Chimerix :Phase 3 SUPPRESS Trial Of Brincidofovir Fails To Meet Primary Endpoint

(RTTNews) - Chimerix (CMRX) said that its Phase 3 SUPPRESS trial of brincidofovir in patients undergoing hematopoietic cell transplantation or HCT did not achieve its primary endpoint for the prevention of clinically significant cytomegalovirus or CMV infection through Week 24 after transplant.

During the on-treatment period through Week 14 after HCT, fewer patients in the brincidofovir arm had a CMV infection, consistent with the positive antiviral effect of the compound seen in the Phase 2 study. However, during the 10 weeks off treatment from Week 14 to Week 24, there was an increase in CMV infections in the brincidofovir arm compared to the control arm. There was also a non-statistically significant increase in mortality in the brincidofovir arm compared to the control arm.

Preliminary analysis suggests that the primary endpoint failures in both the prevention of CMV infections and mortality in the brincidofovir arm were driven by confirmed cases of graft-versus-host-disease or 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.

The rate of study drug discontinuation for gastrointestinal events was <10%, comparable to that observed in the Phase 2 trial of brincidofovir in a similar HCT population.

Chimerix noted that it plans to continue the programs testing brincidofovir in serious adenovirus infections and in smallpox. In the open-label AdVise trial for patients with disseminated adenovirus infection, a <40% mortality was reported in February 2015 at a mean of 10 weeks of observation. In an updated preliminary analysis of the full Cohort B population of HCT recipients with disseminated adenovirus infection, all-cause mortality at day 90 remains <40%, continuing to support a potential positive risk:benefit for the treatment of adenovirus infection.

In an animal model of smallpox infection, the 100 percent survival data announced earlier this year supports continued development of a short course of brincidofovir for the treatment of smallpox.

Pending the availability of complete data from SUPPRESS, including secondary endpoints in other dsDNA viral infections, Chimerix has elected to pause further enrollment in the Phase 3 SUSTAIN and SURPASS trials in kidney transplant recipients.