Fomivirsen

Fomivirsen, previously known as ISIS 2922, is an approved second-line treatment for cytomegalovirus (CMV) retinitis that is injected into the eye. Technically, it is known as an antisense oligonucleotide.

When CMV infects a cell, it incorporates part of its genetic material (called the proviral DNA) into the genetic material of the human cell. When the CMV-infected cell reproduces, the proviral DNA is converted into messenger ribonucleic acid (mRNA) and travels out from the cell nucleus to make the proteins from which new virus particles are made. The anti-sense drug is a molecule, which has been carefully designed so that it binds tightly onto part of the mRNA. This means that when the infected cell reproduces, the anti-sense drug prevents the production of the proteins from which new virus particles would be made and so prevents the infection of other cells.

The European Medicines Agency (EMEA) approved fomivirsen for European marketing in April 1999, following United States approval in 1998. Licensed under the trade name Vitravene, fomivirsen is recommended where the standard CMV treatments of ganciclovir (Cymevene) or foscarnet (Foscavir) have failed to prevent the progression of disease or where the patient is intolerant to these drugs.

Fomivirsen was developed by Isis Pharmaceuticals and distributed by Novartis Ophthalmics Europe Ltd. In May 2002, Novartis voluntarily withdrew the marketing authorisation for fomivirsen in Europe for commercial reasons. The drug may be obtained from Novartis in Switzerland on a named-patient basis.

Studies have shown that fomivirsen injected into the eye significantly reduces CMV disease progression. For example, one study compared weekly injections of 165µg fomivirsen for three weeks followed by fortnightly injections, with deferred treatment. The median time to disease progression was 71 days in the treated group compared with 13 days in the untreated group.¹

A number of dosing regimens have been tested in trials. The currently recommended dose is 330µg on days 1 and 15, and monthly injections thereafter.²

Some experts have reservations about the use of fomivirsen due to side-effects which appeared in early clinical trials. Inflammation and spots on the edge of the retina have been cause for concern. However, subsequent trials have found the incidence of these side effects to be low, ranging from four to eight events per patient-year, depending on the intensity of treatment.³

Fomivirsen does not interact with any currently available protease inhibitors or non-nucleoside reverse transcriptase inhibitors (NNRTIs).