GAITHERSBURG, MdODAC has declined to recommend that the
FDA approve Prograf (tacrolimus, Fujisawa Healthcare) for the
prophylaxis of graft-versus-host disease (GVHD) in patients receiving
allogeneic bone marrow transplants (BMT).
Fujisawa presented data from two phase III randomized studies
involving 509 patients who received either sibling-matched BMTs or
transplants from unrelated donors: 255 received Prograf and 254
cyclosporine (Sandimmune). All patients received methotrexate.
The primary endpoint was reduction in acute moderate-to-severe GVHD
at 100 days after transplant. The incidence of grade 2-4 GVHD (26% vs
41% and 51% vs 70%) favored Prograf in both studies. In the
matched-sibling study, there were more advanced disease patients in
the Prograf group, which accounted for a greater incidence of deaths
at 6 months (42% vs 32%), the company said. In the unrelated donor
study, there was no difference in the incidence of deaths between
Prograf and cyclosporine (34% and 38%, respectively).
FDA reviewer Steven Hirschfeld, MD, noted that more Prograf patients
went on to dialysis and more suffered a relapse than did patients on
cyclosporine. If we understood the relationship between the
drugs and the deaths, I think we would feel more comfortable about
making a recommendation, said Richard M. Simon, DSc, of the NCI.