RG7667, a novel combination of two anticytomegalovirus (anti-CMV) monoclonal
IgG1 antibodies (MCMV5322A and MCMV3068A), was designed to block CMV entry into host cells. It was developed as a potential
therapy for preventing CMV
infection and disease in transplant recipients.
RG7667 was assessed for preventing CMV
infection in a phase 2a trial with CMV-seronegative recipients of kidney transplants from CMV-seropositive donors. The patients received 4 intravenous doses of
RG7667 (10 mg/kg of
body weight of each antibody, n = 60) or placebo (n = 60) at the time of the transplant and at 1, 4, and 8 weeks after the transplant. Serum samples were collected for pharmacokinetic (PK) analysis and antidrug antibody (ADA) evaluation. To guide future dose selection, the relationships between
RG7667 exposure and pharmacological activity were evaluated. MCMV5322A and MCMV3068A exposures were confirmed in all RG7667-treated patients. Mean clearances for MCMV5322A and MCMV3068A were 2.97 and 2.65 ml/day/kg, respectively, and the terminal half-lives of MCMV5322A and MCMV3068A were 26.9 and 27.4 days, respectively. The ADA incidence was low and was not associated with lower drug exposure. Patients with
RG7667 or component antibody exposures greater than the respective median values had a lower incidence of
viremia at 12 weeks and 24 weeks after
transplantation and a longer delayed time to detectable CMV
viremia than patients with exposures less than the median values. MCMV5322A and MCMV3068A exhibited expected
IgG1 PK profiles in high-risk kidney transplant recipients, consistent with the earlier PK behavior of
RG7667 in healthy subjects. Higher drug exposure was associated with better anti-CMV pharmacological activity. (This study has been registered at ClinicalTrials.gov under identifier NCT01753167.).