Effect of CMX001 on Levels of DNA Virus In Patients After Allogeneic Stem Cell Transplantation.

Abstract 4550

Latent viral infections occurring in the post bone marrow transplant period remain a significant clinical problem. New and effective antiviral drugs (AVD) are needed to provide adequate therapy for infected patients. We report the use of a new oral AVD, CMX001 (Chimerix Inc. Durham, NC) to treat DNA virus infections in six severely ill patients.

All patients had grade 2 or greater gut graft versus host disease (GVHD) during or after CMX001 treatment. The Table shows viral levels before and after treatment with CMX001 twice/wk. Pt 1's AV cycle number fluctuated and never cleared. A higher cycle number indicates less virus. Pt 2 cleared AV from blood after first dose, but urine, stool, gut biopsies remained AV positive. Pt 3's HHV6 plasma PCR levels fluctuated, but the pericardial fluid levels had cleared at autopsy. Pt 4 did not have pre dosing blood BKV PCR levels taken and his subsequent blood BKV low level was measurable (below the positive limit level). Interestingly, however, the patient's BKV related hemorrhagic cystitis (HC) symptoms resolved after 4 doses of CMX001. Pt 5's BKV HC symptoms also resolved after 4 doses of drug, and his positive blood viral level cleared after 6 doses. Pt 6 discontinued drug because of abdominal pain and the need for NPO, but his hemorrhagic cystitis symptoms had abated. No specific toxicities were documented in these severely ill patients with gut GVHD, but gut pain and transient thrombocytopenia were observed. In summary, one of 2 pts with AV cleared their blood. BKV was not cleared from urine, but 2/4 cleared BKV from blood. One patient with HHV6 did not clear blood DNA viral levels, but did clear pericardial fluid. In both cases of HC, symptoms resolved. Thus, CMX001 shows promise as new antiviral drug given its ability to decrease DNA viral levels in this small group of critically ill patients.