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.