Brincidofovir (CMX001) for the Treatment of Serious or Life-Threatening Double-Stranded DNA Virus Infections in Patients Receiving Liver Transplant as Part of Multiorgan Transplantation.

Abstract

Background: Infectious complications remain an important cause of morbidity/mortality following SOT. Brincidofovir (BCV), a nucleotide analog active in vitro against all major human pathogenic dsDNA viruses, is in Phase 3 development for CMV prevention in HCT. Over 400 patients (pts) have received BCV for serious or life-threatening infections with dsDNA viruses under compassionate use (Study CMX001-350, clinicaltrials.gov ID: NCT01143181 or under emergency INDs). Methods: Ten multiorgan transplant pts (liver ± kidney/pancreas/small bowel) were treated for serious or life-threatening AdV, BKV, CMV, EBV or VZV infections after failing existing antiviral therapies. BCV was given orally at 2-4 mg/kg or 100-200 mg twice-weekly. Results: Pt demography and virologic responses [viral load (VL) at baseline (BL) and maximal (Max) and through end-of-treatment (EOT) decreases]/infection outcomes are summarized in the table:Table: No Caption available.ND=no data; NV=no viremia; R=infection resolved; VR=virologic response; *=undetectable (<100 c/mL) Two pts died on treatment (#7 intracranial haemorrhage, #10 hepatic failure secondary to aortic thrombus, both unrelated to BCV); 2 pts died >30 days posttreatment (#1 PTLD/Pseudomonas pneumonia, #3 septic shock). No adverse events (AEs) required BCV treatment discontinuation and there were no serious drug-related hepatic AEs. Conclusions: These data support the continued study of BCV in the treatment of dsDNA virus infections in SOT and other immunocompromised pts. There were no treatment-limiting AEs and some evidence of improved outcomes, although conclusions are limited by the small sample size and uncontrolled data collection. DISCLOSURES:Florescu, D.: Grant/Research Support, Chimerix, Inc., Other, Chimerix, Inc., Former/current investigator for CMX001 trial. Grimley, M.: Other, Chimerix, Inc., Former/current investigator for CMX001 trials. Nemecek, E.: Other, Chimerix, Inc., Former/current investigator for CMX001 trials. Chittick, G.: Employee, Chimerix, Inc., Stockholder, Chimerix, Inc. Brundage, T.: Employee, Chimerix, Inc., Stockholder, Chimerix, Inc. Mommeja-Marin, H.: Employee, Chimerix, Inc., Stockholder, Chimerix, Inc.