CMX001 Prevents CMV Disease in Transplant Recipients

Larry M. Baddour, MD

This novel agent — 100 mg twice weekly — was effective in preventing cytomegalovirus disease in hematopoietic-cell transplant recipients, with no evidence of myelosuppression or nephrotoxicity.

A safe, effective regimen is needed for the prevention and control of cytomegalovirus (CMV) infection in allogeneic hematopoietic-cell transplant recipients. A novel, orally bioavailable agent, CMX001, is of keen interest because it is converted intracellularly to cidofovir but is not concentrated in the renal tubules like cidofovir and is thus less likely to have nephrotoxicity. Moreover, CMX001 is approximately 400 times more potent than cidofovir against CMV (including ganciclovir-resistant strains) in vitro and is effective against CMV disease in animal models. In a recent manufacturer-funded, randomized, placebo-controlled trial, researchers evaluated its safety and anti-CMV activity in humans.

CMV-seropositive allogeneic hematopoietic-cell recipients aged ≥18 were recruited from 27 centers in the U.S.; ultimately, 230 patients were included in the intention-to-treat analysis. The study drug — CMX001 at one of five doses or placebo — was initiated between 14 and 30 days posttransplantation and continued until posttransplantation week 13.

Incidence of the primary endpoint (failure to prevent progressive CMV infection — i.e., either development of CMV disease or a plasma CMV DNA level >200 copies/mL ≤1 week after the last study-drug dose) was significantly lower in the group that received CMX001 at a dose of 100 mg twice weekly than in the placebo group (10% vs. 37%; P=0.002). No evidence of myelosuppression or nephrotoxicity was seen. Diarrhea, however, was a dose-limiting adverse event at 200 mg twice weekly.

CITATION(S):

Marty FM et al. CMX001 to prevent cytomegalovirus disease in hematopoietic-cell transplantation. N Engl J Med 2013 Sep 26; 369:1227.