Alicaforsen. Isis Pharmaceuticals.

Abstract

Alicaforsen (ISIS-2302) is an RNase H-dependent antisense inhibitor of the intercellular adhesion molecule ICAM-1 under development by Isis Pharmaceuticals, for the potential treatment of a variety of inflammatory disorders [175741]. As of April 1997 it was in phase III trials for Crohn's disease (CD); however, the trial failed and, in December 1999, the company suspended development for this indication [352801]. In October 2000, the company re-initiated development in CD [384820] and new phase III trials had begin by May 2001 [409704]. In August 2000, phase II studies of alicaforsen in an enema formulation for ulcerative colitis and a topical formulation for psoriasis were ongoing [378715]. Development of the compound for the potential treatment of rheumatoid arthritis (RA) was discontinued in 1999 [347579]. By the end of 1998, alicaforsen was in phase II trials for kidney transplant rejection. At this time, these trials were expected to finish in mid-1999 [343460]. However, they were ongoing in September 1999, although no further development has been reported for this indication since that time [338672]. In February 1995, Isis Pharmaceuticals and Boehringer Ingelheim (BI) signed a collaborative agreement on cell adhesion inhibitors, including alicaforsen [174111]. By early 1999, Isis and BI were to decide on the next developmental step for alicaforsen following further analyses of its performance against CD [292915], [315439]. Their joint development agreement was terminated in 1999; Isis regained rights to the product and by September 1999 was in talks to license alicaforsen to another partner for CD [338672]. In June 2000, Cytogenix entered into a sponsored research agreement with Baylor College of Medicine at the Texas Medical Center Houston for the use of its ssDNA expression system for the development of antisense strategies directed against intercellular adhesion molecules for the purpose of reducing lung inflammation and injury in disease states and conditions [369677]. US-05514788, and other patents, cover antisense cell adhesion molecule inhibitors [212289], [234792].

• Authors: A T Gewirtz, S Sitaraman
• Journal: Current opinion in investigational drugs (London, England : 2000) (Curr Opin Investig Drugs) Vol. 2 Issue 10 Pg. 1401-6 (Oct 2001) ISSN: 1472-4472 [Print] England
• PMID: 11890355 (Publication Type: Journal Article, Review)

Chemical References

• Gastrointestinal Agents
• Immunosuppressive Agents
• Oligodeoxyribonucleotides, Antisense
• Phosphorothioate Oligonucleotides
• Thionucleotides
• alicaforsen

Topics

• Animals
• Arthritis, Rheumatoid (drug therapy)
• Asthma (drug therapy)
• Clinical Trials, Phase I as Topic
• Clinical Trials, Phase II as Topic
• Clinical Trials, Phase III as Topic
• Colitis, Ulcerative (drug therapy)
• Crohn Disease (drug therapy)
• Gastrointestinal Agents (adverse effects, metabolism, pharmacology, therapeutic use, toxicity)
• Graft Rejection (prevention & control)
• Humans
• Immunosuppressive Agents (adverse effects, metabolism, pharmacology, therapeutic use, toxicity)
• Oligodeoxyribonucleotides, Antisense (adverse effects, metabolism, pharmacology, therapeutic use, toxicity)
• Phosphorothioate Oligonucleotides
• Psoriasis (drug therapy)
• Structure-Activity Relationship
• Thionucleotides (adverse effects, metabolism, pharmacology, therapeutic use, toxicity)