A tiny pain-free jab every two weeks could be the future of cholesterol-lowering for high-risk patients, according to clinical researchers gathered in Amsterdam for the European Society of Cardiology congress.
Eli Roth at the University of Cincinnati said that two companies are currently neck and neck in the race to bring the first PCSK9 antibody to market. Partners Sanofi and Regeneron may have the edge, with Phase III data on their fully human monoclonal antibody alirocumab slated to be presented before the end of the year, while the chief competition comes from Amgen with its antibody AMG 145, said Dr Roth. Both antibodies can be delivered via subcutaneous auto-injectors, which many patients say they prefer to taking daily pills, he added.
Pfizer and Eli Lilly also have mAB PCSK9 inhibitors in Phase II (RN-316 and LY3015014 respectively). Roche’s mAB RG 7652 is on hold whilst the company seeks a partner and Novartis has discontinued their candidate LGT209, said Dr Roth. Other inhibitors targeting PCSK9 via different mechanisms are in Phase I or pre-clinical.
Profound reductions in LDL-C can be achieved by PCSK9 inhibition, for example, alirocumab 150mg has been shown to reduce LDL-C by up to 72% when added to the now off-patent blockbuster Lipitor (atorvastatin) said Dr Roth. The mAB PCSK9 inhibitors "appear to be extremely safe – it is difficult to tell the difference between patients on active compound and those on placebo,” he claimed, stating that "this is the first impressive lipid therapy we have had since the discovery of statins thirty years ago”.
The level of investment in Phase III programmes for both front runners is eye-watering. In their ODYSSEY Programme for alirocumab, Sanofi and Regeneron have 12 global trials including more than 23,500 patients across 2,000 study centres – and Amgen have a similar number of patients recruited in its FOURIER outcome study.
Asked if this level of investment represented a gamble, Jay Edelberg, head of PCSK9 development at Sanofi's operations in Bridgewater, USA, told Pharma Times that alirocumab is a top priority for both his firm and Regeneron. “Alirocumab showed unparalled efficacy in Phase II. We are looking forward to the first Phase III results later this year. This will come from our monotherapy study and will help shape our dosing strategy. These are incredibly exciting times,” he said.
By inhibiting PCSK9 (proprotein convertase subtilisin kexin type 9) these agents increase the number of LDL receptors on liver cells thereby boosting LDL clearance from the blood. With up to eight out of ten high risk patients not reaching their cholesterol treatment goal using statin therapy, new treatments are needed, said Alberico Catapano of the University of Milan.