News, literature and expert perspectives on PCSK9 inhibition
In ODYSSEY trials, LDL-lowering and adverse events were not different between patients with and without antidrug antibodies against PCSK9 antibody alirocumab.
ACC 2017 No difference in cognitive function was seen between evolocumab and placebo-treated patients in the EBBINGHAUS trial. No cognitive decline was seen over time in either treatment group.
ACC 2017 Dr. Paul Ridker discusses data of the SPIRE studies into use of the PCSK9 antibody bococizumab, including the unexpected attenuation of the LDL-c response over time in some patients, as a consequence of development of antibodies against the drug.
ACC 2017 Inclisiran, which prevents PCSK9 protein production, resulted in long-term LDL-c lowering after two doses of siRNA, without safety concerns, in the ORION-1 study.
ACC 2017 Marc S. Sabatine (Boston) presented the FOURIER-study, which evaluated a PCSK9 inhibitor during two years in over 27000 high-risk patients. LDL-c was reduced by 59%. Both the primary and the secundary clinical endpoint were significantly reduced.
ACC 2017 The SPIRE trial data show that treatment with bococizumab resulted in LDL-c lowering that was not stable over time, due to generation of anti-drug antibodies.
ACC 2017 The FOURIER trial showed stable LDL-c reduction with evolocumab during 3 years in statin-treated CVD patients, and lower CV event rates. Event curves continued to diverge over time.
A pooled analysis of data of more than 6000 patients in 12 parent and extension trials, with a median exposure of 2.8 and 11.1 months, respectively, confirmed the safety and tolerability of evolocumab.
Interim analysis of the largest and longest study of lipid-lowering therapy in HoFH patients to date supports the long-term tolerability and safety of evolocumab, with or without concomitant LDL apheresis.
Circulating monocytes of FH patients not on statins showed a pro-inflammatory phenotype and intracellular lipid accumulation, which was reversed upon treatment with PCSK9 antibodies.
In a meta-analysis with more than 5 000 patients with a median alirocumab exposure of 1.5 years, low levels of LDL-C (<25 mg/dl) were associated with an increased incidence of cataracts.
Alirocumab treatment of healthy volunteers reduced LDL-C and LDL-apoB concentrations and doubled the efficiency with which LDL particles were removed from the circulation.