The US Food and Drug Administration (FDA) announced yesterday that it has approved Kynamro (mipomersen), an ‘antisense’ drug designed to treat a rare condition that causes the accumulation of extremely high levels of ‘bad’ LDL cholesterol. Antisense drugs are strands of nucleic acid, such as DNA, designed to bind to and inactivate the RNA produced by a given gene.
The approval gives Kynamro, made by Isis Pharmaceuticals of Carlsbad, California, a shot at becoming the first commercially viable antisense drug. Gene silencing via antisense was first described more than 30 years ago and the therapeutic potential of harnessing nucleic acids to shut off targeted genes was immediately apparent. But until now, the only antisense drug to make it to market was Isis’s fomivirsen, a drug for retinitis that was discontinued almost a decade ago because it wasn’t making enough money.
Kynamro’s market will be tiny — for now it is approved only for patients with ‘homozygous familial hypercholesterolaemia’, a severe accumulation of cholesterol that can result in heart attacks before the age of 30 if left untreated. It is unlikely that Kynamro will be used to treat the millions of people with more typical forms of high cholesterol because Kynamro requires weekly injections and carries a risk of liver damage. But Isis Pharmaceuticals has hopes for making the drug profitable even with the small market. Isis has partnered with Genzyme, a firm based in Cambridge, Massachusetts, that is now part of Sanofi and has made its fortune by successfully developing and marketing drugs for rare conditions.
Kynamro works by shutting down the expression of apolipoprotein B100, required for the generation of LDL in the liver. It is considered a ‘second-generation’ antisense drug because it is chemically modified to enhance stability and potency.