Fomivirsen - a phosphorothioate oligonucleotide for the treatment of CMV retinitis

Fomivirsen is a 21-nucleotide phosphorothioate oligonucleotide which, when injected into a human eye, is capable of inhibiting CMV retinitis. Its mode of action is consistent with an antisense mechanism. Prior to human trials , fomivirsen was tested in a number of in-vitro cell lines and was found to inhibit CMV replication in a dose-dependent manner with a mean 50% inhibit ory concentration between 0.03 and 0.2 mu M. Intravitreal drug clearance st udies have revealed first-order kinetics with a half-life in the rabbit of 62 hours. In a clinical trial of patients with newly diagnosed CMV retiniti s receiving 165 mu g per injection, time to progression was interpolated to 71 days with 44% of the patients remaining on treatment for over one year. In patients who failed other anti-CMV treatments, the interpolated time to progression was 91 days when receiving 330 mu g per injection. No systemic absorption of the drug could be detected. Reported adverse events have bee n for the most part mild to moderate in intensity and either resolved spont aneously or were treatable with topical medications. Locally administered f omivirsen effectively inhibits CMV retinitis using a mode of action which i s complementary to existing DNA polymerase inhibitors.