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Adenovirus Drug Brincidofovir Shows Promise in Late-Stage Trial

Oral nucleotide analog demonstrates antiviral activity

Promising preliminary findings have been reported for the investigational antiviral agent brincidofovir (Chimerix, Inc.) showing improved survival in patients with adenovirus infection in the open-label pilot portion of the phase III AdVise trial. These data will be presented October 11 at the annual meeting of the Infectious Diseases Society of America (IDSA), to be held in Philadelphia, Pennsylvania.

The preliminary survival data, based on 48 evaluable patients from the ongoing AdVise study, showed a mortality rate of 35% compared with historic mortality rates of up to 80% in the first month after diagnosis. Most of the treated subjects also showed suppression or clearance of adenovirus from the blood.

Currently, there is no approved treatment for adenovirus, an infection that can progress rapidly in patients with a weakened immune system due to disease or medications. The virus causes upper respiratory infections, including the common cold, in individuals with a functional immune system, but it can lead to graft failure, severe pneumonia, hepatitis, or death in those with a weakened immune system, such as patients who have received a transplant.

The AdVise trial was initiated in March 2014 based on antiviral potency observed in vitro and on clinical data from a phase II trial and a large expanded-access study, which demonstrated the potential for improved clinical outcomes. As of September 19, 48 subjects had enrolled in AdVise, with a 35% (17/48) mortality rate observed during a median observation period of 57 days.

In the study, pediatric and adult patients with adenovirus infection are receiving brincidofovir twice weekly for 12 weeks. Baseline information and at least 2 months of follow-up data are available for 26 subjects. Of those patients, 23 had measurable viral loads at study entry, and three patients had no virus detectable in the blood but had been diagnosed with adenovirus infection. Fourteen of the 23 patients with viremia at study entry achieved undetectable viral loads during treatment. Twelve of the 26 patients died.

More than half of the subjects were hematopoeitic cell transplant (HCT) recipients with disseminated disease, but solid-organ transplant recipients and patients undergoing chemotherapy were also enrolled. More than one-third (10/26) of the subjects had a second active infection with another DNA virus in addition to adenovirus, including BK virus (27%), cytomegalovirus (19%) and Epstein-Barr virus (8%).

Brincidofovir is an oral nucleotide analog that has shown in vitro antiviral activity against all five families of DNA viruses that affect humans, including viruses in the herpes virus family and adenovirus. The drug has not been associated with kidney or bone-marrow toxicity in approximately 900 patients treated to date — side effects that can be treatment-limiting with currently available antivirals.

Brincidofovir has received a “fast track” designation from the FDA for cytomegalovirus (CMV), adenovirus, and smallpox.

Source: Chimerix, Inc.; October 8, 2014.

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