Brincidofovir is an experimental oral antiviral that is derived from cidofovir. It is showing antiviral activity against five viruses that affect humans. This drug is being developed by Chimerix of Durham, NC, and is being tested on adenovirus, cytomegalovirus, ebola virus, smallpox, and the herpes virus. The compound releases cidofovir intracellularly which produces lower plasma concentrations of cidofovir with the advantage of higher intracellular concentration of the agent.
Animal trials have shown the drug to have activity against adenovirus, smallpox, herpes simplex, cytomegalovirus and BK virus. In vitro tests show it to be paradoxically a possible treatment for Ebola, which is not a DNA virus (unlike adenovirus). Brincidofovir has been given to Ebola patients in the United States, the first being a patient who was already in critical condition when the treatment was initiated and who died after four days. The second patient survived and was released from the hospital virus-free.
Brincidofovir Adenovirus Treatment
In immune-compromised patients who develop adenovirus the mortality rate is up to 80 percent in the first month. To date there has been no real treatment beyond supportive measures. In the ongoing AdVise Trial the mortality rate is 35 percent, with a majority of patients showing adenovirus clearance or suppression. This is a huge advancement in the treatment of adenovirus in those whose immune system is weakened by disease, medication, or transplant.
Adult and pediatric patients are now being enrolled to receive brincidofovir adenovirus treatment twice a week for twelve weeks. Information is available for 26 subjects who have been followed for two months or longer. Viral load was detected in 23 of the 26, while three had no detectable viral load but were diagnosed with adenovirus infection. Fourteen of the 23 with detected viral load at the start of the study had no detectable virus during treatment. Twelve subjects died.
Solid organ transplant recipients as well as hematopoeitic cell transplant subjects were received into the study. Patients undergoing chemotherapy were also enrolled. Over a third of the patients had a second viral infection complicating the advenovirus, with a breakdown of 27 percent BK virus, 19 percent cytomegalovirus, and 8 percent Epstein-Barr virus.
Safety and tolerability was on par with other studies of brincidofovir in immune suppressed and compromised patients. Only three discontinued use due to adverse side effects. Six patients enrolled with adenovirus-related diarrhea and three of these remained stable while the other three showed symptomatic improvement.
AdVise is the Phase III trial evaluating brincidofovir for safety and efficacy in treating adenovirus. Chimerix is working with the FDA to design a Phase III study to follow the pilot study. Adenovirus infection in patients undergoing HCT transplants carries a mortality rate up to 80 percent, with no efficacious or approved treatment. In those with weakened immunity from transplant or disease, adenoviral infection can lead to severe pneumonia, hepatitis, graft failure and death. These trials are giving hope that there will be a real brincidofovir adenovirus treatment to add to the arsenal.