Study in Today's New England Journal of Medicine Suggests Benefits of Genzyme’s Thymoglobulin Sustained Through Five Years in Kidney Transplant Patients
Novel Technique Linking Clinical Trial and Transplant Registry Data
Allows Long-term Follow up
CAMBRIDGE, Mass. October 16, 2008 - Genzyme Corporation announced today that the New England Journal of Medicine published a Letter highlighting the long-term five-year outcomes of a randomized multinational study of kidney transplant patients undergoing induction therapy with Thymoglobulin® (Anti-thymocyte globulin [Rabbit]) or basiliximab. This novel analysis used an innovative technique of linking clinical trial data to transplant registry data to obtain the long- term results.
In the U.S., Thymoglobulin is indicated for the treatment of acute renal graft rejection in conjunction with concomitant immunosuppression. This study examined the use of Thymoglobulin for the prevention of acute renal graft rejection (induction), which is not an approved indication in the U.S.
By employing a novel data-collection technique of linking trial and registry data, long-term outcomes, beyond the original scope of the trial, were obtained. At 5 years, the incidence of acute rejection (16.0% versus 30.0%; P=0.03), the need for antibody treatment of acute rejection (3.3% versus 12.0%. P=0.05), and the composite endpoint of acute rejection, graft loss, and death (38.8% versus 52.0%, P=0.04) were all lower among patients treated with Thymoglobulin compared to basiliximab. Importantly, this study confirmed that the incidence of treated cytomegalovirus infection remained lower in the Thymoglobulin group (6.6% versus 17.4%, P=0.04) and the incidences of post-transplant malignancy were low and equivalent among treatment groups through 5 years.
"This study showed that Thymoglobulin had a long-lasting, beneficial and durable effect." said Daniel C. Brennan, M.D., director of transplant nephrology, Washington University School of Medicine. "Further, the methodology we used could be used to discover the long-term outcomes of any study in kidney transplant patients in the U.S. and could be extrapolated to other fields where there are registry data available."
Thymoglobulin is an immunosuppressive product that contains antibodies directed against antigens expressed on human lymphocytes. Possible mechanisms by which Thymoglobulin may induce immunosuppression in vivo include: T-cell clearance from the circulation, alteration of T-cell activation, modulation of leukocyte-endothelium interactions, depletion of B cell lineages, and expansion of T regulatory cells.
About the Study
Currently over 78% of kidney transplant patients in the United States receive antibody induction therapy. This study compared the long-term safety and efficacy of two of the most commonly used induction agents, Thymoglobulin and basiliximab, in patients who received a renal allograft from a deceased donor and were at high risk of acute rejection or delayed graft function. As participants in the original prospective clinical trial, all patients were randomly assigned to receive either Thymoglobulin or basiliximab at the time of transplant in a 1:1 ratio. Both groups received maintenance immunosuppressive therapy involving cyclosporine modified, mycophenolate mofetil and prednisone.
One-year results from the original trial were previously published in the New England Journal of Medicine in 2006. After the initial 12-month follow-up period, records from US-enrolled patients in the trial (n=183) were uniquely matched to their corresponding records in the Organ Procurement and Transplantation Network (OPTN) registry based on demographic and transplant-related variables. All matches were verified using blood groups and human leukocyte antigens of each donor and recipient. Long-term outcomes obtained from the OPTN registry showed that the safety profile and benefits of Thymoglobulin over basiliximab were sustained through 5 years post transplant.
About Renal Transplant
According to the National Kidney Foundation, there were 16,626 kidney transplants and 862 combination kidney and pancreas transplants in the United States in 2007. Of the single kidney transplants that year, 6,039 were from living donors and 10,587 were from deceased donors.
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. Thymoglobulin is contraindicated in patients with a history of allergy or anaphylaxis to rabbit proteins or to any product excipients, or who have active acute or chronic infections which contraindicate any additional immunosuppression. Serious immune-mediated reactions have been reported with the use of Thymoglobulin and consist of anaphylaxis or severe cytokine release syndrome (CRS). Fatal anaphylaxis has been reported. Severe, acute infusion-associated reactions (IARs) are consistent with CRS and can cause serious cardiorespiratory events and/or death. IARs may occur as soon as the first or second infusion during a single course of Thymoglobulin treatment. During post-marketing surveillance, fever, rash, arthralgia and/or myalgia have been reported to occur 5 to 15 days after onset of Thymoglobulin therapy, indicating possible serum sickness. These symptoms are manageable with corticosteroid treatment. Infections, reactivation of infection, sepsis, malignancies including post-transplant lymphoproliferative disorder (PTLD) and other lymphomas as well as solid tumors have been reported after Thymoglobulin administration in combination with multiple immunosuppressive agents.
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, infection, dyspnea, asthenia, hyperkalemia and tachycardia.
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 http://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. Since 1981, the company has grown from a small start-up to a diversified enterprise with more than 10,000 employees in locations spanning the globe and 2007 revenues of $3.8 billion. In 2007, Genzyme was chosen to receive the National Medal of Technology, the highest honor awarded by the President of the United States for technological innovation.
With many established products and services helping patients in nearly 90 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, orthopaedics, cancer, transplant and immune disease, and diagnostic testing. Genzyme's commitment to innovation continues today with a substantial development program focused on these fields, as well as cardiovascular disease, neurodegenerative diseases, and other areas of unmet medical need.
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Posted: October 2008