- ACRONYMS AND DEFINITIONS
- AHA - American Heart Association
- ANGPTL3 - Angiopoietin-like protein 3
- HoFH - Homozygous familial hypercholesterolemia
- DRUGS IN CLASS
- Angiopoietin-like protein 3 (ANGPTL3) inhibitors
- Evinacumab (Evkeeza®)
- FDA-APPROVED INDICATIONS
- Homozygous familial hypercholesterolemia (HoFH) - 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)
- MECHANISM OF ACTION
- Angiopoietin-like protein 3 (ANGPTL3) inhibitor
- 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.
- EFFECTIVENESS
| Effects of Evinacumab at 24 Weeks on Lipid Parameters in Patients with HoFH on Maximally Tolerated Lipid-lowering Therapy | ||
|---|---|---|
| Parameter (average baseline value) |
Evinacumab 15 mg/kg every 4 weeks (N=43) |
Placebo (N=22) |
| Total (322 mg/dl) |
-47% | +1% |
| LDL (255 mg/dl) |
-47% | +2% |
| HDL (44 mg/dl) |
-30% | +1% |
| Triglycerides (124 mg/dl) |
-55% | -5% |
| Apo B | -41% | -5% |
- Professional recommendations
- Evinacumab was FDA-approved in 2021. It has not been incorporated into any guidelines yet.
- See cholesterol treatment guidelines for recommendations from various professional organizations
- SIDE EFFECTS
| Evinacumab side effects from trials lasting 24 weeks | ||
|---|---|---|
| Side effect | Evinacumab (N=81) |
Placebo (N=54) |
| Nasopharyngitis | 16% | 13% |
| Infusion reactions ✝ | 7% | 4% |
| Influenza-like illness | 7% | 6% |
| Dizziness | 6% | 0% |
| Rhinorrhea | 5% | 0% |
| Nausea | 5% | 2% |
| Pain in extremity | 4% | 0% |
| Asthenia | 4% | 0% |
- Hypersensitivity reactions
- Serious hypersensitivity reactions, including anaphylaxis, have occurred in patients receiving evinacumab. In trials, one patient (1%) experienced anaphylaxis during an evinacumab infusion. Monitor patients during infusions and treat reactions appropriately. Discontinue evinacumab if significant reactions occur.
- CONTRAINDICATIONS
- History of serious hypersensitivity reaction to evinacumab or any of its excipients
- PRECAUTIONS
- Kidney disease
- CrCl ≥ 30 ml/min: observed trough concentrations at steady-state were comparable between patients with mild or moderate renal impairment and patients with normal renal function
- CrCl < 30 ml/min: has not been studied. Manufacturer makes no recommendation.
- Liver disease
- Has not been studied. Manufacturer makes no recommendation.
- Pregnancy
- In animal studies, evinacumab was toxic to developing rabbit embryos at doses below those used in humans. Consider obtaining a pregnancy test prior to therapy. Women of reproductive potential should be advised to use contraception during evinacumab therapy and for at least 5 months following the last dose.
- DRUG INTERACTIONS
- NOTE: Drug interactions presented here are NOT all-inclusive. Other interactions may exist. The interactions presented here are meant to encompass commonly prescribed medications and/or interactions that are well-documented. Always consult your physician or pharmacist before taking medications concurrently. CLICK HERE for more information on drug interactions.
- Evinacumab
- Evinacumab has no known drug interactions
- Metabolism and clearance
- The metabolism of evinacumab has not been completely defined. It is likely degraded like other antibodies into small peptides and amino acids via catabolic pathways.
- DOSING
- Dosage forms
- 345 mg/2.3 ml (150 mg/ml) single dose vial
- 1200 mg/8 ml (150 mg/ml) single dose vial
- Store in refrigerator
- Dosing (HoFH ≥ 12 years old)
- 15 mg/kg administered by intravenous (IV) infusion over 60 minutes once monthly (every 4 weeks)
- If a dose of evinacumab is missed, administer as soon as possible. Thereafter, evinacumab should be scheduled monthly from the date of the last dose.
- The LDL-lowering effect of evinacumab may be measured as early as 2 weeks after initiation
- LONG-TERM SAFETY
- Evinacumab was FDA-approved in 2021. There is no long-term safety data available.
- BIBLIOGRAPHY
- 1 - Evkeeza PI