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Alicaforsen. Isis Pharmaceuticals.

A T Gewirtz1, S Sitaraman

  • 1Emory University School of Medicine, Department of Pathology and Laboratory Medicine, Atlanta, GA 30322, USA. agewirt@emory.edu

Current Opinion in Investigational Drugs (London, England : 2000)
|March 14, 2002
PubMed
Summary

Alicaforsen, an antisense inhibitor of ICAM-1, was developed for inflammatory disorders. Despite setbacks in Crohn

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Area of Science:

  • Pharmacology and Therapeutics
  • Molecular Biology
  • Immunology

Background:

  • Alicaforsen (ISIS-2302) is an RNase H-dependent antisense inhibitor targeting intercellular adhesion molecule 1 (ICAM-1).
  • It was investigated for various inflammatory conditions, including Crohn's disease, ulcerative colitis, psoriasis, rheumatoid arthritis, and kidney transplant rejection.
  • Development involved collaborations and strategic partnerships, with shifting focus and indications over time.

Purpose of the Study:

  • To evaluate the efficacy and safety of alicaforsen in treating inflammatory disorders.
  • To explore alicaforsen's potential in different therapeutic areas through various clinical trial phases.
  • To assess the viability of antisense technology for managing inflammatory conditions.

Main Methods:

  • Antisense oligonucleotide therapy targeting ICAM-1.
  • Clinical trials (Phase II and III) were conducted for different indications.
  • Formulations included enema and topical applications.

Main Results:

  • Development for Crohn's disease faced initial setbacks but was later re-initiated.
  • Trials for ulcerative colitis and psoriasis were ongoing in Phase II.
  • Development for rheumatoid arthritis was discontinued, and kidney transplant rejection trials showed no further reported development after Phase II.
  • Collaborative agreements influenced development, with Isis Pharmaceuticals eventually regaining full rights.

Conclusions:

  • Alicaforsen demonstrated potential as an antisense inhibitor for inflammatory conditions.
  • The development pathway was complex, marked by trial outcomes, strategic decisions, and partnerships.
  • Further research and development were pursued for specific indications like Crohn's disease.

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