Purpose of review: Mipomersen has been approved by the US Food and Drug Administration as an orphan drug for patients with homozygous familial hypercholesterolemia (HoFH). In contrast, the European Medicines Agency advised negatively on the use of mipomersen. In this review, we discuss the efficacy and safety considerations for this discrepancy. Recent findings: On the basis of the results of clinical trials with mipomersen, safety concerns have been raised regarding cardiovascular risk reduction and development of hepatic steatosis. In addition, (long-term) tolerability concerns have been raised predominantly regarding injection site reactions. A pooled analysis of cardiovascular events in phase III trials with mipomersen did not provide evidence for either a positive or negative effect on cardiovascular disease. Although long-term studies with mipomersen are eagerly awaited, hepatic fat content appears to stabilize after 6-12 months notwithstanding continued mipomersen administration. Summary: HoFH is a disease with an unmet medical need for new lipid-lowering therapies. On the basis of a mean 2.9 mmol/l LDL-cholesterol reduction, mipomersen is expected to reduce cardiovascular risk in HoFH. Available evidence suggests that the fat accumulation associated with this treatment differs from steatohepatitis, which is a progressive and damaging liver disease. No evidence is available suggesting that injection site reactions because of mipomersen treatment will result in safety issues.

Additional Metadata
Keywords alanine aminotransferase blood level, cardiometabolic risk, cardiovascular disease, cardiovascular risk, cerebrovascular accident, drug efficacy, drug mechanism, drug safety, drug tolerability, drug withdrawal, familial hypercholesterolemia, fat content, fatty liver, flu like syndrome, follow up, heart infarction, hematoma, homozygous familial hypercholesterolemia, human, inflammation, injection site erythema, injection site pain, injection site reaction, lipid storage, liver disease, multiple sclerosis, nonhuman, patient compliance, priority journal, quality of life, review, rheumatoid arthritis, risk reduction, side effect, skin discoloration
Persistent URL dx.doi.org/10.1097/MOL.0b013e328362dfd9, hdl.handle.net/1765/41261
Journal Current Opinion in Lipidology
Sjouke, B, Balak, D.M.W, Beuers, U, Ratziu, V, & Stroes, E.S.G. (2013). Is mipomersen ready for clinical implementation? A transatlantic dilemma. Current Opinion in Lipidology (Vol. 24, pp. 301–306). doi:10.1097/MOL.0b013e328362dfd9