Fomivirsen

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Fomivirsen
Fomivirsen composite.png
Clinical data
AHFS/Drugs.com Micromedex Detailed Consumer Information
Pregnancy
category
Routes of
administration
Intravitreal injection
ATC code
Legal status
Legal status
  • Withdrawn
Identifiers
CAS Number
ChemSpider
  • none
KEGG
ChEMBL
Chemical and physical data
Formula C204H263N63O114P20S20
Molar mass 6682.4 g/mol
 NYesY (what is this?)  (verify)

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]

It was discovered at the NIH and was licensed and initially developed by Isis Pharmacueticals, 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Novartis withdrew the marketing authorization in the EU in 2002[4] and in the US in 2006.[5] The drug was withdrawn because while there was a high unmet need for drugs to treat CMV when the drug was initially discovered and developed due to the CMV arising in people with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[edit]

  1. ^ Katzung, Bertram G. (2006). Basic and Clinical Pharmacology (10th ed.). New York: McGraw-Hill Medical Publishing Division. p. 817. ISBN 0-07-145153-6. 
  2. ^ a b Bubela, Tania; McCabe, Christopher (21 July 2014). "Value-Engineered Translation: Developing Biotherapeutics That Align With Health-System Needs". American Journal of Managed Care. 
  3. ^ Jiang, Kevin (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)". Antimicrob. Agents Chemother. 42 (4): 971–3. PMC 105584Freely accessible. 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[edit]

  • Grillone, LR; Lanz, R (2001). "Fomivirsen". Drugs Today (Barc). 37 (4): 245–255. PMID 12768225. 
  • Geary R, Henry S, Grillone L (2002). "Fomivirsen: clinical pharmacology and potential drug interactions". Clin Pharmacokinet. 41 (4): 255–60. doi:10.2165/00003088-200241040-00002. PMID 11978144. 
  • Vitravene Study, Group (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". Am J Ophthalmol. 133 (4): 475–83. doi:10.1016/S0002-9394(02)01326-0. PMID 11931781. 
  • Roehr B (1998). "Fomivirsen approved for CMV retinitis". J Int Assoc Physicians AIDS Care. 4 (10): 14–6. PMID 11365956. 

External links[edit]