General Information

Evkeeza (evinacumab-dgnb) is an ANGPTL3 (angiopoietin-like 3) inhibitor.

Evkeeza is specifically indicated as an adjunct to other low-density lipoprotein-cholesterol (LDL-C) lowering therapies for the treatment of adult and pediatric patients, aged 12 years and older, with homozygous familial hypercholesterolemia (HoFH).

Evkeeza is supplied as a solution for intravenous administration. The recommended dose of Evkeeza is 15 mg/kg administered by intravenous (IV) infusion over 60 minutes once monthly (every 4 weeks). If a dose of Evkeeza is missed, administer as soon as possible. Thereafter, Evkeeza should be scheduled monthly from the date of the last dose. Assess LDL-C when clinically appropriate. The LDL-lowering effect of Evkeeza may be measured as early as 2 weeks after initiation.

Mechanism of Action

Evkeeza (evinacumab-dgnb) is a recombinant human monoclonal antibody that binds to and inhibits ANGPTL3. ANGPTL3 is a member of the angiopoietin-like protein family that is expressed primarily in the liver and plays a role in the regulation of lipid metabolism by inhibiting lipoprotein lipase (LPL) and endothelial lipase (EL). Evinacumab-dgnb inhibition of ANGPTL3 leads to reduction in LDL-C, HDL-C, and triglycerides (TG). Evinacumab-dgnb reduces LDL-C independent of the presence of LDL receptor (LDLR) by promoting very low-density lipoprotein (VLDL) processing and clearance upstream of LDL formation. Evinacumab-dgnb blockade of ANGPTL3 lowers TG and HDL-C by rescuing LPL and EL activities, respectively.

Clinical Trial Results

The FDA approval of Evkeeza was based on ELIPSE HoFH, a Phase 3 randomized, double-blind, placebo-controlled, parallel-group trial evaluating the efficacy and safety of evinacumab 15 mg/kg administered intravenously every four weeks in 65 patients aged 12 years or older with HoFH. The primary endpoint was reduction of LDL cholesterol after 24 weeks. Results from the evinacumab group at week 24 included a 49% reduction in LDL cholesterol from baseline, compared to placebo (47% reduction for evinacumab compared to a 2% increase for placebo, meeting the primary endpoint. Secondary endpoints were also reached: evinacumab treated patients had a 132 mg/dL absolute change in LDL cholesterol from baseline, compared to placebo (135 mg/dL reduction for evinacumab compared to a 3 mg/dL reduction for placebo and 47% of patients in the evinacumab arm achieved LDL cholesterol levels less than 100 mg/dL, compared to 23% for placebo. Similar levels of LDL cholesterol-lowering were also observed in the most difficult-to-treat patients who often don't respond to certain other therapies, described as "null/null" or "negative/negative" patients. Evinacumab also reduced apolipoprotein B (ApoB), non-HDL cholesterol and total cholesterol compared to placebo.