Fomivirsen

Fomivirsen (ISIS 2922) is an antisense oligonucleotide which specifically i nhibits replication of human cytomegalovirus. It achieves this by binding t o complementary sequences on messenger RNA transcribed from the major immed iate-early transcriptional unit of the virus. It Is being developed for the treatment of cytomegalovirus retinitis. Mean maximum retinal concentrations of fomivirsen occurred approximate to 2 days after a single intravitreal injection in monkeys. The elimination hal f-life of fomivirsen (after a single 115 mu g dose) in monkey retina was 78 hours. Fomivirsen, administered as an intravitreal injection, significantly delaye d progression of cytomegalovirus retinitis in patients with AIDS in prelimi nary clinical trials. In 18 patients with newly diagnosed, unilateral, peri pheral cytomegalovirus retinitis treated with fomivirsen 165 mu g once week ly for 3 weeks, then 165 mu g every second week, the median time to disease progression was significantly longer than in 10 patients in whom fomivirse n treatment was deferred until early disease progression (71 vs 14 days). In patients with advanced, refractory, sight-threatening disease, treatment with fomivirsen 330 mu g once weekly for 3 weeks and then 330 mu g every 2 weeks (n = 34) or 330 mu g on days 1 and 15 and then monthly (n = 20) sign ificantly delayed disease progression. The interpolated median time to dise ase progression was 90 days in both treatment groups. The most common adverse events reported in clinical trials of fomivirsen we re increased intraocular pressure and mild to moderate intraocular inflamma tion These events were generally transient or reversible with topical stero id treatment.