Chimerix, Inc., a biopharmaceutical company developing novel, oral antivirals in areas of high unmet medical need, has started dosing in the phase III SUPPRESS trial (ClinicalTrials.gov ID: NCT01769170). SUPPRESS is evaluating brincidofovir (CMX001) for the prevention of cytomegalovirus (CMV) infection, the most significant infectious disease in hematopoietic cell transplant (HCT) recipients.

Brincidofovir is an investigational oral nucleotide analog lipid-conjugate that has demonstrated activity against all pathogenic double-stranded DNA (dsDNA) viruses, including herpesviruses, adenoviruses, and polyomaviruses.

"Initiation of our phase III SUPPRESS trial marks a significant milestone in the development program for brincidofovir," said Kenneth I Moch, president and CEO of Chimerix. "A well-tolerated and effective prevention for CMV disease in hematopoietic cell transplant patients remains an important unmet medical need, as existing antiviral therapies are limited by significant hematologic and renal toxicities."

SUPPRESS is designed to demonstrate the efficacy and safety of brincidofovir for the prevention of CMV infection versus a placebo control, as no therapy is currently approved for the prevention of CMV in HCT recipients. The primary endpoint for SUPPRESS is prevention of clinically significant CMV infection through the first 24 weeks post-transplant. The trial is powered to detect a relative 50 per cent decrease in clinically significant CMV infection in subjects receiving brincidofovir versus those receiving placebo. Secondary endpoints in the SUPPRESS trial include evidence of other dsDNA viruses, including adenovirus (AdV), varicellovirus (VZV), BK virus (BKV), and other herpesviruses such as HHV-6, which contribute to morbidity and mortality in the first year following HCT.

SUPPRESS is anticipated to enroll approximately 450 HCT recipients who are at increased risk of CMV infection, with approximately 300 of the 450 enrolled subjects receiving twice weekly (BIW) brincidofovir versus placebo (2-to-1 ratio). Dosing of study drug will begin shortly after subjects receive their transplant, and will not require evidence of stem cell "engraftment" (evidence of production of blood cells by the new transplant), a safety precaution in the phase II trial of brincidofovir and other recent trials of investigational antivirals for CMV prevention. The ability to begin prevention during the early post-transplant period may decrease the risk of CMV infection in transplant patients.  

Subjects enrolled in SUPPRESS will receive brincidofovir or placebo from the early post-transplant period through Week 14 post-transplant, the period of highest risk for viral reactivation. Enrolled subjects will continue to be monitored for evidence of CMV reactivation and other dsDNA viral infections through Week 24 post-transplant. The recently approved Roche TAQMAN real-time polymerase chain reaction assay will be used to monitor levels of CMV in the blood. Approximately 40 transplant centres will participate in SUPPRESS.

Data from SUPPRESS are anticipated in 2015 and, if positive, may support Accelerated Approval of brincidofovir for the prevention of CMV infection.

"Initiation of patient dosing in SUPPRESS advances the development program for brincidofovir, which has the potential to make a meaningful difference in the lives of immunocompromised patients," said M Michelle Berrey, MD, MPH, chief medical officer of Chimerix. "Because transplant patients are too often faced with the clinical consequences of multiple dsDNA viral infections, brincidofovir with its broad spectrum antiviral activity has the potential to improve overall outcomes in patients undergoing HCT, through both direct and indirect effects of prevention of CMV and other dsDNA viral infections."

In addition to the ongoing phase III SUPPRESS trial, Chimerix has recently announced top line data from a phase II trial of brincidofovir for AdV infection in pediatric and high-risk adult HCT recipients. Results from this trial will be presented as a late-breaker at the annual ICAAC Conference on September 10, 2013.

CMV is a member of the herpesvirus family and the most common infectious pathogen in transplant recipients.

Chimerix is committed to the discovery, development and commercialization of novel, oral antiviral therapeutics designed to transform patient care in areas of high unmet medical need.