7 billion. Genzyme has been selected by FORTUNE as one of the “100 Best Companies to Work for” in the United States.
With many established products and services helping patients in more than 80 countries, Genzyme is a leader in the effort to develop and apply the most advanced technologies in the life sciences. The company’s products and services are focused on rare inherited disorders, kidney disease, orthopedics, cancer, transplant and immune diseases, and diagnostic testing. Genzyme’s commitment to innovation continues today with a substantial development program focused on these fields, as well as heart disease and other areas of unmet medical need.
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