FDA’s advisory panel voted 13 to 5 to recommend Bristol-Myers Squibb’s Belatacept for approval as a prophylaxis of acute rejection in de novo kidney transplant patients. The PDUFA date has been set for May 1.
On February 25, FDA voiced some concerns over post-transplantation complications and the occurrence of progressive multifocal leukoencephalopathy (PML) associated with Belatacept treatment in clinical development. Bristol-Myers Squibb pointed out that its data showed Belatacept avoids toxicities seen with cyclosporine (CsA), another rejection drug, with fewer deaths and serious infections. The firm also noted that its therapy reduced the risk of diabetes and improved blood pressure.
The Cardiovascular and Renal Drugs Advisory Committee based its recommendation on data from Phase II and two Phase III trials that included more than 1,000 patients who received Belatacept. One of the Phase III studies was in standard criteria (living or deceased) donor kidney transplants and one in extended criteria donor kidney transplants.
The committee’s vote was to approve the less-intensive (LI) regimen of Belatacept in Epstein-Barr virus positive kidney transplant patients, report Seamus Fernandez and Kathryn C. Alexander, pharmaceuticals analysts at Leerink Swann. Most panel members agreed the safety profile was sufficient to support approval despite being nervous about PML, they add.
However, half the panel stated that they'd like to see more long-term data to make a decision on the efficacy profile. Fernandez and Alexander note that the panel pointed out that noninferiority studies are difficult to interpret and “rest on a very unstable foundation.” These panel members agreed that three-year data would be required to properly analyze the drug's efficacy.
Transplant surgeons on the panel were generally more bullish than the cardiologists and biostatisticians, citing the need for alternatives to CsA in treating kidney transplant patients, according to Fernandez and Alexander.
Belatacept is a fusion protein designed to be a selective co-stimulation blocker that binds to a specific site on certain antigen-presenting cells of the immune system to block the second signal necessary to activate naïve T cells, which coordinate immune-mediated rejection of transplanted organs.
Fernandez and Alexander forecast Belatacept U.S. revenues of $50 million in this year and $650 million by 2016.