Dealing with adenovirus

DURHAM, N.C.—Chimerix, Inc., a biopharmaceutical company developing novel, oral antivirals in areas of high unmet medical need, has announced preliminary data from liver transplant patients who received brincidofovir for adenovirus infection through the ongoing AdVise trial and the brincidofovir expanded access program. These data were to be presented at IDWeek in San Diego.

Twelve pediatric patients and one adult patient who were infected with adenovirus following receipt of a liver transplant, either alone or as part of a multi-organ transplantation, were identified from the AdVise trial and the brincidofovir expanded access program. Eight out of the thirteen patients had disseminated adenovirus disease, with high levels of adenovirus in the blood and/or adenovirus recovered from multiple organ systems. Patients were treated with brincidofovir for a median of 79 days (range: 4 to 180 days). Patients were assessed for changes in adenovirus viral load from baseline, time to nadir viral load, survival, and adverse events.

All patients with adenovirus viremia or localized infection (n=5) survived; seven of eight patients with disseminated adenovirus disease survived. Two patients experienced serious brincidofovir-related adverse events (diarrhea and increased stool volume, respectively), and no brincidofovir-associated liver adverse events were reported. In ten of eleven patients for whom viral load data were available, adenovirus levels in blood were either below quantifiable levels or were undetectable by the end of treatment, with median time to minimum viral load of 15 days (range: 4 to 96 days).

In liver transplant recipients, adenovirus typically causes jaundice, hepatomegaly, and hepatitis, with mortality rates as high as 50 percent in pediatric liver transplant patients.

"Adenovirus has been reported in up to 10 percent of pediatric liver transplant patients, but may be underdiagnosed," said W. Garrett Nichols, M.D., M.S., chief medical officer of Chimerix. "With no current FDA-approved treatment for adenovirus infection, there is a great unmet medical need for immunocompromised patients, including liver transplant recipients. These data support the continued study of brincidofovir for the prevention and treatment of double-stranded DNA virus infections, including adenovirus, in solid organ transplant recipients."

Adenovirus causes upper respiratory infections, including the common cold, in individuals with a functional immune system. However, in people with a weakened immune system, such as patients who have undergone a transplant, adenovirus can lead to life-threatening infections, including pneumonia and hepatitis. Disseminated adenovirus disease can be associated with a mortality rate of up to 80 percent in patients who are undergoing hematopoietic cell transplant (HCT), or bone marrow transplant. No therapies are approved for the treatment of adenovirus.

Brincidofovir (CMX001), Chimerix's lead product candidate, is an oral nucleotide analog that has shown in-vitro antiviral activity against all five families of DNA viruses that affect humans, including the herpes viruses and adenovirus. Brincidofovir has not been associated with kidney or bone marrow toxicity in over 1,000 patients treated to date. Based on the clinically and statistically significant Phase 2 results in cytomegalovirus (CMV) prevention, Chimerix initiated the 450 patient Phase 3 SUPPRESS trial, which completed enrollment in June 2015. If positive, data from SUPPRESS will support Chimerix's initial regulatory submission for brincidofovir for the prevention of CMV infection in adult HCT recipients. Chimerix has also completed enrollment in AdVise, the open-label trial of brincidofovir for the treatment of disseminated or localized adenovirus infection in patients at increased risk of rapid progression to disseminated disease. AdVise completed enrollment in August 2015. Chimerix is working with the Biomedical Advanced Research and Development Authority (BARDA) to develop brincidofovir as a medical countermeasure against smallpox. Brincidofovir has received Fast Track designation from the FDA for CMV, adenovirus, and smallpox.

Chimerix is a biopharmaceutical company dedicated to discovering, developing and commercializing novel, oral antivirals in areas of high unmet medical need. Chimerix's proprietary lipid conjugate technology has produced brincidofovir (CMX001), a clinical-stage nucleotide analog, CMX157 which was licensed to ContraVir Pharmaceuticals in 2014, and early clinical candidates including CMX669.