NOVEL THERAPEUTIC OPTIONS FOR FAMILIAL HYPERCHOLESTEROLEMIA

Background: Familial Hypercholesterolemia (FH) is an autosomal dominant disorder caused by mutation in the LDL receptor gene and characterized by raised LDL-C, tendon xanthomata and premature atherosclerosis. Existing therapies for FH such as statins and LDL apheresis do not offer adequate lipid control in most patients, which has led to the search for more definite alternatives. Two new drugs have been approved by the US FDA in the recent past for FH, namely mipomersen, an anti-sense oligo-nucleotide and lomitapide, a microsomal triglyceride transfer protein.

Methods: We did a literature search across PubMed to retrieve articles related to efficacy and safety of mipomersen and lomitapide.

Results:Mipomersen has been found to have reasonable efficacy in clinical trials over and above that seen with concomitant statin therapy in FH. Lomitapide has also shown evidence of adequate LDL-C reduction in clinical trials though the number of studies performed with lomitapide is relatively fewer. The subcutaneous route of administration for mipomersen may affect compliance especially with long term treatment.  The most common adverse reactions seen with mipomersen include injection site reactions and flu-like symptoms. Lomitapide has a boxed warning for hepatic steatosis, though there is no evidence so far to indicate that it could progress to hepatic cirrhosis.

Conclusion: Although mipomersen and lomitapide show promise as novel therapeutic options for FH, the long term safety data is definitely warranted before it becomes a front line therapy in FH.