Fomivirsen Approved for CMV Retinitis: First Antisense Drug
On August 27 the U.S. Food and Drug Administration approved the first drug using antisense technology--fomivirsen (Vitravene™) for patients "who are intolerant of or have a contraindication to other treatments for CMV retinitis or who were insufficiently responsive to previous treatments for CMV retinitis." This drug is injected directly into the eye, and is given monthly, except that the first two doses are two weeks apart. The drug was developed by Isis Pharmaceuticals, in cooperation with CIBA Vision, a unit of Novartis AG.Antisense drugs work by blocking a specific gene from producing the protein it codes for. This kind of drug has great potential importance because it can be targeted against only a single gene--either in a virus or other disease-causing organism, or an abnormal human gene. This highly specific action should improve efficacy and reduce side effects. The development of antisense drugs has been slower than some had expected, however, because of technological difficulties such as designing compounds which can readily enter cells.
Fomivirsen was considered on July 22 by an FDA advisory committee (the Ophthalmic Drugs Subcommittee of the Dermatologic and Ophthalmic Drugs Advisory Committee). The subcommittee voted 5-2 for approval, with all the clinicians voting to approve the drug; but there was much concern about the small number of patients in the trials, especially the pivotal study for "first line" use, which compared 18 patients randomly assigned to immediate treatment vs. 10 assigned to deferred treatment. The reason for these small numbers is that the availability of protease inhibitors greatly reduced the incidence of new CMV retinitis, making it very difficult to enroll volunteers into the trial. This small number of patients is probably the reason that the FDA did not grant the additional "first line" approval (for patients previously untreated for CMV retinitis) that the company had requested. There were more volunteers in the studies of fomivirsen for patients who had failed previous treatment for CMV retinitis.
An application to market fomivirsen in Europe is currently being reviewed.
Some information is available at http://www.cibavision.com. Also, the transcript of the FDA advisory committee hearing (on 7/22/98) will probably be placed on http://www.fda.gov, but it is not there as this article goes to press.
