Technology evaluation: fomivirsen, Isis Pharmaceuticals Inc/CIBA vision

Area of Science:

• Oligonucleotide therapeutics
• Antisense technology
• Ophthalmology

Background:

• Cytomegalovirus (CMV) retinitis is a significant opportunistic infection in patients with Acquired Immunodeficiency Syndrome (AIDS).
• Traditional treatments for CMV retinitis often involve systemic administration with potential toxicities.
• The development of targeted therapies is crucial for managing CMV infections in immunocompromised individuals.

Purpose of the Study:

• To introduce fomivirsen (ISIS-2922, Vitravene) as a novel therapeutic agent.
• To highlight its mechanism of action as an antisense oligonucleotide targeting human cytomegalovirus.
• To document its regulatory approval status for CMV retinitis.

Main Methods:

• Fomivirsen is a 21-mer phosphorothioate oligonucleotide designed with sequence complementarity to the major immediate-early gene of human cytomegalovirus.
• It is administered via intravitreal injection, enabling local drug delivery to the affected eye.
• The development and regulatory pathway involved Isis Pharmaceuticals Inc. and marketing by Novartis' CIBA Vision.

Main Results:

• Fomivirsen received FDA marketing approval for the local treatment of CMV retinitis in August 1998.
• It represents the first antisense oligonucleotide to gain regulatory approval for therapeutic use.
• European and Brazilian registration approvals were obtained in the summer of 1999.

Conclusions:

• Fomivirsen (Vitravene) is a pioneering antisense oligonucleotide therapy for CMV retinitis in AIDS patients.
• Its local administration via intravitreal injection offers a targeted approach to treating ocular CMV infections.
• The drug's approval marked a significant advancement in oligonucleotide-based therapeutics.