Regeneron's Evkeeza (evinacumab-dgnb) Receives FDA Approval as First-in-Class Therapy for Homozygous Familial Hypercholesterolemia (HoFH)

2021Year02Month13Daily News/BioValleyBIOON/ --Regeneron (Regeneron) recently announced that the U.S. Food and Drug Administration (FDA) ApprovedEvkeeza（evinacumab-dgnb), as an adjunct to other lipid-lowering therapies, for the treatment of individuals aged ≥12-year-old homozygous familial hypercholesterolemia (HoFH) Pediatric and adult patients. 

Evkeezais a treatmentHoFHa transformative new therapy with a unique mechanism of action, this drug is the United StatesFDAThe first approved targeted therapy that binds to and blocks angiopoietin-like proteins3（ANGPTL3) therapeutic methods for functional restoration,ANGPTL3is a protein that plays a key role in lipid metabolism.

HoFHis an extremely rare genetic disorder of high cholesterol, affecting approximately1300Case patient, characterized by low-density lipoprotein cholesterol (LDL-C, “bad cholesterol”) levels are extremely high, patients are at risk of early-onset atherosclerotic disease and cardiac events as early as adolescence. Treatment guidelines recommend early and intensiveLDL-CDecreased, butHoFHThe patient has a low response (or no response) to standard lipid-lowering therapy, including statins andPCSK9Inhibitor.

EvkeezaCan bind and blockANGPTL3of its function, being the first in its class for therapeutic useHoFHDrugs demonstrating efficacy in patients, including low-density lipoprotein (LDL) patients with little or no receptor function. In2017Year,FDAGrantedevinacumabTreatmentHoFHBreakthrough Therapy Designation for Patients with Hypercholesterolemia (BTD). At the critical3In the phase trial, on top of combined standard lipid-lowering therapy, compared with placebo,EvkeezaTreatment24Zhou JiangLDL-CLevels decreased by nearly half.

RegeneronCenter for Genetics2017in The New England Journal of Medicine (NEJM) published in previous studies found that,ANGPTL3Patients with loss-of-function genetic mutations exhibit significantly reduced levels of key blood lipids, includingLDL-C. By blockingANGPTL3Protein,EvkeezaAimed at replicating the effects of this loss-of-function mutation to reduceHoFHPatient'sLDL-C。

Chair, Department of Genetics, Perelman School of Medicine at the University of PennsylvaniaDaniel J. RaderThe professor stated: “Evkeezais a potential therapyHoFHA Revolutionary New Approach for Patients, ExistingHoFHThe treatment regimen is insufficient for most patients.EvkeezaThrough its unique mechanism of action, it has been proven to reduce various formsHoFHPatient'sLDL-Clevel, even those with barely anyLDLpatients with receptor activity, and represents our controlHoFHPatientLDL-C"Horizontal capabilities have been significantly improved."

President and Chief Scientific Officer, RegeneronGeorge D.YancopoulosThe doctor stated, "EvkeezaYesFDAThe first approvedANGPTL3inhibitor, also the latest example of Regeneron’s development approach, which leverages genetic insights and pioneering technologies to deliver new therapeutic options for patients in need. We are proud to bringEvkeezabring toHoFH“Regeneron expresses its gratitude to the patients and physicians participating in our trial.”

This approval is based on a pivotal3Phase Clinical TrialELIPSE HoFHdata. The trial evaluatedevinacumabTreatmentHoFHEfficacy and Safety in Patients. In the trial,65ExampleHoFHPatients were randomly assigned to2group, one group receiving every4Once-Weekly Intravenous Injectionevinacumab 15mg/kg（n=43) and other lipid-lowering therapies, while the other group received placebo and other lipid-lowering therapies (n=22). At the baseline assessment,evinacumabGroup'sLDL-CThe level is260mg/dL, the placebo group was247mg/dL。evinacumabAlmost all in the group (95%) Patients receiving statin therapy,79%The patient receivedPCSK9Inhibitor therapy. The trial results have been2020Year3the American College of Cardiology Annual Scientific Session held in March (ACC.20) published. (See:ACC.20 - Evinacumab ELipsE HoFH Ph3）

The results showed that the study met its primary endpoint: at week24Zhou,evinacumabcompared with the placebo groupLDL-CLevels significantly decreased from baseline.49%（evinacumabGroup reduction47%, increased in the placebo group2%，p＜0.0001). In addition, during the treatment on day24Zhou,evinacumabMean compared with the placebo groupLDL-CSignificantly Reduced from Baseline132mg/dL（evinacumabDecrease in the group135mg/dL, decreased in the placebo group3mg/dL，p＜0.0001）、LDL-CLevel <100mg/dLof patients was significantly higher (47% vs 23%, nominalp=0.0203）、LDL-CDecrease in level ≥30%a higher proportion of patients (84% vs 19%，p＜0.0001）、LDL-CLevel reduction ≥50%of patients was higher (56% vs 5%，p=0.0003）。 

Furthermore,evinacumabCompared with the placebo group, the treatment group showed differences in other key secondary endpoints, including apolipoproteinB（ApoB), non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol and triglyceride levels were also significantly reduced (p＜0.0001). The same level was also observed in the most difficult-to-treat patientsLDL-Cdecreased; these patients are typically unresponsive to certain other therapies and are referred to as “non-responders”/"Invalid" or "Negative"/"Negative" patients.

As early as the2Zhou,EvkeezaIt was observed thatLDL-Creduction, and throughout the double-blind treatment period (up to24weeks) and the open-label trial period (up to Week48weeks) remain unchanged. (BioValleyBioon.com）

Original Source:FDA approves First-in-class Evkeeza™ (evinacumab-dgnb) for Patients with Ultra-rare Inherited Form of High Cholesterol