Fomivirsen Reasonably Safe, Effective for CMV Retinitis -- HIV/AIDS INFO AND UPDATES

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Date Posted: 12:18:23 05/16/02 Thu
Author: Anonymous
Subject: Fomivirsen Reasonably Safe, Effective for CMV Retinitis

http://www.medscape.com/viewarticle/432629_print

Fomivirsen Reasonably Safe, Effective for CMV Retinitis

Laurie Barclay, MD

MedscapeWire 2002. � 2002 Medscape Portals, Inc
Introduction
NEW YORK (MedscapeWire) Apr 26 ? The antisense oligonucleotide fomivirsen is reasonably safe and effective in treating CMV retinitis in AIDS patients, according to the results of 3 trials by the Vitravene Study Group and an accompanying editorial in the April issue of the American Journal of Ophthalmology.

"Cytomegalovirus (CMV) retinitis is among the most common opportunistic infections in patients with the acquired immunodeficiency syndrome (AIDS)," write D. A. Jabs and P. D. Griffiths, from Johns Hopkins University School of Medicine, Baltimore, Maryland, in an editorial. "There is an ongoing need for treatment options...for patients who develop CMV resistance to initial therapy."

As of September 2001, 4 drugs have been approved by the US Food and Drug Administration (FDA) for the treatment of CMV retinitis: ganciclovir, foscarnet, cidofovir, and fomivirsen. Ganciclovir is available as an intravenous (IV) or oral formulation, as a sustained release implant surgically placed in the eye, and as a prodrug (valganciclovir) with improved gastrointestinal absorption. Foscarnet and cidofovir are available only as IV formulations and fomivirsen only as a formulation for intravitreous injections.

"Although the number of patients treated in any one of these studies is small and although there are problems with both the design and analysis of these studies, these reports give us a better understanding of the drug, its efficacy, and its safety profile," write Jabs and Griffiths.

The first report describes a randomized, controlled clinical trial of fomivirsen 165 �g given weekly for 3 weeks as induction therapy and then every 2 weeks as maintenance therapy to patients with small peripheral CMV retinitis lesions. Compared with patients in the observation group, time to retinitis progression among patients on fomivirsen was longer, and it was similar to that reported with systemically administered agents in other studies of this type.

The second report described 2 clinical trials comparing 2 treatment regimens differing in intensity, but both using a 330 �g dose for patients with relapsed retinitis. Because progression rates were similar, the authors concluded that the 2 regimens were equally effective. "Intravitreous fomivirsen appears to be an effective antiviral agent for arresting CMV replication and halting progression of CMV retinitis among patients whose lesions have reactivated or have been persistently active despite other anti-CMV therapies," they write.

However, the editorialists note that an analysis combining both data sets to evaluate risk factors for progression might have answered questions about the effects of oral ganciclovir and of HAART on the time to retinitis progression and time to treatment failure.

The third article reports the safety profile and adverse effects of fomivirsen used to treat CMV retinitis and demonstrates that "the rates of ocular complications among patients treated with fomivirsen are nontrivial and are dose-dependent," according to Jabs and Griffiths. Approximately 10% of eyes will experience a ''key ocular adverse event'' with each fomivirsen injection. This figure probably underestimates the potential impact of toxicity, in part due to lack of guidelines for evaluation of complications and failure to perform routine visual fields or electroretinography in any of these trials.

The rate of ocular inflammation may be as high as 0.87/person-year for the FDA-approved 330- �g regimen and 1.88/person-year for the more intensive 330-�g regimen. Transient elevation of intraocular pressure occurred at rates of 0.36/person-year for the 330-�g dose given by the less intensive regimen and 1.39/person-year for the 330-�g dose with the more intensive regimen. Rates of retinal detachment were 0.16/person-year for the 165-�g dose, 0.36/person-year for the less-intensive 330-�g regimen, and 0.60/person-year for the more intensive 330-�g regimen.

Although fomivirsen has a more favorable dosing schedule than alternative therapies, the editorialists note that "the ocular toxicity associated with fomivirsen may make this drug a less attractive initial choice," and "it would seem prudent to combine fomivirsen with an oral agent whenever possible.... Nevertheless, clinicians should now be more confident than previously in using fomivirsen in an appropriate setting."

Isis Pharmaceuticals Inc and Novartis Ophthalmics supported these studies.

Am J Ophthalmol. 2002;133(4):467-474, 475-483, 484-498, 552-556

Reviewed by Gary D. Vogin, MD

Laurie Barclay, MD, is a staff writer with WebMD.

MedscapeWire is edited by Deborah Flapan, an associate editor at Medscape. Please send press releases and comments to MedscapeWire@exchange.webmd.net.

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