Kynamro (mipomersen sodium)
The following drug information is obtained from various newswires, published
medical journal articles, and medical conference presentations.
homozygous familial hypercholesterolemia
General Information
Kynamro (mipomersen sodium) inhibits the ApoB-100 molecule, a protein that plays a pivotal role in the production of low-density lipoprotein (LDL). It reduces LDL-C by preventing the formation of atherogenic lipoproteins, the particles that carry cholesterol through the bloodstream.
Kynamro is specifically indicated as an adjunct to lipid-lowering medications and diet to reduce low density lipoprotein-cholesterol (LDL-C), apolipoprotein B (apo B), total cholesterol 31 (TC), and non-high density lipoprotein-cholesterol (non-HDL-C) in patients with homozygous familial hypercholesterolemia (HoFH).
Kynamro is supplied as a solution for subcutaneous injection. The recommended dose is 200 milligrams (mg) once weekly.
Clinical Results
FDA Approval
The FDA approval of Kynamro was based on a multinational, randomized placebo controlled, 26-week trial in 51 subjects with HoFH. Kynamro was given as 200 mg weekly subcutaneous injections, as an adjunct to lipid-lowering medications. The primary efficacy endpoint was percent change in LDL-C from baseline to Week 28. At Week 28, the mean and median percent changes in LDL-C from baseline were -25% (p<0.001) and -19%, respectively, for the Kynamro group. The mean and median treatment difference from placebo was -21% and -19%, respectively.
Side Effects
Adverse events associated with the use of Kynamro may include, but are not limited to, the following:
- injection site reactions
- flu-like symptoms
- nausea
- headache
- elevations in serum transaminases
Mechanism of Action
Mipomersen is an antisense oligonucleotide targeted to human messenger ribonucleic acid (mRNA) for apo B-100, the principal apolipoprotein of LDL and its metabolic precursor, VLDL. Mipomersen is complementary to the coding region of the mRNA for apo B-100, and binds by Watson and Crick base pairing. The hybridization of mipomersen to the cognate mRNA results in RNase H-mediated degradation of the cognate mRNA thus inhibiting translation of the apo B-100 protein.
Literature References
McGowan MP, Tardif JC, Ceska R, Burgess LJ, Soran H, Gouni-Berthold I, Wagener G, Chasan-Taber S Randomized, placebo-controlled trial of mipomersen in patients with severe hypercholesterolemia receiving maximally tolerated lipid-lowering therapy. Public Library of Science one PLoS 1 2012;7(11):e49006. doi: 10.1371/journal.pone.0049006. Epub 2012 Nov 13.
Raal FJ, Santos RD, Blom DJ, Marais AD, Charng MJ, Cromwell WC, Lachmann RH, Gaudet D, Tan JL, Chasan-Taber S, Tribble DL, Flaim JD, Crooke ST Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: a randomised, double-blind, placebo-controlled trial. Lancet 2010 Mar 20;375(9719):998-1006
Additional Information
For additional information regarding Kynamro or homozygous familial hypercholesterolemia, please visit the Kynamro web page.