Mipomersen chronicles

Isis Pharmaceuticals Inc. stock rose more than 150% as mipomersen advanced from Phase I to Phase III and the company entered a January 2008 partnership with Genzyme Corp. Since the deal, Isis has fallen 52%, as liver toxicity concerns have emerged from the Phase III data.Last week, Isis (NASDAQ:ISIS) dropped 18% after it announced that the antisense inhibitor of apolipoproteinB-100 (ApoB-100) met the primary endpoint in the Phase III RADICHOL II trial to treat heterozygous familial hypercholesterolemia (heFH), but produced elevated alanine transaminase (ALT) in 12 of 83 patients. The companies did not disclose a timeline for a regulatory submission in heFH, but did say they planned to run an additional trial in the indication.Genzyme (NASDAQ:GENZ) plans to submit regulatory applications in the U.S. and EU in 1H11 for mipomersen to treat homozygous familial hypercholesterolemia (hoFH), a rare form of the disease. In the Phase III RADICHOL I trial reported last year, mipomersen led to abnormal ALT elevations in certain hoFH patients. A. 12/29/03 - Isis starts Phase I testing of mipomersen (formerly ISIS 301012)B. 1/10/05 - Restructures to focus on finding a partner for alicaforsen to treat ulcerative colitis (UC) and developing second-generation antisense candidates, which include mipomersenC. 4/7/06 - Out-licenses mipomersen and two preclinical diabetes compounds to Symphony GenIsis, which was formed by Symphony CapitalD. 4/27/06 - Rises $1.08 (14%) to $8.64 after the company reports initial data showing that low-dose mipomersen reduced ApoB-100, LDL and triglycerides in a Phase II trialE. 11/13/06 - Rises $2.05 (20%) to $12.43 after Isis reports positive data from two Phase II trials of mipomersen to treat hypercholesterolemiaF. 9/13/07 - Says it will exercise its option to acquire Symphony GenIsis, thus reacquiring mipomersenG. 10/4/07 - Two higher doses of mipomersen meet the primary endpoint in a Phase II trial to treat familial hypercholesterolemia...