At this year’s European Society of Cardiology (ESC) Congress, Amgen presented positive results from the HUYGENS Phase III trial of Repatha (evolocumab), providing insight into the drug’s ability to improve plaque stability in coronary artery disease patients. Specifically, the trial set out to research the effects of the PCSK9 inhibitor on fibrous cap thickness (FCT) in non-ST-elevation acute coronary syndrome (ACS) patients on maximally tolerated statin therapy. The positive data from the HUYGENS study will help highlight and drive increasing confidence in Repatha’s capability to treat patients with established cardiovascular disease in order to reduce the risk of cardiovascular events such as myocardial infarction.
It has been observed that aggressive lipid-lowering therapy with statins in ACS patients has been associated with increased FCT, but the effect on plaque when adding a PCSK9 inhibitor to statin therapy requires additional research. Key opinion leaders interviewed by GlobalData noted that an ideal lipid-lowering drug would not only reduce lipids, but would also have an effect on the fibrous cap of the plaque.
The HUYGENS study, which enrolled 164 patients, showed that once-monthly subcutaneous Repatha treatment in patients who were already on maximally tolerated statin therapy resulted in a benefit in ACS patients by helping to maintain FCT. The study found that Repatha plus maximally tolerated statin therapy was successful in significantly improving plaque stability, meeting its primary endpoint by increasing FCT by 42.7um compared to 21.5um resulting from maximally tolerated statin therapy alone (p=0.01), as measured by optical coherence tomography (OCT).
There is also a Phase IV study, ALTAIR , which is investigating the stabilising effect of another PCSK9 inhibitor, Sanofi and Regeneron ’s Praluent (alirocumab), on vulnerable plaque in coronary artery disease. The trial is comparing Praluent subcutaneous injection every two weeks plus stain therapy with statin therapy alone. The smaller number of patients in each of the studies, HUYGENS and ALTAIR, will likely serve as a barrier to fully understanding and appreciating the effects of PCSK9 inhibitors on FCT. Despite this, FCT changes brought on by the use of PCSK9 inhibitors remains an area of great interest to developers that are invested in this increasingly competitive market.