Statins are the most effective treatment to reduce LDL levels and cardiovascular risk, 10-20% of patients are statin intolerant or present adverse effects at high doses (especially muscle damage). Ezetimibe is the alternative drug, though not as effective to reduce LDL, mainly in high risk patients. PSCK9 protein participates in LDL recycling, monoclonal antibody O AMG 145 binds to this protein and increases recycling. This is a phase 2 randomized double blind trial to evaluate AMG 145 vs. ezetimibe and placebo in statin intolerant patients. 160 patients were randomized to 5 arms (to set doses). At 12 weeks follow up, AMG 145 saw a significative reduction in LDL levels compared to the control group. The most frequent adverse effect was mialgia (15,6%) and 4 severe adverse effects were registered.
Conclusion: AMG 145 reduced LDL to levels comparable to those achieved with maximal doses of the most efficacious statins. Combined with ezetimibe, it reduced LDL to < 100 mg/dl in 90% of population.
Comment: Though this drug shows promise, it should be validated in phase 3 studies. Subcutaneous administration could cause adherence, though a 4 week administration seems to compensate this potential problem.
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Evan Stein
2012-11-05
Original title: Goal Achievement after Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects (GAUSS): Interim Results from a Randomized, Double-blind, Placebo-controlled Study