Alicaforsen


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 and as of 2017 was under development by Atlantic Healthcare for pouchitis in an enema formulation.

Pharmacology

ICAM-1 promotes the extravasation and activation of leukocytes, 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.

Clinical trials

The results of testing alicaforsen in Crohn's disease have largely been negative.

Chemistry

Alicaforsen is a 20 unit phosphorothioate modified antisense oligonucleotide.

History

Alicaforsen was discovered and initially developed by Isis Pharmaceuticals, 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 ; in the UC trials the drug missed its primary endpoint of improvements at 6 weeks, but showed a better effect in the longer term.
Alicaforsen was licensed to Atlantic Healthcare in 2007.
The use of the enema formulation of alicaforsen to treat pouchitis was granted orphan drug status in the US in 2008 and received the same in Europe in 2009. The enema formulation of alicaforsen for pouchitis received FDA Fast Track designation. However, in a subsequent Phase 3 clinical trial, the co-primary endpoints in the primary analysis were not met.