Belatacept, an investigational drug to counter organ rejection following transplants could lead to potential side-effects including death despite its obvious advantages in improving kidney function, according to the US Food and Drug Administration.
US FDA is currently reviewing belatacept developed by Bristol-Myers Squibb for marketing approval.
Clinical trial results of belatacept showed improvements in heart risks, kidney function and other factors. But post-transplantation complication and a rare disorder called progressive multifocal leukoencephalopathy (PML) are still a concern, the FDA reviewers said.
Belatacept is a fusion protein designed to be a selective co-stimulation blocker that binds to a specific site on certain cells of the immune system (i.e., antigen presenting cells) to block the second signal necessary to activate naïve T-cells, which coordinate immune-mediated rejection of transplanted organs.
Costimulation signals are required for full T-cell activation and they play a vital role in the development of immune responses.
The CD28:B7 pathway is the most thoroughly characterized costimulation pathway. Recombinant technology has enabled the development of fusion proteins that competitively inhibit the interactions of both B7 molecules (CD80 and CD86) with their receptors, and belatacept represents the first example of a rationally designed immunosuppressive fusion protein that results in enhanced blockade of a critical T-cell costimulatory pathway.
Allogeneic stimulation assays demonstrated the increased inhibition of both primary and secondary T-cell proliferative responses by belatacept compared with the parent compound abatacept.
In renal transplant studies performed in rhesus monkeys, a significantly longer median survival time of renal allografts (155 days) was obtained following treatment with belatacept in addition to a regimen of mycophenolate mofetil and methylprednisolone (30 days without belatacept).
In a multicenter, randomized, parallel-group phase II study in patients undergoing renal transplantation, the incidence of acute rejection at 6 months was similar between groups who received an intensive regimen of belatacept, a less intensive regimen of belatacept or cyclosporin for primary maintenance immunosuppression.
In addition, belatacept has demonstrated preliminary efficacy in the treatment of rheumatoid arthritis. It is currently in phase III development for the treatment of kidney transplant rejection.
Belatacept helps prevent graft rejection and maintain kidney function following renal transplantation.
In September last year, Bristol-Myers Squibb Company announced that US FDA has accepted the company’s submission of a biologic license application for belatacept, which was in ongoing phase III development for use in kidney transplantation.
Bristol-Myers Squibb is a biopharmaceutical company whose mission is to extend and enhance human life.