Experience With CMX001, a Novel Antiviral Drug, for Cytomegalovirus infections in Stem Cell Transplant Patients

Cytomegalovirus (CMV) infections are associated with significant morbidity and mortality in the stem cell transplant setting. CMX001, a lipid conjugate of cidofovir is administered orally and circulates as the lipid conjugate in plasma; it is efficiently taken up by target cells and high concentrations of the active antiviral are achieved intracellularly. We describe the first clinical experiences in stem cell transplant patients infected with CMV who received CMX001. The patients had history of AML (3 patients), refractory lymphoma, multiple myeloma, and severe aplastic anemia, and sickle cell anemia. Six of the seven patients had received SCT and the seventh awaited SCT. Treatment with CMX001 was initiated pre-transplant in one patient, and 21 days to greater than 2 years in six patients (median of 61days).We analyzed 7 patients with CMV viremia who were treated under emergency IND because of lack of other reasonable therapeutic options. All 7 patients had failed conventional antiviral therapy: all patients had received ganciclovir and/or valganciclovir, 6 had received foscarnet, and 4 had received CMV IG. The doses of CMX001 in these patients ranged from 80 mg to 300 mg (approximately 2 to 4 mg/kg); follow-up data was available for at least 4 weeks in all patients. Virologic response was defined as more than a 90% reduction (1 log 10) in viral load (VL) and complete response was defined as an undetectable viral load.The 4 males and 3 females treated had a median age of 55 years (range 11 to 69 years); they were treated with CMX001 for a median of 88 days (range 29-131 days). The median reduction in VL was greater than 1.2 log 10 at 4 weeks. A complete response was observed in 3/5 (60%) patients who did not have mutations in the CMV polymerase UL54 gene; 2/5 had an average reduction in CMV by PCR of 1.2 log 10. Neither of two patients with a relevant mutation in UL54 (L501F and A987G) had a 1 log reduction in viremia at the last time point.Two patients had pre-existing renal insufficiency; no dose adjustment was needed based on kidney function. Four of 7 patients had GVHD during treatment with CMX001. One patient experienced C. difficile colitis, one experienced pancytopenia, one with a seizure disorder experienced seizure, and one experienced severe GVHD. No trends were observed in SAEs.This case series demonstrates that CMX001 is a promising therapeutic option for the treatment of CMV disease in stem cell transplant patients. Cytomegalovirus (CMV) infections are associated with significant morbidity and mortality in the stem cell transplant setting. CMX001, a lipid conjugate of cidofovir is administered orally and circulates as the lipid conjugate in plasma; it is efficiently taken up by target cells and high concentrations of the active antiviral are achieved intracellularly. We describe the first clinical experiences in stem cell transplant patients infected with CMV who received CMX001. The patients had history of AML (3 patients), refractory lymphoma, multiple myeloma, and severe aplastic anemia, and sickle cell anemia. Six of the seven patients had received SCT and the seventh awaited SCT. Treatment with CMX001 was initiated pre-transplant in one patient, and 21 days to greater than 2 years in six patients (median of 61days). We analyzed 7 patients with CMV viremia who were treated under emergency IND because of lack of other reasonable therapeutic options. All 7 patients had failed conventional antiviral therapy: all patients had received ganciclovir and/or valganciclovir, 6 had received foscarnet, and 4 had received CMV IG. The doses of CMX001 in these patients ranged from 80 mg to 300 mg (approximately 2 to 4 mg/kg); follow-up data was available for at least 4 weeks in all patients. Virologic response was defined as more than a 90% reduction (1 log 10) in viral load (VL) and complete response was defined as an undetectable viral load. The 4 males and 3 females treated had a median age of 55 years (range 11 to 69 years); they were treated with CMX001 for a median of 88 days (range 29-131 days). The median reduction in VL was greater than 1.2 log 10 at 4 weeks. A complete response was observed in 3/5 (60%) patients who did not have mutations in the CMV polymerase UL54 gene; 2/5 had an average reduction in CMV by PCR of 1.2 log 10. Neither of two patients with a relevant mutation in UL54 (L501F and A987G) had a 1 log reduction in viremia at the last time point. Two patients had pre-existing renal insufficiency; no dose adjustment was needed based on kidney function. Four of 7 patients had GVHD during treatment with CMX001. One patient experienced C. difficile colitis, one experienced pancytopenia, one with a seizure disorder experienced seizure, and one experienced severe GVHD. No trends were observed in SAEs. This case series demonstrates that CMX001 is a promising therapeutic option for the treatment of CMV disease in stem cell transplant patients.