Chimerix said today that its antiviral candidate, brincidofovir, for patients undergoing hematopoietic cell transplantation (HCT) failed its first Phase III trial, with deaths and cytomegalovirus (CMV) infection exceeding the control arm.
Brincidofovir missed its primary endpoint in the Phase III SUPRESS trial by failing to prevent clinically significant cytomegalovirus (CMV) infection through week 24 after transplant.
While fewer patients in the brincidofovir arm had a CMV infection from the on-treatment period through week 14 after HCT, consistent with positive antiviral results seen in the Phase II study, CMV infections in the brincidofovir arm increased compared to the control arm from week 14 to week 24, Chimerix reports.
Patients in the brincidofovir arm also showed an increase in mortality compared to the control arm, but the increase was not statistically significant, according to Chimerix.
The company's report states that a preliminary analysis suggested the primary endpoint failures in CMV infections and mortality in the brincidofovir arm were driven by confirmed cases of graft-versus-host-disease (GVHD), which resulted in a significantly higher use of corticosteroids than in the control arm. Both GVHD and use of corticosteroids are risk factors for “late” CMV infection that occurs after discontinuation of the antiviral in HCT recipients, it adds.
“While we are clearly disappointed in the top-line results from SUPPRESS, we remain committed to better understanding the full data set as we consider potential paths forward for brincidofovir,” Chimerix president and CEO M. Michelle Berrey, M.D., MPH, said in a statement. “With a strong cash position, an experienced leadership team, and brincidofovir patent exclusivity through 2034, we continue to believe there is a viable path forward for the development of brincidofovir.”
Chimerix said a full analysis of the SUPPRESS trial results is ongoing and will be presented at the BMT Tandem Meetings in Honolulu, Hawaii, to be held February 18–22, 2016.
“We will be evaluating the sub-groups of patients within SUPPRESS, such as T-cell depleted transplant recipients who have a lower risk of GVHD, to better understand these results and inform our next steps,” adds Chimerix CMO W. Garrett Nichols, M.D. He also says Chimerix is in contact with the FDA and other regulators, and will reach out to experts to assess why SUPPRESS trial results differed from those of the Phase II study.
Chimerix says it will “pause” further enrollment in two other Phase III trials—the SUSTAIN and SURPASS trials in kidney transplant recipients—but plans to continue clinical programs testing brincidofovir in serious adenovirus infections and in smallpox.
“With data currently in hand, we believe that brincidofovir may ultimately demonstrate a positive risk-benefit profile for the treatment of adenovirus and smallpox, as well as use in other populations in need of a novel compound for DNA viral infections,” Dr. Nichols added.