Sanofi has announced that the US Food and Drug Administration (FDA) approved Thymoglobulin [anti-thymocyte globulin (rabbit)], for use in conjunction with concomitant immunosuppression in the prophylaxis, or prevention, of acute rejection in patients receiving a kidney transplant.
Kidney disease is the ninth leading cause of death in the US; 468,000 patients are currently on dialysis for kidney failure, including an estimated 100,000 who are waiting for a kidney transplant. Kidney transplantation offers patients with end-stage renal disease longer survival and better quality of life compared to dialysis. With kidney transplantation, however, there is a risk of acute rejection, which can lead to graft complications and potential loss of the transplanted kidney.
"Thymoglobulin has been a well-established medication used in kidney transplantation for nearly 20 years, and this FDA approval is an important milestone for the transplant community," said Daniel Brennan, MD, Professor of Medicine, Director of Transplant Nephrology, Barnes-Jewish Hospital of Washington University School of Medicine in St. Louis. "Transplant rejection can be particularly discouraging for patients. The use of Thymoglobulin beginning just prior to transplantation may be an important step to ensuring a successful kidney implantation."
"Sanofi has been connected and committed to the kidney transplant community for decades. This FDA approval of Thymoglobulin for prophylactic use underscores our continued commitment to patients and their caregivers who will be receiving a potentially life-saving kidney transplant," said David Meeker, MD, Executive Vice President and Head, Sanofi Genzyme. "We remain focused on developing treatments for patients in need of new medications for life-threatening and limiting illnesses, including patients receiving a kidney transplant."
The FDA approval was based on two randomized multicenter studies comparing Thymoglobulin to interleukin-2 receptor antagonists (IL2RA: basiliximab or daclizumab) in deceased donor kidney transplant recipients. The first study in kidney transplant patients (n=278) at increased risk of acute rejection or delayed graft function showed a significantly lower incidence of the treatment failure as measured by a composite endpoint (biopsy-proven acute rejection, graft loss, death or lost to follow-up) within 12 months following transplantation in the Thymoglobulin group compared to patients in the basiliximab group (25 percent versus 38 percent; p=0.02).
The second study was an investigator-sponsored study in kidney transplant patients (n=230) at high immunological risk of rejection. Patients received either Thymoglobulin or daclizumab and also showed a lower incidence of treatment failure as measured by the composite endpoint 12 months following transplantation (25 percent versus 34 percent). The estimated between-treatment group difference (Thymoglobulin to daclizumab) was -9% (95% CI, -19.9% to 3.6%) demonstrating non-inferiority of Thymoglobulin compared with daclizumab.
The pooled analysis of both studies (n=508) showed a composite endpoint rate within 12 months post transplantation of 25.1 percent in the Thymoglobulin group compared with 36.0 percent in the IL2RA group. The estimated between-treatment group difference (Thymoglobulin to IL2RA) was -10.9% (95% CI, -18.8% to - 2.9%), which demonstrates superiority of Thymoglobulin for the prevention of acute rejection.
The most frequent adverse reactions seen in these clinical trials (more than 25% of patients receiving Thymoglobulin) include: leukopenia, hyperkalemia, urinary tract infection and pyrexia.
Thymoglobulin was originally approved by US regulatory authorities in 1998 for the treatment of renal transplant acute rejection. Thymoglobulin is marketed by Sanofi Genzyme, the specialty care global business unit of Sanofi.