Amgen is also developing an anti-PCSK9 antibody as a cholesterol-lowering therapeutic
Regeneron and Sanofi are not the only companies looking at PCSK9 as an alternative target for cholesterol-lowering therapeutics: Amgen is also developing an anti-PCSK9 antibody.1
Evolocumab has been evaluated in numerous Phase II and III trials, including a Phase II trial of the antibody as monotherapy in 406 hypercholesterolaemic patients.2
Subjects were given subcutaneous doses of 70, 105 or 140mg or placebo every two weeks, or 280, 350 or 420mg or placebo every four weeks, or 10mg oral ezetimibe daily. The antibody gave a significant reduction in LDL-C on all dose groups, ranging from 39% for the lowest four-weekly dose to 51% in the highest two-weekly group. Placebo gave a 4% reduction, and ezetimibe 15%.
A similar trial was carried out giving evolocumab in the same range and schedule of doses, in combination with a statin to a total of 631 hypercholesterolaemic patients.3 LDL-C reductions on evolocumab ranged from 42% to 66% greater reduction than placebo after 12 weeks.
It has also been evaluated in homozygous familial hypercholesterolaemia.4 Eight patients on stable drug therapy were given 420mg of the antibody every four weeks for at least 12 weeks, followed by the same dose every two weeks for a further 12 weeks. At week 12 the mean change was a 16% reduction in LDL-C, and 14% after the two-week dosing period. There were no serious side-effects.
Phase III trials are now underway, including a study in combination with statins, and another in patients who are intolerant of statin therapy.
1. C.S. Dias et al. J. Am. Coll. Cardiol. 2012, 60, 1888
2. M.J. Koren et al. Lancet 2012, 380, 1995
3. R.P. Giugliano et al. Lancet 2012, 380, 2007
4. E.A. Stein et al. Circulation 2013, 128, 2113