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>