Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Transplant drug 2-year study outcomes show superior kidney function

03.05.2010
Two-year results from phase III clinical trials show the experimental immunosuppressive drug belatacept can better preserve kidney function in kidney transplant recipients while preventing graft rejection when compared with the standard immunosuppressive drug cyclosporine.

The two-year results from the three-year BENEFIT (Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial) and BENEFIT-EXT ("extended criteria") studies were presented Sunday at the American Transplant Congress in San Diego. A safety study that pooled long- term data also was presented.

In the BENEFIT trial, 666 patients were randomized to three groups and transplanted at 100 sites around the world, with 493 completing two years on treatment. In the BENEFIT-EXT study, 543 patients were randomized and transplanted, with 347 completing two years on treatment. The three treatment groups were less intensive (LI) and more intensive (MI) belatacept and a standard regimen of cyclosporine (CsA). All patients also received standard transplant regimens of the anti-T cell antibody basiliximab and drugs mycophenolate mofetil and corticosteroids.

Patient and graft survival after two years was similar among the belatacept and cyclosporine groups (94 percent MI; 95 percent LI; 91 percent CsA). The superior renal benefit of belatacept found after the first year of treatment was sustained in the second year, as measured by glomerular filtration rate. The improvement in cardiovascular/metabolic risk profile with belatacept remained in year two, with an additional beneficial effect noted in LDL cholesterol. Eight additional patients experienced an episode of acute rejection in year two (four with belatacept, four with cyclosporine), but in most cases this was successfully treated with drugs and did not lead to graft failure.

The overall incidence rate of malignancies and serious infections remained comparable across the groups. Although in the second year there remained a higher incidence of post-transplant lymphoproliferative disorder (PTLD)–five belatacept patients vs. one cyclosporine patient–the overall safety profile remained similar across the groups. No additional benefits were seen in the MI vs. the LI belatacept group.

"Our goal in transplantation is to achieve a normal life span for our patients, and to have them survive dialysis-free with a functioning transplanted organ for that life span," says Christian P. Larsen, MD, DPhil, director of the Emory Transplant Center and chair of the Department of Surgery in Emory University School of Medicine.

"Today, the median survival of a transplant remains about 8-10 years, far short of what we'd like," Larsen adds. "While the calcineurin inhibitors, cyclosporine and tacrolimus, are potent immunosuppressant drugs, they are associated with multiple toxicities that limit transplant success. We have been working for years to develop new therapies that avoid the main complications and causes of death, including cardiovascular events, infections and malignancies. Our data with belatacept indicate it can better preserve kidney function while improving the risk for these complications."

Larsen, along with fellow Emory University transplant surgeon and researcher Thomas C. Pearson, MD, DPhil, Emory professor of surgery and co-director of the kidney/pancreas transplant program at the Emory Transplant Center, made significant research contributions to the development of belatacept, in collaboration with other investigators at Emory, the Yerkes National Primate Research Center, and Bristol Myers Squibb.

A third study, which pooled safety data from phase II and phase III studies over 2.4 to 7 years, found that longer-term treatment with belatacept-based regimens was generally safe. The incidence of deaths and serious adverse events were lowest in the belatacept LI group. The overall incidence of malignancies remained low, but was slightly higher in the MI group. The incidence of herpes infections and tuberculosis (mostly in endemic areas) was low overall, but higher in the belatacept groups. Fifteen cases of PTLD occurred (13 with belatacept, 2 with cyclosporine), mainly in patients not previously exposed to Epstein-Barr virus, which many humans have as a low-level chronic infection. The researchers say PTLD might be reduced by avoiding use of belatacept in Epstein-Barr-naïve patients.

Belatacept is a "costimulation blocker" that inhibits one of two signals T cells require to trigger an immune response. It is a modified version of a fusion protein known as CTLA4-Ig, which mimics a regulatory molecule found on T cells and acts as a decoy. CTLA4-Ig (commercial name: abatecept/Orencis) is FDA approved to treat rheumatoid arthritis.

The clinical trials were sponsored by Bristol Myers Squibb. Dr. Larsen is an unpaid consultant to Bristol Myers Squibb on belatacept.

American Transplant Congress Abstracts (Embargoed until 7 p.m. ET, Sunday, May 4, 2010): Belatacept vs Cyclosporine in Kidney Transplant Recipients: Two-Year Outcomes from the BENEFIT Study: C.P. Larsen et.al.

Belatacept vs. Cyclosporine in ECD Kidney Transplants: Two-Year Outcomes from the BENEFIT-EXT Study: A. Durrbach, et.al.

Safety Profile of Belatacept in Kidney Transplant Recipients from a Pooled Analysis of Phase II and Phase III Studies: J. Grinyo, et.al.

The Robert W. Woodruff Health Sciences Center of Emory University is an academic health science and service center focused on missions of teaching, research, health care and public service. Its components include the Emory University School of Medicine, Nell Hodgson Woodruff School of Nursing, and Rollins School of Public Health; Yerkes National Primate Research Center; Winship Cancer Institute of Emory University; and Emory Healthcare, the largest, most comprehensive health system in Georgia. Emory Healthcare includes: The Emory Clinic, Emory-Children's Center, Emory University Hospital, Emory University Hospital Midtown, Wesley Woods Center, and Emory University Orthopaedics & Spine Hospital. The Woodruff Health Sciences Center has $2.3 billion in operating expenses, 18,000 employees, 2,500 full-time and 1,500 affiliated faculty, 4,500 students and trainees, and a $5.7 billion economic impact on metro Atlanta.

Learn more about Emory's health sciences: http://emoryhealthblog.com - @emoryhealthsci (Twitter) - http://emoryhealthsciences.org

Kathi Baker | EurekAlert!
Further information:
http://www.emory.edu

More articles from Studies and Analyses:

nachricht New study: How does Europe become a leading player for software and IT services?
03.04.2017 | Fraunhofer-Institut für System- und Innovationsforschung (ISI)

nachricht Reusable carbon nanotubes could be the water filter of the future, says RIT study
30.03.2017 | Rochester Institute of Technology

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

Bare bones: Making bones transparent

27.04.2017 | Life Sciences

Study offers new theoretical approach to describing non-equilibrium phase transitions

27.04.2017 | Physics and Astronomy

From volcano's slope, NASA instrument looks sky high and to the future

27.04.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>