Alicaforsen
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| Synonyms | DNA, d[(R)-P-thio](G-C-C-C-A-A-G-C-T-G-G-C-A-T-C-C-G-T-C-A) |
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| Formula | C192H244N75O98P19S19 |
| Molar mass | 6368.171938 g/mol |
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Alicaforsen is an antisense oligonucleotide therapeutic that targets the messenger RNA for the production of human ICAM-1 protein. It was discovered by Ionis Pharmaceuticals (formerly Isis Pharmaceuticals) and as of 2017 was under development by Atlantic Healthcare for pouchitis in an enema formulation.
ICAM-1 promotes the extravasation and activation of leukocytes (white blood cells), which is part of the inflammation process. Alicaforsen inhibits the activity of ICAM-1 protein by degrading mRNA coding for it via an RNase-H based mechanism.
It appears to have better efficacy as a topical medication than via systemic administration which is typical of antisense drugs.
Alicaforsen is a 20 unit phosphorothioate modified antisense oligonucleotide.
Alicaforsen was discovered and initially developed by Isis Pharamaceuticals, which changed its name to Ionis Pharmaceuticals in 2015.
Isis partnered on development of alicaforsen with Boehringer Ingelheim starting in 1995; that deal ended in 1999, after each of IV and subcutaneously delivered alicaforsen failed in phase III trials for Crohn's disease and development of those formulations in that indication was terminated; development for rheumatoid arthritis was terminated the same year and development in kidney transplant apparently ceased as well at that time.
The company reformulated alicaforsen as an enema and three small trials were published between 2004 and 2006, an open label trial in chronic pouchitis and two randomized trials in ulcerative colitis (UC); in the UC trials the drug missed its primary endpoint of improvements at 6 weeks, but showed a better effect in the longer term (between 18 and 30 weeks).
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