Amgen’s cholesterol-lowering antibody evolocumab met its objectives in a phase III trial, setting the company up for a race to market with rivals including Sanofi/Regeneron and Pfizer.
Evolocumab (formerly AMG 145) reduces low-density lipoprotein cholesterol (LDL-c) by targeting PCSK9 (proprotein convertase subtilisin/kexin type 9), an enzyme involved in cholesterol synthesis.
Like other drugs in the class Amgen is positioning it as an alternative to statins in patients with stubbornly high cholesterol levels.
In the 614-patient MENDEL-2 trial subcutaneous doses of the drug, given once every two weeks or monthly, significantly lowered LDL-c levels from baseline after 10 and 12 weeks of treatment.
The reductions seen with the drug were better than those achieved with either placebo or Merck & Co’s Zetia (ezetimibe), and consistent with the results seen in phase II trials, said Amgen.
In the phase II trials, twice-monthly treatment with the antibody cut LDL-c levels by around 50 per cent, while ezetimibe managed only a 15 per cent reduction.
Specific details of the phase III results have not been disclosed but will be presented at a medical conference in the coming weeks, according to the company, which notes that a significant proportion of patients with elevated cholesterol cannot meet treatment targets using statins alone.
News that the results were positive sets up an interesting battle between Amgen and Regeneron/Sanofi – whose alocirumab (REGN727) candidate produced impressive results in a phase III trial reported in October – and Pfizer which recently started a phase III programme for its bococizumab (RN-316) drug.
One of the major questions for the PCSK9 class as a whole is whether regulators will approve them based on biomarkers such as LDL-c or insist that developers have cardiovascular outcomes data. A number of studies have started to question the validity of LDL-c as a surrogate marker for cardiovascular risk.
Evolocumab is currently in the 22,500-patient FOURIER study, which is investigating adding the drug to placebo or statin therapy in patients with established cardiovascular disease and is due to generate results in early 2018.
Meanwhile, Amgen has four other phase III trials ongoing, including the 950-patient GLAGOV trial that will use ultrasound to see if it can reduce the size of atherosclerotic plaques. Results from the study should be available in the middle of 2015.
Cardiovascular medicine is a fairly new area for Amgen, although it should have time to build some momentum in this area following its acquisition of the rights to heart failure treatment Procoralan (ivabradine) from Servier in July.
That could be particularly important as it is expected that PCSK9 inhibitors will – initially at least – be most likely prescribed by cardiology specialists rather than primary care physicians.