Evkeeza (Evinacumab)
Monoclonal antibody for treating homozygous familial hypercholesterolemia (HoFH)
Quick facts about Evkeeza
The most important things you need to know
- Unique mechanism of action: Evkeeza targets ANGPTL3, working independently of LDL receptors – effective even when statins and PCSK9 inhibitors fail
- For a rare, severe condition: Approved specifically for homozygous familial hypercholesterolemia (HoFH), affecting approximately 1 in 250,000–300,000 people worldwide
- Monthly IV infusion: Given as a 60-minute intravenous infusion once monthly at a dose of 15 mg/kg body weight, administered by a healthcare professional
- Pregnancy warning: May harm the unborn child – effective contraception required during treatment and for 5 months after the last dose
- Watch for allergic reactions: Serious hypersensitivity reactions including anaphylaxis can occur – the infusion will be stopped immediately if signs appear
What Is Evkeeza and What Is It Used For?
Evkeeza contains the active substance evinacumab, which belongs to a class of medicines known as monoclonal antibodies. Monoclonal antibodies are proteins specifically designed to attach to and block certain target substances in the body. In the case of evinacumab, the target is a protein called angiopoietin-like protein 3, commonly referred to as ANGPTL3.
Evkeeza is approved for the treatment of adults and children aged 6 months and older with homozygous familial hypercholesterolemia (HoFH). This is a rare genetic condition in which a person inherits defective copies of the genes responsible for LDL receptor function from both parents. As a result, patients with HoFH have extremely high levels of LDL cholesterol (“bad cholesterol”) from birth, often exceeding 500 mg/dL (13 mmol/L) without treatment. These dangerously elevated levels lead to premature atherosclerotic cardiovascular disease, including heart attacks, aortic valve disease, and other serious complications, often before the age of 30.
Evkeeza is always used alongside a low-fat diet and other lipid-lowering medications such as statins, ezetimibe, or PCSK9 inhibitors. It is not a replacement for existing therapy but rather an add-on treatment for patients who do not achieve adequate cholesterol reduction with conventional approaches alone. The European Medicines Agency (EMA) granted conditional marketing authorization for Evkeeza in 2021, recognizing the critical unmet medical need in the HoFH population.
How Does Evkeeza Work?
The mechanism of action of evinacumab is fundamentally different from that of statins and PCSK9 inhibitors. While these conventional cholesterol-lowering drugs rely on upregulating or preserving LDL receptor function to clear LDL cholesterol from the bloodstream, evinacumab operates through an entirely LDL receptor-independent pathway. This distinction is crucial for patients with HoFH who may have no functional LDL receptors at all.
ANGPTL3 is a protein produced primarily by the liver that normally inhibits two key enzymes: lipoprotein lipase (LPL) and endothelial lipase (EL). By blocking ANGPTL3, evinacumab releases these enzymes from inhibition, leading to enhanced clearance of triglyceride-rich lipoproteins and increased catabolism of very low-density lipoprotein (VLDL). This, in turn, reduces the substrate available for LDL production, resulting in significant reductions in LDL cholesterol, triglycerides, and total cholesterol levels.
In clinical trials, evinacumab demonstrated mean LDL cholesterol reductions of approximately 47–49% compared to placebo in patients with HoFH, including those with null/null LDL receptor mutations who derive minimal benefit from statins or PCSK9 inhibitors. This makes Evkeeza a breakthrough treatment for patients who had previously exhausted all available therapeutic options.
What Should You Know Before Taking Evkeeza?
Contraindications
Evkeeza must not be administered to patients who are allergic (hypersensitive) to evinacumab or to any of the other ingredients in the formulation. These excipients include proline, arginine hydrochloride, histidine hydrochloride monohydrate, polysorbat 80, histidine, and water for injections. If you have ever had a reaction to any monoclonal antibody therapy, discuss this with your healthcare provider before starting Evkeeza.
Warnings and Precautions
Before starting treatment with Evkeeza, it is essential to discuss your complete medical history with your doctor or nurse. Evkeeza can cause serious allergic (hypersensitivity) reactions, including anaphylaxis, which is a potentially life-threatening condition requiring immediate medical intervention.
- Swelling of the lips, tongue, or throat making it difficult to swallow or breathe
- Difficulty breathing or wheezing
- Dizziness or fainting
- Skin rash or hives (urticaria)
- Itching
If such a reaction occurs, the infusion will be stopped immediately, and you may need additional medications to manage the allergic response. Your healthcare team will monitor you during and after each infusion for signs of hypersensitivity.
Evkeeza is not recommended for children under 6 months of age due to insufficient data on safety and efficacy in this very young population. For older children and adults, the safety profile has been characterized in clinical trials, though ongoing post-marketing surveillance continues to evaluate long-term outcomes.
Evkeeza contains proline (30 mg per mL), which may be harmful to patients with hyperprolinemia, a rare inherited disorder causing accumulation of proline in the body. Do not use this medicine if you or your child has hyperprolinemia unless specifically recommended by your doctor.
This medicine also contains polysorbate 80 (1 mg per mL), which can cause allergic reactions. Inform your doctor if you have any known allergies to polysorbates.
Pregnancy and Breastfeeding
Evkeeza may cause harm to the developing fetus and should not be used during pregnancy. If you are pregnant, suspect you might be pregnant, or are planning to become pregnant, consult your doctor before receiving this medication. If you become pregnant while being treated with Evkeeza, inform your doctor immediately so that appropriate steps can be taken.
Women of childbearing potential must use effective contraception throughout the duration of Evkeeza treatment and for at least 5 months after the final dose. This extended period is necessary because monoclonal antibodies can remain in the body for several months after the last administration. Your doctor can advise you on the most suitable contraceptive method during this time.
It is currently unknown whether evinacumab passes into breast milk. Because many monoclonal antibodies are excreted in human milk, the potential risk to the breastfed infant cannot be excluded. If you are breastfeeding or planning to breastfeed, seek medical advice before receiving Evkeeza. Your doctor will help you weigh the benefits of breastfeeding against the potential risks.
Driving and Operating Machinery
Evkeeza may cause dizziness and fatigue, which could impair your ability to drive, cycle, or operate machinery. If you feel affected after receiving an infusion, refrain from these activities and inform your healthcare provider.
How Does Evkeeza Interact with Other Drugs?
As a monoclonal antibody, evinacumab is not metabolized through the cytochrome P450 enzyme system, which is the primary pathway for drug-drug interactions with most small-molecule medications. Therefore, pharmacokinetic interactions with commonly used drugs such as statins, ezetimibe, or PCSK9 inhibitors are not expected. In clinical practice, Evkeeza is typically administered in combination with these lipid-lowering therapies.
However, it is critically important to inform your healthcare provider about all medications you are currently taking, have recently taken, or might take in the future. This includes prescription medicines, over-the-counter medications, vitamins, and herbal supplements. Although direct pharmacokinetic interactions are unlikely, your doctor needs a complete picture of your treatment regimen to provide the safest and most effective care.
Patients with HoFH often receive multiple lipid-lowering agents simultaneously. Evkeeza has been studied alongside statins (such as atorvastatin and rosuvastatin), ezetimibe, PCSK9 inhibitors (such as evolocumab and alirocumab), and LDL apheresis. In these studies, no clinically significant interactions were observed. The combination approach is intentional, as each agent targets a different aspect of lipid metabolism, and additive effects on LDL cholesterol reduction are expected.
| Medication Class | Examples | Interaction Risk | Notes |
|---|---|---|---|
| Statins | Atorvastatin, Rosuvastatin | Low | Often used together; different mechanism of action |
| Ezetimibe | Ezetimibe (Zetia) | Low | Inhibits cholesterol absorption; complementary effect |
| PCSK9 Inhibitors | Evolocumab, Alirocumab | Low | Different target; may be used together in HoFH |
| Lomitapide | Lomitapide (Juxtapid) | Low | MTP inhibitor; may be combined under specialist supervision |
| Bile Acid Sequestrants | Colesevelam, Cholestyramine | Low | No expected interaction with IV-administered antibodies |
What Is the Correct Dosage of Evkeeza?
Evkeeza is administered exclusively in a clinical setting by a healthcare professional. It is given as an intravenous (IV) infusion, meaning the medicine is slowly dripped into a vein through an IV line over a period of 60 minutes. The drug is not available as an oral medication or as a self-administered injection.
Adults
Standard Adult Dosage
The recommended dose is 15 mg per kilogram (mg/kg) of body weight, administered as an intravenous infusion over 60 minutes approximately once every 4 weeks. For example, a patient weighing 70 kg would receive a dose of 1,050 mg per infusion.
Children (6 months and older)
Pediatric Dosage
The same weight-based dose of 15 mg/kg body weight applies to children aged 6 months and older. The infusion volume and rate are adjusted based on the child’s weight:
- Children weighing 3–25 kg: Maximum infusion volume of 5 mL/kg, administered at a rate not exceeding 5 mL/kg/hour
- Children weighing 26–44 kg: Maximum infusion volume of 150 mL
- Patients weighing 45 kg or more: Maximum infusion volume of 250 mL
Evkeeza is not recommended for infants under 6 months of age due to insufficient safety and efficacy data.
Elderly
No dose adjustment is required for elderly patients. The same weight-based dosing regimen of 15 mg/kg applies regardless of age. Clinical trial data included patients across a range of ages, and no clinically significant differences in safety or efficacy were observed in older patients.
Missed Dose
If you miss an appointment for your Evkeeza infusion, contact your doctor or nurse as soon as possible to reschedule. It is important to maintain the regular monthly dosing schedule to achieve optimal cholesterol reduction. Do not attempt to double the dose to make up for a missed infusion.
Overdose
Because Evkeeza is administered by healthcare professionals in a controlled clinical setting, the risk of overdose is minimal. In clinical studies, doses up to 20 mg/kg have been administered without unexpected safety signals. If an overdose is suspected, the patient should be monitored for signs of adverse effects, and standard supportive measures should be employed as needed. There is no specific antidote for evinacumab.
| Body Weight | Dose (15 mg/kg) | Max Infusion Volume | Infusion Duration |
|---|---|---|---|
| 3–25 kg | 45–375 mg | 5 mL/kg (15–125 mL) | 60 minutes |
| 26–44 kg | 390–660 mg | 150 mL | 60 minutes |
| 45–70 kg | 675–1,050 mg | 250 mL | 60 minutes |
| 71–100 kg | 1,065–1,500 mg | 250 mL | 60 minutes |
| >100 kg | >1,500 mg | 250 mL | 60 minutes |
What Are the Side Effects of Evkeeza?
Like all medicines, Evkeeza can cause side effects, although not everyone who receives the treatment will experience them. Most side effects are mild to moderate in severity and tend to resolve on their own without requiring treatment discontinuation. However, certain adverse reactions, particularly severe allergic reactions, require immediate medical attention.
The safety profile of evinacumab has been established through clinical trials in both adult and pediatric patients with HoFH. The most frequently reported side effects are listed below, categorized by how commonly they occur. Understanding these frequency categories helps patients and caregivers set appropriate expectations and recognize when medical attention may be needed.
Very Common
- Nasopharyngitis (cold-like symptoms with runny nose)
- Fatigue (in children aged 5–11 years)
Common
- Dizziness
- Upper respiratory tract infection (sore throat or sinus infection)
- Nausea
- Abdominal pain (stomach pain)
- Constipation
- Back pain
- Pain in extremities (hands or feet)
- Influenza-like symptoms
- Asthenia (feeling tired or weak)
- Infusion-related reactions (such as itching at the infusion site)
Uncommon – Serious
- Severe allergic reactions (anaphylaxis) – including swelling of lips, tongue, or throat; difficulty breathing or wheezing; dizziness or fainting; skin rash or hives; itching
If you experience any signs of a severe allergic reaction during or after your infusion, such as difficulty breathing, swelling of the face or throat, severe dizziness, or widespread rash, tell your healthcare team immediately. The infusion will be stopped at once and emergency treatment will be provided. Do not wait to see if symptoms improve on their own.
Infusion-related reactions are generally mild and may include symptoms such as itching at the IV site, mild flushing, or a slight feeling of warmth. If these symptoms become bothersome, the infusion rate may be slowed, temporarily paused, or stopped entirely at the discretion of your healthcare provider.
If you experience any side effects not listed here, or if existing side effects become more severe, inform your doctor or nurse. Reporting adverse reactions helps regulatory authorities monitor the ongoing safety of medicines. You can report side effects directly to your national medicines regulatory agency.
How Should You Store Evkeeza?
Because Evkeeza is typically stored and prepared by healthcare professionals in clinical facilities, patients do not usually need to handle storage themselves. However, understanding the storage requirements can be helpful for awareness and safety purposes.
- Temperature: Store in a refrigerator at 2°C to 8°C (36°F to 46°F)
- Do not freeze. If accidentally frozen, do not use the product.
- Do not shake the vials, as this may damage the protein structure of the monoclonal antibody.
- Light protection: Keep in the original carton to protect from light until ready for use.
- Visual inspection: Before use, the solution should be clear to slightly opalescent, colorless to pale yellow. Do not use if it appears cloudy, discolored, or contains visible particles.
After the concentrated solution is diluted for infusion (in 0.9% sodium chloride or 5% dextrose), it should ideally be administered immediately. If immediate administration is not possible, the diluted solution may be stored temporarily:
- Refrigerated at 2–8°C for up to 24 hours (from preparation to completion of infusion)
- At room temperature (up to 25°C) for up to 6 hours (from preparation to completion of infusion)
Evkeeza vials are for single use only. Any unused solution remaining in the vial or in the infusion bag after treatment must be discarded in accordance with local regulations for the disposal of pharmaceutical waste. Do not save leftover solution for later use.
Always check the expiration date printed on the carton and vial label before use. The expiration date refers to the last day of that month. Do not use Evkeeza after its expiration date. Keep all medicines out of the sight and reach of children.
What Does Evkeeza Contain?
Evkeeza is supplied as a concentrate for solution for infusion. The formulation is designed to maintain the stability and biological activity of the evinacumab monoclonal antibody during storage and administration.
Active Substance
Each 1 mL of concentrate contains 150 mg of evinacumab. Evinacumab is a fully human monoclonal antibody produced by recombinant DNA technology in Chinese hamster ovary (CHO) cells. It targets and inhibits angiopoietin-like protein 3 (ANGPTL3).
Available Vial Sizes
- 2.3 mL vial: Contains 345 mg of evinacumab
- 8 mL vial: Contains 1,200 mg of evinacumab
Inactive Ingredients (Excipients)
The other ingredients that make up the Evkeeza formulation include:
- Proline – An amino acid that serves as a stabilizer to maintain protein structure
- Arginine hydrochloride – A buffering agent that helps maintain the correct pH
- Histidine hydrochloride monohydrate – Part of the buffer system for pH stability
- Histidine – An amino acid used as part of the buffering system
- Polysorbate 80 – A surfactant that prevents protein aggregation
- Water for injections – The solvent for the formulation
The solution appears clear to slightly opalescent, and colorless to pale yellow when visually inspected. Each vial is made of glass and designed for single use. The packaging includes one glass vial per carton, available in either the 2.3 mL or 8 mL size.
Frequently Asked Questions About Evkeeza
Medical References
All information is based on regulatory documents, international guidelines, and peer-reviewed research:
- European Medicines Agency (EMA) (2024). “Evkeeza (evinacumab) – Summary of Product Characteristics.” Official EMA product information. Last updated December 2024.
- U.S. Food and Drug Administration (FDA) (2021). “EVKEEZA (evinacumab-dgnb) Prescribing Information.” FDA-approved prescribing information for Evkeeza in the United States.
- Raal FJ, et al. (2020). “Evinacumab for Homozygous Familial Hypercholesterolemia.” New England Journal of Medicine. 383(8):711–720. ELIPSE HoFH pivotal trial demonstrating efficacy of evinacumab. Evidence level: 1A.
- Mach F, et al. (2020). “2019 ESC/EAS Guidelines for the Management of Dyslipidaemias.” European Heart Journal. 41(1):111–188. European Society of Cardiology guidelines for lipid management including HoFH.
- Cuchel M, et al. (2023). “2023 Update on European Atherosclerosis Society Consensus Statement on Homozygous Familial Hypercholesterolaemia.” European Heart Journal. 44(25):2277–2291. Updated EAS consensus on HoFH management including novel therapies.
- Rosenson RS, et al. (2022). “Evinacumab in Patients with Refractory Hypercholesterolemia.” Journal of the American College of Cardiology. 80(11):1046–1057. Clinical outcomes data for evinacumab in refractory hypercholesterolemia.
Evidence grading: This article uses the GRADE framework (Grading of Recommendations Assessment, Development and Evaluation) for evidence-based medicine. Clinical trial data referenced in this article represent Level 1A evidence from randomized controlled trials published in peer-reviewed journals.
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