Vitravene®

Vitravene Study Group (2002) A randomized controlled chnical trial of intravitreous fomivirsen for treatment of newly diagnosed peripheral cytomegalovirus retinitis in patients with AIDS, Am J Ophthalmol 133 467 74... 

A new antiviral agent, developed for treatment of CMV retinitis, can be administered by intravitreal injection. Formivirsen sodium is a phosphorothioate oligonucleotide that inhibits CMV replication through an antisense mechanism. It is formulated as a sterile and preservative-free solution and supplied in single-use vials (Vitravene ). The product is administered directly into the vitreous cavity posterior to the limbus through a 30-gauge needle. This procedure can be performed on an... 

In August 1998, Vitravene (tradename) became the first (and thus far the only) antisense product to be approved for general medical use by the FDA. It gained approval within the EU the following year, although it has since been withdrawn from the EU market due to commercial rather than technical reasons. The product is a 21-nucleotide phosphorothioate based product of the following base sequence ... 

Developed by the US company, Isis, Vitravene is used to treat cytomegalovirus (CMV) retinitis in AIDS patients. It is synthesized chemically and formulated as a sterile solution (6.6 mg active drug/ml) in WFI using a bicarbonate buffer to maintain a final product pH of 8.7. 

Figure 3.9 Mode of action for antisense drags. An example is Fomivirsen (Vitravene, Isis Pharmaceuticals), which is a 21-nucleotide phosphorothioate that binds to the complementary mRNA of cytomegalovirus and blocks the translation process. Cytomegalovirus is a virus that belongs to the herpes group. (Source Chang YT. Keyword of the Post Genomic Era—Library, New York University, New York, 2002. http //www. nyu.edu/classes/ytchang/book/e003.html [accessed September 10, 2002].)...

Currently, there is only one antisense drug on the market— Vitravene (active ingredient fomivirsen) for the treatment of cytomegalovirus (CMV)-induced retinitis (inflammation of the retina) in AIDS patients. Fomivirsen has 21 nucleotides complementary to a CMV mRNA sequence, which is necessary for the production of infectious virus. Two examples of experimental antisense drugs are provided in Exhibit 3.15, while Table 3.1 lists other antisense drugs in clinical phase. 

Vitravene (Fomivirsen, an antisense ISIS Pharma- Treatment of 1998 (USA)... 

Fomivirsen (Vitravene), an anti-CMV agent, is the first antisense oligonucleotide to be approved by the U. S. Food and Drug Administration (FDA) as an antiviral therapy. Fomivirsen is an oligonucleotide complementary to the major immediate early region 2 (IE2) of CMV mRNA. By binding to IE2 mRNA, fomivirsen prevents its translation to protein and thereby blocks viral replication. Because this mechanism of action is... 

B. Indications and use Intravitreal Vitravene is indicated for local treatment of CMV retinitis in AIDS patients who are refractory to or intolerant of other treatment or when other treatments are contraindicated. 

Dosage form Vitravene is a sterile, aqueous, preservative-free, buffered solution supplied in 0.25 ml single-use vials for intravitreal injection. Each ml of Vitravene solution contains fomivirsen sodium 6.6 mg. 

Recommended dosage and monitoring requirements For the treatment of CMV retinitis in AIDS patients, the recommended dose of Vitravene is 330 pg (0.05 ml) by intravitreal injection for induction, one dose should be injected every other week for two doses for maintenance, after induction, one dose should be given once every 4 weeks after induction. 

Drug interactions Vitravene is not recommended for use in patients who have recently (2-4 weeks) been treated with either intravenous or intravitreal cidofovir because of the risk of exaggerated ocular inflammation. Results from in vitro tests demonstrated no inhibition of anti-CMV activity of fomivirsen by zidovudine or zalcitabine. 

E. Therapeutic response Intravitreal Vitravene therapy is effective in delaying disease progression in AIDS patients with refractory or newly diagnosed CMV retinitis depending on the patient population, the median time to progression has ranged from 2 to 11 weeks. 

G. Other applications The combination of Vitravene and ganciclovir is under investigation for AIDS-related cytomegalovirus... 

The first antisense drug Vitravene has now been approved for the treatment of patients with cytomegalovirus-induced... 

Crooke, S.T. (1998b) Vitravene—another piece in the mosaic. Antisense Nucleic Acid Drug Dev., 8, vii-viii. 

Fomivirsen Vitravene Injected into the eye to treat CMV retinitis... 

Antiviral Efficacy and Clinical Use. Fomivirsen (Vitravene) is injected into the vitreous humour to treat CMV infection in the eye.42 This drug is often used to treat ocular CMV infections that are resistant to more traditional agents such as ganciclovir or fos-carnet. 

Vitravene (fomivirsen, ISIS 2922) Human cytomegalovirus IE-2 gene CMV retinitis Intravitreal Isis/Ciba Vision... 

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