Fomivirsen

Fomivirsen (brand name Vitravene) is an antisense antiviral drug that was used in the treatment of cytomegalovirus retinitis (CMV) in immunocompromised patients, including those with AIDS. It was administered via intraocular injection.[1]

Fomivirsen
Clinical data
AHFS/Drugs.comMicromedex Detailed Consumer Information
Pregnancy
category
    Routes of
    administration    		Intravitreal injection
    ATC code
    Legal status
    Legal status
    • Withdrawn
    Identifiers
    CAS Number
    DrugBank
    ChemSpider
    • none
    KEGG
    ChEMBL
    Chemical and physical data
    FormulaC204H263N63O114P20S20
    Molar mass6682.4 g/mol g·mol−1
     NY (what is this?)  (verify)

    It was discovered at the NIH and was licensed and initially developed by Isis Pharmaceuticals, which subsequently licensed it to Novartis.[2] It was licensed by the FDA for CMV in Aug 1998, and was the first antisense drug that was approved.[3]

    Novartis withdrew the marketing authorization in the EU in 2002[4] and in the US in 2006.[5] The drug was withdrawn because while there was a high unmet need for drugs to treat CMV when the drug was initially discovered and developed due to the CMV arising in people with AIDS, the development of HAART dramatically reduced the number of cases of CMV.[2]

    It is an antisense oligonucleotide -- a synthetic 21 member oligonucleotide with phosphorothioate linkages (which are resistant to degradation by nucleases) and has the sequence:

    • 5'-GCG TTT GCT CTT CTT CTT GCG-3'

    [6] It blocks translation of viral mRNA by binding to the complementary sequence of the mRNA transcribed from the template segment of a key CMV gene UL123, which encodes the CMV protein IE2. It was the first antisense antiviral approved by the FDA.[7]

    References
    1. Katzung BG (2006). Basic and Clinical Pharmacology (10th ed.). New York: McGraw-Hill Medical Publishing Division. p. 817. ISBN 978-0-07-145153-6.
    2. Bubela T; McCabe C (July 2014). "Value-engineered translation: developing biotherapeutics that align with health-system needs". The American Journal of Managed Care. 20 (10 Spec No): E3. PMID 25830190.
    3. Jiang K (February 19, 2013). "Biotech comes to its 'antisenses' after hard-won drug approval : Spoonful of Medicine". Nature Medicine: Spoonful of Medicine Blog.
    4. "Public Statement on Vitravene (fomiversen): Withdrawal of the Marketing Authorization in the European Union" (PDF). EMA. August 6, 2002.
    5. "Initiating Coverage: Rexahn Pharmaceuticals (RNN)" (PDF). LifeSci Capital. May 23, 2016.
    6. Mulamba GB, Hu A, Azad RF, Anderson KP, Coen DM (April 1998). "Human cytomegalovirus mutant with sequence-dependent resistance to the phosphorothioate oligonucleotide fomivirsen (ISIS 2922)". Antimicrobial Agents and Chemotherapy. 42 (4): 971–3. doi:10.1128/AAC.42.4.971. PMC 105584. PMID 9559825.
    7. Roush W (May 1997). "Antisense aims for a renaissance". Science. 276 (5316): 1192–3. doi:10.1126/science.276.5316.1192. PMID 9182327.

    Further reading
    • Grillone LR, Lanz R (April 2001). "Fomivirsen". Drugs of Today. 37 (4): 245–255. doi:10.1358/dot.2001.37.4.620590. PMID 12768225.
    • Geary RS, Henry SP, Grillone LR (2002). "Fomivirsen: clinical pharmacology and potential drug interactions". Clinical Pharmacokinetics. 41 (4): 255–60. doi:10.2165/00003088-200241040-00002. PMID 11978144.
    • Vitravene Study Group (April 2002). "Randomized dose-comparison studies of intravitreous fomivirsen for treatment of cytomegalovirus retinitis that has reactivated or is persistently active despite other therapies in patients with AIDS". American Journal of Ophthalmology. 133 (4): 475–83. doi:10.1016/S0002-9394(02)01326-0. PMID 11931781.
    • Roehr B (October 1998). "Fomivirsen approved for CMV retinitis". Journal of the International Association of Physicians in AIDS Care. 4 (10): 14–6. PMID 11365956.
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