Phase III trial of REGN 1500 in homozygous familial hypercholesterolemia published in NEJM.- Regeneron Pharma

Regeneron Pharmaceuticals announced that the New England Journal of Medicine (NEJM) published positive results from the Phase III trial of REGN 1500 (evinacumab) in 65 patients with homozygous familial hypercholesterolemia (HoFH). As initially announced in a topline press release, the trial met its primary endpoint, showing that patients who added evinacumab to other lipid-lowering therapies (n=43) reduced their LDL-C from baseline by 49% compared to lipid-lowering therapies alone (placebo, n=22) at week 24 (47% reduction evinacumab, 2% increase placebo, p<0.0001). at the same time point evinacumab-treated patients also decreased ldl-c from baseline by 132 mg dl compared to placebo 135 mg dl reduction evinacumab 3 mg dl reduction placebo p><0.0001). as discussed in the nejm publication genetic loss of angptl3 has been associated with additional lipid-lowering effects including lowered triglycerides apolipoprotein b apob hdl and non-hdl cholesterol and total cholesterol. evinacumab treatment mirrored these lipid-lowering effects. researchers also assessed in a post hoc analysis the effect of evinacumab in patients with nearly non-existent><2%) ldl-receptor activity whose mean baseline ldl-c levels were 258 mg dl n="10)." among these patients evinacumab reduced ldl-c by 72 from baseline compared to placebo 54 reduction evinacumab 19 increase placebo nominal p="0.005)." during the double-blind treatment period 66 of evinacumab patients and 81 of placebo patients experienced at least one adverse event ae. aes that occurred in at least 5 of patients and more commonly with evinacumab were influenza-like illness 11 evinacumab 0 placebo and rhinorrhea 7 evinacumab 0 placebo. there were no deaths major adverse cardiovascular events or discontinuations due to aes.comment: evinacumab is an investigational medicine that binds to and blocks the function of angiopoietin-like 3 angptl3 and is the first medicine of its kind to show efficacy in patients with hofh including patients with little to no low-density lipoprotein ldl receptor function. patients with hofh have severely elevated levels of bad cholesterol low-density lipoprotein cholesterol or ldl-c which increases their risk for premature atherosclerotic disease and cardiac events as early as their teenage years. treatment guidelines recommend early and intensive ldl-c lowering but patients with hofh are less responsive or unresponsive to standard lipid-lowering therapies including statins and pcsk9 proprotein convertase subtilisin kexin type 9 inhibitors.see: evinacumab for homozygous familial hypercholesterolemia. frederick j. raal et al. n engl j med august 20 2020 383:711-720 doi: 10.1056 nejmoa2004215>