High-fat diets are all the rage these days, and ACC.17 has some serious high-fat content on the menu for dyslipidemia devotees. Some of the fare available includes the first cardiovascular (CV) outcomes trial data for the PCSK9 inhibitors, new data from a novel approach to targeting PCSK9, and the results of an evaluation of a high-density lipoprotein (HDL) mimetic on coronary atherosclerosis.
First up is a generous double helping of cardiovascular outcomes data for two PCSK9 inhibitors: Amgen’s Repatha (evolocumab) and Pfizer’s (now discontinued) bococizumab. During the opening session of the meeting on Friday March 17, the results of the FOURIER cardiovascular outcomes trial (CVOT) of Repatha will be presented. With Amgen confirming positive top-line results (see press release), all concerned with the PCSK9 class, from patients to payers, will finally get to see just how effective these drugs are on hard endpoints, and if the CV benefits can justify the hefty price tag placed on the drug. In addition, data from the SPIRE CVOTs for Pfizer’s discontinued PCSK9 inhibitor, bococizumab, will follow. Pfizer were forthcoming with the reasons for halting development of the agent (see press release and related DRG blog), citing concerns over immunogenicity, efficacy, and tolerability, but it will be interesting to see the complete picture.
Next to be served up on March 17 is another PCSK9 dish, albeit with a twist. In an afternoon session, the results of the ORION-1 trial, which assessed inclisiran, a small interference RNA compound targeting PCSK9, will be presented. The Medicines Company, developing the drug in collaboration with Alnylam Pharmaceuticals, have already announced that the top-line results for ORION-1 were positive, but there is a general eagerness to see how the actual data compares to that for the PCSK9 inhibitors already on the market. If efficacy and safety are in the same ball park, the extended dosing interval for inclisiran could be a game changer.
After a feast of PCSK9-related research on Friday, Saturday March 18 begins with a little taste of HDL. And then more PCSK9 data. The results from the CARAT study, which evaluated the impact of Cerenis Therapeutics’ HDL mimetic CER-001 on coronary atherosclerosis are to be presented during the first morning session. Although such studies are not as strong as CVOTs, any evidence of regression of atheroma firmly suggests CV benefits are likely. Further food for thought will be provided by the results of the EBBINGHAUS trial, which is evaluating the effect of Repatha on the cognitive state of participants in the FOURIER trial. In 2012, suspicions were raised that statins may impair cognition, but although the weight of evidence now suggests this is not the case, the potent efficacy of the PCSK9 class and possible safety signals in earlier trials of these drugs warranted further investigation, according to the FDA.
On Sunday March 19, a presentation entitled “Early Challenges for PSCK9 Inhibitor Prescriptions and Patients: Rejections and Rates Unfilled” is scheduled. This will hopefully provide some easily digestible insight as to why the much-hyped PCSK9 inhibitors did not see the uptake that was widely expected based on the efficacy demonstrated during Phase III trials. And for dessert, we have further results from STOMP, evaluating atorvastatin’s impact on cognitive function.
Quite a bill of fare for those on a high-fat diet! Bon appétit!!
For further DRG analysis of the Dyslipidemia market click here.