The need for an alternative to calcineurin inhibitors was enough to sway an FDA panel that belatacept from Bristol-Myers Squibb Co. deserves to be approved to prevent organ rejection in renal transplant patients, despite concerns about the compound's efficacy and safety.
Last week, FDA's Cardiovascular and Renal Drugs Advisory Committee voted 13-5 that belatacept had a positive benefit-risk profile for the prevention of organ rejection in renal transplant recipients.
Panel members did have concerns about FDA's reanalysis of data from the Phase III trials, which showed belatacept was numerically worse than cyclosporine in preventing acute rejections. However, because belatacept fell within the 20% noninferiority margin established by the agency, they agreed it demonstrated efficacy.
The committee also was concerned about the rates of post-transplant lymphoproliferative disorder (PTLD) and progressive multifocal leukoencephalopathy (PML) in the belatacept arms of Phase II and Phase III trials.
On the other hand, the panel was impressed with belatacept's improvement of glomerular filtration rate (GFR) compared to cyclosporine - an endpoint FDA agreed to in an SPA but then reneged after the trial was underway.
Given the tradeoffs, the panel endorsed belatacept for use in a restricted population, and only if a strict patient registry was put in place to monitor the rates of PTLD and PML.
Benefits vs. tox
About 17,000 kidney transplants are performed in the U.S. each year. To prevent graft loss, patients must take a series of immunosuppressants.