Drug may still be viable as CMV prophylaxis
The investigators said the numerical differences in mortality appear to be driven by higher use of corticosteroids and other immunosuppressive therapies in the subjects who received brincidofovir.
The rate of treatment-emergent adverse events (AEs) was 100% in the brincidofovir arm and 98% in the placebo arm. The rate of grade 3 or higher AEs was 67% and 38%, respectively. The rate of serious AEs was 57% and 38%, respectively.
The rate of AEs leading to treatment discontinuation was 26% and 7%, respectively. And the rate of AEs leading to treatment change or interruption was 45% and 15%, respectively.
The most common AEs in the brincidofovir arm were diarrhea (61%), acute GVHD (57%), abdominal pain (34%), nausea (31%), vomiting (24%), peripheral edema (17%), hyperglycemia (16%), hypokalemia (16%), hypomagnesemia (13%), and ALT elevation (11%). There was no evidence of bone marrow toxicity, kidney toxicity, or viral resistance to brincidofovir.
Brincidofovir development
Chimerix said it will discuss the SUPPRESS data in full with the US Food and Drug Administration and other regulators, including the benefit-to-risk profile in specific subpopulations, as well as the current adenovirus and smallpox data, to determine next steps for the brincidofovir clinical programs.
The development of an intravenous (IV) formulation of brincidofovir is progressing toward clinical testing and has the potential to avoid the gastrointestinal side effects of orally administered brincidofovir.
Preclinical studies of IV brincidofovir have shown a lower risk of gastrointestinal effects based on maintained body weight during dosing and no evidence of injury in preliminary review of the gastrointestinal tract.
If human studies continue to support these findings, IV dosing during the first few weeks after transplant when patients are recovering from conditioning chemotherapy could be explored, with oral brincidofovir therapy available as patients are discharged home.
As there is no preventive therapy approved for CMV in HSCT recipients, Chimerix said it is committed to moving brincidofovir forward in this indication. Plans for brincidofovir in HSCT recipients will be the subject of further discussions with regulators. 
