Fomivirsen

Abstract

Fomivirsen (ISIS 2922) is an antisense oligonucleotide which specifically inhibits replication of human cytomegalovirus. It achieves this by binding to complementary sequences on messenger RNA transcribed from the major immediate-early transcriptional unit of the virus. It is being developed for the treatment of cytomegalovirus retinitis. Mean maximum retinal concentrations of fomivirsen occurred approximately 2 days after a single intravitreal injection in monkeys. The elimination half-life of fomivirsen (after a single 115 microg dose) in monkey retina was 78 hours. Fomivirsen, administered as an intravitreal injection, significantly delayed progression of cytomegalovirus retinitis in patients with AIDS in preliminary clinical trials. In 18 patients with newly diagnosed, unilateral, peripheral cytomegalovirus retinitis treated with fomivirsen 165 microg once weekly for 3 weeks, then 165 microg every second week, the median time to disease progression was significantly longer than in 10 patients in whom fomivirsen treatment was deferred until early disease progression (71 vs 14 days). In patients with advanced, refractory, sight-threatening disease, treatment with fomivirsen 330 microg once weekly for 3 weeks and then 330 microg every 2 weeks (n = 34) or 330 microg on days 1 and 15 and then monthly (n = 20) significantly delayed disease progression. The interpolated median time to disease progression was 90 days in both treatment groups. The most common adverse events reported in clinical trials of fomivirsen were increased intraocular pressure and mild to moderate intraocular inflammation. These events were generally transient or reversible with topical steroid treatment.