Brincidofovir: Additional Phase III data

Additional data from the double-blind, international Phase III SUPPRESS trial in 452 CMV-seropositive hematopoietic stem cell transplant (HSCT) recipients showed that 51% of patients who received twice-weekly 100 mg oral brincidofovir had clinically significant CMV infection at week 24, the primary endpoint, vs. 52% of patients who received placebo. At week 14, 24% of patients who received brincidofovir had clinically significant CMV infection vs. 38% of patients who received placebo (p=0.002). Patients received brincidofovir or placebo during the 14 week on-treatment period following HSCT and then were followed from weeks 14 to 24 in an off-treatment period. Chimerix said the trial’s miss “appears to be associated with CMV events” in the off-treatment period in patients receiving brincidofovir that were driven by higher use of corticosteroids and other immune suppressing therapies used to treat presumptive graft-versus-host disease (GvHD).

Diarrhea -- a symptom of GvHD in the gut -- was more frequent in the brincidofovir arm and was often presumed to be gut GvHD and was treated with corticosteroids, rather than temporarily interrupting study drug. Additionally, there was an 8-fold increase in the use of corticosteroids through week 14 in the brincidofovir arm vs. the placebo arm (mean cumulative prednisone equivalent of 26 mg/kg vs. 3 mg/kg). The rate of CMV infections was 22% in the brincidofovir arm between weeks 14 and 24 vs. 11% in the placebo arm. Brincidofovir also missed the secondary endpoints of preventing infection with non- CMV DNA viruses, such as BK virus (BKV), and of reducing all-cause mortality (15.5% vs. 10.1%, p=0.12) vs. placebo. The most common adverse events reported were acute GvHD, gastrointestinal events and liver enzyme abnormalities. Data were presented at the BMT Tandem Meetings in Honolulu. ...