(ChemotherapyAdvisor) – A reduction in new or progressive cytomegalovirus (CMV) infection occurred in allogeneic hematopoietic stem cell transplant recipients who received the oral antiviral compound CMX001, according to results of the first Phase 2 trial of this agent presented at the American Society for Blood and Marrow Transplantation/Center for International Blood & Marrow Transplant Research 2012 BMT Tandem Meetings.
“This study provides positive data supporting the antiviral activity of CMX001 at different dose levels, and a better understanding of CMX001’s safety and tolerability as a prophylactic agent against CMV infection, a major cause of morbidity and mortality in bone marrow transplant recipients,” said Francisco Marty, MD, of Dana-Farber Cancer Institute and Brigham and Women’s Hospital on behalf of his colleagues. “There is a substantial unmet medical need for safer and effective therapies against CMV.”
The randomized, double-blind, dose-excalation, placebo-controlled, multicenter study enrolled 230 adult allogeneic CMV-seropositive stem cell transplant recipients. Following engraftment (days 14–30 posttransplant), patients were stratified based on presence or absence of acute GVHD requiring systemic therapy and presence or absence of CMV DNA in plasma and randomized 3:1, CMX001 vs. placebo, into five sequential, dose-escalating cohorts.
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Subjects were treated either once or twice weekly with CMX001, a broad spectrum lipid-antiviral-conjugate that delivers high intracellular levels of the active antiviral agent, cidofovir-diphosphate, for 9 to 11 weeks until week 13 posttransplant followed by a 4- to 8-week safety follow-up period.
At 13 weeks, CMX100 met the primary endpoint, a statistically significant reduction in CMV viremia (CMV >200copies/mL) or disease at the end of treatment vs placebo (P=0.001).
Three different doses of CMX001—200mg once weekly, 100mg twice weekly, and 200mg twice weekly—also demonstrated statistically significant reductions in proportion of subjects with CMV viremia ≥1000 copies/mL at any time during treatment vs placebo (P=0.002, <0.001, <0.001, respectively). In those who were CMV viremia negative prior to treatment, four different CMX001 dose regimens (both 100mg and 200mg once or twice weekly) demonstrated statistically significant reduction vs. placebo.
Changes in renal and graft function were similar across all cohorts during treatment and follow-up, the investigators noted. The most common adverse event reported was diarrhea, which was dose-limiting at the highest CMX001 dose, 200mg twice weekly.
CMX001 is being developed by Chimerix, Inc., Research Triangle Park, NC.
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