Fomivirsen

Fomivirsen
Clinical data
AHFS/Drugs.comMicromedex Detailed Consumer Information
Pregnancy
category
  • AU: B2
Routes of
administration		Intravitreal injection
ATC code
Legal status
Legal status
  • Withdrawn
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC204H263N63O114P20S20
Molar mass6682.35 g·mol−1
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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 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Novartis withdrew the marketing authorization in the EU in 2002[4] and in the US in 2006.[5] The drug was withdrawn because while there was a high unmet need for drugs to treat CMV when the drug was initially discovered and developed due to the CMV arising in people with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]

  1. ^ Trevor AJ, Katzung BG, Knuidering-Hall M, Masters S (2012). Katzung & Trevor's Pharmacology (10th ed.). New York: McGraw-Hill Medical Publishing Division. p. 429. ISBN 978-0-07-178923-3.
  2. ^ a b 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. Archived from the original on 2017-09-29. Retrieved 2017-01-02.
  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. Archived from the original (PDF) on May 23, 2018. Retrieved January 2, 2017.
  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): 971–973. doi:10.1128/AAC.42.4.971. PMC 105584. PMID 9559825.
  7. ^ Roush W (May 1997). "Antisense aims for a renaissance". Science. 276 (5316): 1192–1193. doi:10.1126/science.276.5316.1192. PMID 9182327. S2CID 6983051.