For an extensive discussion on mipomersen safety and efficacy, see my prior report.
hypercholesterolemia not controlled by maximally tolerated lipid lowering
therapy
R. Santos et al
Background: In randomized, double-blind, phase 3 studies, mipomersen, an antisense
apolipoprotein B synthesis inhibitor, significantly reduced atherogenic lipoprotein levels in familial hypercholesterolemia (FH) patients on maximally tolerated lipid lowering therapy (LLT).
Objective: Evaluate mipomersen’s long-term safety and efficacy in an open-label extension study.
Methods: FH patients on maximally tolerated LLT who had completed a mipomersen phase 3 study received weekly SC mipomersen (98% received 200 mg/week) in this ongoing study.
Results: By the cutoff date, 141 patients had received mipomersen for 0.3 to 32 months
(median=16.4) and 69 had discontinued. Persistent reductions in atherogenic lipoproteins were observed. Liver fat on MRI increased in some patients, but tended to stabilize or decrease with treatment >12 months. Consecutive ALT elevations ≥3xULN ≥7 days apart occurred in 13% of patients, all with no significant bilirubin increases. Conclusions: Mipomersen reduced atherogenic lipoproteins in FH patients not controlled by existing therapies. The safety profile was generally consistent with phase 3 findings. Liver fat increased in some patients, but tended to stabilize or decrease with treatment >12 months. These interim data support mipomersen’s potential long-term use in high-risk FH patients.