Pegcetacoplan

Pegcetacoplan (brand name Empaveli) is a twice-weekly, injectable medicine that is used to treat adults with paroxysmal nocturnal hemoglobinuria (PNH) or to reduce proteinuria and the loss of kidney function in adults and children 12 years and older with C3 glomerulopathy (C3G) or primary immune-complex membranoproliferative glomerulonephritis (IC-MPGN). It is given by subcutaneous infusion using an infusion pump or the on-body Empaveli injector.

• An ophthalmic form of pegcetacoplan (brand name Syfovre) is used to treat an eye condition called geographic atrophy in adults with age-related macular degeneration.

Pegcetacoplan works by targeting the immune system, and its mechanism of action (MOA) in PNH is to block a specific protein (C3) involved in breaking down red blood cells. This helps prevent intravascular hemolysis (IVH, the destruction of red blood cells in the circulation) and extravascular hemolysis (EVH, the breakdown of red blood cells in the spleen, bone marrow, or liver by macrophages). Pegcetacoplan is the only treatment that targets C3 and may prevent both forms of red blood cell destruction (IVH and EVH). It works higher in the complement system than other treatments used for PNH.

In C3G and primary IC-MPGN, excessive complement activity causes harmful C3 fragment deposits in kidney filters, leading to damage. Pegcetacoplan targets C3 and C3b proteins, interrupting the complement pathway to prevent toxic accumulation and reduce renal inflammation and injury.

Because of the risk of infections, pegcetacoplan is only available under the brand name Empaveli and through a restricted program called the Empaveli REMS. Your healthcare provider must be a member of this program to be able to prescribe pegcetacoplan and provide you with the necessary information and a Patient Safety Card. Only pharmacies certified for the Empaveli REMS program can dispense Empaveli.

Pegcetacoplan gained FDA approval on May 14, 2021, under the brand, Empaveli, for PNH. Approval was extended on July 28, 2025, to include C3G and IC-MPGN. There is no Empaveli generic available. Intravitreal pegcetacoplan gained FDA approval on February 17, 2023, under the brand name Syfovre.

Apellis Pharmaceuticals makes pegcetacoplan for PNH, C3G and IC-MPGN.

Pegcetacoplan is given subcutaneously (this means under the skin) using an infusion pump or the Empaveli injector. Use this medicine exactly as your healthcare provider tells you. Do not infuse more or less than your healthcare provider tells you to.

• Your doctor or nurse will show you how to use the Injector or infusion pump so you can administer it at home, or a caregiver can administer it to you.
• It is usually given twice a week, although a healthcare provider may instruct some people to administer it every three days.

Your healthcare provider will give you an Empaveli Patient Safety Card about the risk of serious infections. Carry it with you at all times during treatment and for 2 months after your last dose. Your risk of serious infections may continue for several weeks after your last dose. It is important to show this card to any healthcare provider who treats you. This will help them diagnose and treat you quickly.

Do not take pegcetacoplan if you:

• are allergic to pegcetacoplan, Empaveli, or any of the other ingredients in the injection
• have not been fully vaccinated against Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type B, unless your healthcare provider decides that urgent treatment with pegcetacoplan is needed
• have an unresolved serious infection caused by encapsulated bacteria.

Before you take pegcetacoplan, tell your healthcare provider about all of your medical conditions, including if you:

• have an infection or fever
• have not had all your childhood vaccinations
• are pregnant, plan to become pregnant, or are breastfeeding.

Pregnancy and breastfeeding

Pegcetacoplan may harm your unborn baby. Females who can become pregnant should have a pregnancy test before starting treatment and use an effective method of birth control (contraception) during treatment, and for 40 days after the final dose.

Breastfeeding

It is not known if pegcetacoplan passes into breast milk. You should not breastfeed during treatment, and for 40 days after the final dose.

The most common side effects of pegcetacoplan for PNH include:

• injection-site reactions, such as redness, pain, or swelling at the injection site
• infections
• diarrhea
• pain in the stomach (abdomen)
• pain in the arms and legs
• low potassium levels
• tiredness
• cough
• joint pain
• dizziness
• headache
• a rash.

The most common side effects of pegcetacoplan for C3G or primary IC-MPGN are:

• infusion-site reactions
• fever
• nasopharyngitis (a cold)
• Influenza
• cough
• nausea.

Serious side effects and warnings

Pegcetacoplan can cause serious side effects, such as serious infections by encapsulated bacteria.

Pegcetacoplan can lower the ability of your immune system to fight infections and increase your risk of developing serious and life-threatening infections, including meningitis caused by encapsulated bacteria such as Streptococcus pneumoniae; Neisseria meningitidis, types A, C, W, Y, and B; and Haemophilus influenzae type B. You must be vaccinated against these bacteria at least 2 weeks before your first dose if you have not already had these vaccines. If your healthcare provider decides that urgent treatment with pegcetacoplan is needed, you should receive the required vaccinations as soon as possible, and you should also receive antibiotics to take for as long as your healthcare provider tells you. Meningococcal infections may quickly become life-threatening and cause death if not recognized and treated early. Call your healthcare provider or get emergency medical care right away if you get any of these signs and symptoms of a serious infection once you have started taking pegcetacoplan:

• fever with or without shivers or chills
• fever and a rash
• fever with breathlessness or fast breathing
• fever with chest pain and cough
• headache with nausea or vomiting
• fever with high heart rate
• headache and a fever
• headache with a stiff neck or stiff back
• confusion
• muscle aches with flu-like symptoms
• eyes sensitive to light
• clammy skin.

May cause infusion-related reactions or allergic reactions including anaphylaxis which may be life-threatening. Stop your infusion and seek immediate medical attention if you develop any of the following: chest pain; difficulty breathing, including shortness of breath and wheezing; swollen face, tongue or throat; feeling faint; rapid heart rate; skin reactions, including rash, hives and itching; nausea or vomiting; confusion and anxiety; dizziness or fainting. If any of these symptoms happen during an infusion, stop your infusion and tell your healthcare provider or get emergency medical care right away.

After stopping pegcetacoplan, patients with PNH will be closely monitored by their healthcare provider for at least 8 weeks for dangerous red blood cell breakdown (hemolysis). Warning signs include elevated LDH levels, fatigue, dark urine, stomach pain, breathing problems, blood clots, swallowing difficulties, or erectile dysfunction. If hemolysis occurs, consider restarting pegcetacoplan.

May interfere with laboratory tests, such as those that use silica reagents in coagulation panels (may cause an artificially prolonged activated partial thromboplastin time [aPTT]).

It is not known if pegcetacoplan is safe and effective in children.

Tell your healthcare provider about any side effect that bothers you or that does not go away. These are not all of the possible side effects. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088 or contact Apellis Pharmaceuticals, Inc. at 1-833-866-3346.

Dose of Pegcetacoplan for PNH for adults:

• Recommended dosage: 1080 mg (one injection vial) administered subcutaneously twice weekly.
• Pegcetacoplan can be administered via a commercially available infusion pump or with the Empaveli injector.

Dose of Pegcetacoplan for C3G or IC-MPGN

• Adults 18 and older: 1080 mg (one injection vial) administered subcutaneously twice weekly.
• Children 12 years to less than 18 years: Dosage is based on weight.

• Pegcetacoplan can be administered via a commercially available infusion pump or with the Empaveli injector.

Administration of pegcetacoplan via an infusion pump

It should be administered into a clear area of skin on your stomach (avoid around the belly button), or the top of your thighs, hips, or upper arms.

• If you are using the infusion pump, it usually takes around 30 minutes to infuse (if using two infusion sites) or approximately 60 minutes (if using one infusion site). See the product information for complete details about the administration process.

Administration of pegcetacoplan via the Empaveli injector

The Empaveli injector is a compact, single-use device that is attached to your body and delivers your dose of pegcetacoplan subcutaneously (under the skin) of your abdomen, allowing you greater mobility while the infusion is in process.

• A push button starts the injection, and the hidden needle automatically retracts upon dose completion.

If you miss a dose, take the missed dose as soon as possible. Take your next dose at your regularly scheduled time.

Do not stop taking pegcetacoplan without your doctor's advice. After stopping it, your healthcare provider will need to monitor you closely for at least 8 weeks, because stopping treatment may cause a breakdown of red blood cells due to PNH, and symptoms such as:

• decreased hemoglobin level in your blood
• blood in your urine
• shortness of breath
• trouble swallowing
• tiredness
• pain in the stomach (abdomen)
• blood clots
• erectile dysfunction (ED).

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Sometimes it is not safe to use certain medications at the same time as pegcetacoplan. Some drugs can affect your blood levels of other drugs you take, which may increase side effects or make the medications less effective. Tell your doctor about all your vaccinations and your medicines, including prescription, over-the-counter, vitamins, and herbal supplements.

Store pegcetacoplan vials in the refrigerator between 36°F to 46°F (2°C to 8°C) in the original carton to protect from light.

Do not use past the expiration date stamped on the carton.

Keep all medicines out of the reach of children and pets.

Pegcetacoplan is only available as the brand Empaveli.

Empaveli ingredients

Active ingredient: pegcetacoplan

Inactive ingredients: sorbitol, glacial acetic acid, sodium acetate trihydrate, Water for Injection USP. Pegcetacoplan may also contain sodium hydroxide and/or additional glacial acetic acid for pH adjustment.

Empaveli is available as a subcutaneous injection containing 1080 mg/20mL (54 mg/mL) in a single-dose vial.

Pegcetacoplan for infusion is manufactured by Apellis Pharmaceuticals, under the brand name Empaveli. Their headquarters are in Waltham, Massachusetts. Other notable medications by Apellis include:

• Syfovre (pegcetacoplan intravitreal injection) for the treatment of geographic atrophy (GA), an advanced form of dry age-related macular degeneration (AMD) that causes vision loss.