Belatacept looks promising for kidney transplant patients
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“While the conventional immunosuppressants are potent, they are associated with multiple toxicities that limit transplant success. |
Two-year results from Phase III trials show the experimental immunosuppressive drug belatacept can better preserve kidney function in transplant recipients while preventing graft rejection than the standard immunosuppressive drug cyclosporine, a calcineurin inhibitor.
Though belatacept and cyclosporine have similar graft survival rates at the one- and two-year marks, patients receiving belatacept had higher kidney function and lower blood pressure and cholesterol, according to results from a clinical trial that tracked more than 600 patients. Belatacept also can be given every few weeks compared with calcineurin inhibitors, which are taken twice every day.
Most transplant patients take calcineurin inhibitors to suppress their immune systems and to prevent rejection of the kidney, but the drugs can damage kidneys and lead to high blood pressure and diabetes.
Belatacept inhibits one of two signals T cells require to trigger an immune response. The drug is a modified version of CTLA4-lg, also known as abatecept, which is used to treat rheumatoid arthritis.
Emory transplant surgeons Christian Larsen and Thomas Pearson worked with researchers at Bristol Myers Squibb in developing the drug. Larsen and Pearson found in the 1990s that CTLA4-lg could control graft rejection in mice but worked less well in non-human primates. Researchers at Bristol then found two drug mutations that made CTLA4-lg bind more tightly to its target, and Larsen and Pearson picked up the research from there.
“Today, the median survival of a transplant remains about eight to 10 years, far short of what we’d like,” Larsen says. “While the conventional immunosuppressants are potent, 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.”
Bristol Myers Squibb had expected belatacept to be approved by the FDA in May, but the agency has requested three-year data from the Phase III studies to further evaluate long-term effects of the drug. The application submitted included two-year data.
