Curr Opin Invest Dr
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Isis and Merck are developing an antisense oligonucleotide for the potential treatment of hepatitis C virus (HCV) infection [305306]. As of March 2000, the lead from this program, ISI-14803, was being studied in a phase I/II trial where it was administered in three weekly 2-h infusions for 4 weeks [327913], [357823]. ⋯ In January 2000, Isis signed a binding letter of agreement with Elan to form a new subsidiary of Isis to develop ISIS-14803 [351881], [362727]. In October 2001, Isis reported that it had earned a $1.5 million research milestone payment from Merck for progress in this collaboration [426015].
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Hepatitis C virus (HCV) infection is a major health crisis worldwide. Current treatment requires combination therapy with interferon-alpha and ribavirin. The low efficacy and poor tolerability of this therapeutic regimen has driven the search for safer and more effective medicines. ⋯ At the same time, efforts have been directed towards improving the efficacy and tolerability of existing therapies. Recent developments in the area of modified interferons and research on virus-encoded and host drug discovery targets are reviewed here. Advances in the field of improved interferon-based treatments and the use of new antiviral agents in clinical trials gives cause for optimism in the clinical management of HCV infections.
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ISIS-3521 is a 20-mer antisense phosphorothioate oligonucleotide PKCa expression inhibitor, under development by Isis (formerly in collaboration with Novartis) for the potential treatment of solid tumors that are refractory to, or recurrent with, standard treatment regimens [175741]. In November 1999, Novartis announced that it would end its codevelopment of ISIS-3521 [348221], [348222]. In August 2001, Eli Lilly in-licensed ISIS-3521 [420062]. ⋯ In April 2001, Bear Sterns & Co predicted US approval of ISIS-3521 in 2002 [411081]. In August 2001, Eli Lilly and Isis entered into a four-year strategic alliance that includes ISIS-3521. For the license of ISIS-3521, Isis will receive $25 million in upfront fees and will be reimbursed for remaining phase III development and registration costs [420062].
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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]. ⋯ 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].
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Curr Opin Invest Dr · Sep 2001
ReviewDevelopment of CGRP antagonists for the treatment of migraine.
Migraine is one of the most common neurological disorders, involving periodical attacks of headache and nausea as well as a plethora of other symptoms. Although considerable progress has been made, the pathophysiology of migraine is still not understood. However, several observations point to an involvement of calcitonin gene-related peptide (CGRP). ⋯ CGRP is localized to neurons in the trigeminal ganglia and CGRP levels are increased during a migraine attack, presumably causing the vasodilation observed. Accordingly, it is conceivable that inhibition of CGRP-evoked dilatation of the cranial vessels may provide a novel treatment for migraine headache. The non-peptidic CGRP antagonist BIBN-4096BS (Boehringer Ingelheim) is presently under clinical investigation to assess the importance of CGRP in migraine headache and to answer the question of whether the concept of CGRP antagonists may offer advantages, e.g., higher efficacy, lower recurrence rate or improved side-effect profile, compared to the currently used antimigraine drugs.