Epysqli

Epysqli (eculizumab-aagh) is used to treat paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), generalized myasthenia gravis (gMG) in adults who are anti-acetylcholine receptor (AChR) antibody positive, and neuromyelitis optica spectrum disorder (NMOSD) in adults who are anti-aquaporin-4 (AQP4) antibody positive. It is given by a healthcare provider as an intravenous (IV) infusion.

Epysqli works by targeting the complement system (a part of the immune system) to prevent it from destroying red blood cells or damaging blood vessels. It binds to complement protein C5, blocking its breakdown into C5a (a proinflammatory toxin) and C5b (which triggers the membrane attack complex, leading to cell rupture). In PNH, this prevents complement-mediated destruction of red blood cells. In aHUS, it prevents complement-mediated thrombotic microangiopathy (TMA).

Epysqli (eculizumab-aagh) received FDA approval on July 19, 2024, and is an interchangeable biosimilar to Soliris. Epysqli is manufactured by Samsung Bioepis Co., Ltd.

FDA approvals and uses

Epysqli (eculizumab-aagh) is FDA approved for:

• Paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis (adult dosing is the only PNH regimen provided in the label)
• Atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy (adults and pediatric approval) Not indicated for the treatment of patients with Shiga toxin E. coli-related hemolytic uremic syndrome (STEC-HUS).
• Generalized myasthenia gravis (gMG) in adults who are anti-acetylcholine receptor (AChR) antibody positive.
• Neuromyelitis optica spectrum disorder (NMOSD) in adults who are anti-aquaporin-4 (AQP4) antibody positive.

• Your healthcare provider will give you Epysqli into your vein through an intravenous (IV) line, usually over 35 minutes in adults and 1 to 4 hours in children.
• Adults will usually receive an Epysqli infusion weekly for 5 weeks, then every 2 weeks.
• For children less than 18 years of age, your healthcare provider will decide how often you receive Epysqli depending on age and body weight.
• After each infusion, you should be monitored for at least 1 hour for infusion-related reactions. See Epysqli side effects, above.
• If you have an infusion-related reaction during your infusion, your healthcare provider may decide to give Epysqli more slowly or stop your infusion.
• If you miss an Epysqli infusion, call your healthcare provider right away.

If you have PNH, your healthcare provider will need to monitor you closely for at least 8 weeks after stopping Epysqli. Stopping treatment may cause breakdown of your red blood cells due to PNH. Symptoms or problems that can happen due to red blood cell breakdown include a drop in your red blood cell count, kidney problems, a drop in your platelet count, blood clots, confusion, difficulty breathing, and chest pain.

If you have aHUS, your healthcare provider will need to monitor you closely for at least 12 weeks after stopping Epysqli for signs of worsening aHUS symptoms or problems related to abnormal clotting (thrombotic microangiopathy). Symptoms or problems that can happen with abnormal clotting may include stroke, difficulty breathing, confusion, kidney problems, seizures, swelling in the arms or legs, chest pain (angina), and a drop in your platelet count.

Epysqli (eculizumab-aagh) is a medicine that affects your immune system and carries a Boxed Warning for serious and life-threatening infections caused by Neisseria meningitidis bacteria. Epysqli can lower the ability of your immune system to fight infections.

• Epysqli increases your chance of getting serious meningococcal infections caused by Neisseria meningitidis bacteria. Meningococcal infections may quickly become life-threatening or cause death if not recognized and treated early. You must complete or update your meningococcal vaccines (for serogroups A, C, W, Y, and B) at least 2 weeks before your first dose of Epysqli. If you have not completed your meningococcal vaccines and Epysqli must be started right away, you should receive the required vaccine(s) as soon as possible. If you have not been vaccinated and Epysqli must be started right away, you should also receive antibiotics to take for as long as your healthcare provider tells you. If you had a meningococcal vaccine in the past, you might need additional vaccines before starting Epysqli. Your healthcare provider will decide if you need additional meningococcal vaccines. Meningococcal vaccines do not prevent all meningococcal infections. Call your healthcare provider or get emergency medical care right away if you get any of these signs and symptoms of a serious meningococcal infection:

• fever fever with high heart rate headache and fever confusion muscle aches with flu-like symptoms fever and a rash headache with nausea or vomiting headache with a stiff neck or stiff back eyes sensitive to light.

Your healthcare provider will give you a Patient Safety Card about the risk of serious meningococcal infection. Carry it with you at all times during treatment and for 3 months after your last dose of Epysqli. Your risk of meningococcal infection may continue for several weeks after your last dose of Epysqli. It is important to show this card to any healthcare provider who treats you, as this will help them diagnose and treat you quickly.

Epysqli REMS

Epysqli is only available through a program called the Epysqli Risk Evaluation and Mitigation Strategy (REMS). Before you can receive Epysqli, your healthcare provider must:

• enroll in the Epysqli REMS program
• counsel you about the risk of serious meningococcal infections
• give you information about the signs and symptoms of serious meningococcal infection
• make sure that you are vaccinated against serious infections caused by meningococcal bacteria, and that you receive antibiotics if you need to start Epysqli right away, and you are not up to date on your vaccines
• give you a Patient Safety Card about your risk of meningococcal infection, as discussed above

Risk of Other Serious Infections

Epysqli may also increase the risk of other types of serious infections caused by encapsulated bacteria, including Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria gonorrhoeae.

• If your child is treated with Epysqli, your child should receive vaccines against Streptococcus pneumoniae and Haemophilus influenzae type b (Hib).
• Certain people may be at risk of serious infections with gonorrhea. Talk to your healthcare provider about whether you are at risk for gonorrhea infection, about gonorrhea prevention, and regular testing.
• Certain fungal infections (aspergillus) may also happen if you take Epysqli and have a weak immune system or a low white blood cell count.

For more information about side effects, see below.

Do not receive Epysqli if you have a serious meningococcal infection when you are starting Epysqli treatment.

Before you receive Epysqli, tell your healthcare provider about all of your medical conditions, including if you:

• have an infection or fever
• have allergies to Epysqli, eculizumab, or Soliris
• are pregnant or plan to become pregnant. It is not known if Epysqli will harm your unborn baby
• are breastfeeding or plan to breastfeed. It is not known if Epysqli passes into your breast milk.

Epysqli pregnancy and breastfeeding warnings (more detail)

Serious side effects

Epysqli may also cause other serious side effects, such as:

• Serious infusion-related reactions. These can happen during your Epysqli infusion. Tell your healthcare provider or nurse right away if you get any of these symptoms during your Epysqli infusion: chest pain trouble breathing or shortness of breath swelling of your face, tongue, or throat feel faint or pass out
• If you have an infusion-related reaction to Epysqli, your healthcare provider may need to infuse Epysqli more slowly or stop Epysqli.

Common side effects

The most common side effects of Epysqli in people with PNH are:

• headache
• back pain
• nasopharyngitis (pain or swelling of the nose or throat)
• nausea.

The most common side effects of Epysqli in people with aHUS are:

• headache
• diarrhea
• high blood pressure (hypertension)
• common cold (upper respiratory infection)
• stomach-area (abdominal) pain
• vomiting
• pain or swelling of your nose or throat (nasopharyngitis)
• low red blood cell (anemia)
• cough
• swelling of legs or feet (peripheral edema)
• nausea
• urinary tract infections
• fever.

The most common side effects in people with gMG treated with Epysqli are:

• muscle and joint (musculoskeletal) pain.

The most common side effects in people with NMOSD treated with Epysqli are:

• common cold (upper respiratory infection)
• pain or swelling of your nose or throat (nasopharyngitis)
• diarrhea
• back pain
• dizziness
• flu (influenza)
• joint pain (arthralgia)
• throat irritation (pharyngitis)
• bruising (contusion).

Tell your healthcare provider about any side effect that bothers you or that does not go away. These are not all the possible side effects of Epysqli. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Epysqli side effects (more detail)

Dose of Epysqli for PNH (Adults 18+)

• Initial: 600 mg intravenously weekly for the first 4 weeks
• Week 5: 900 mg intravenously
• Week 7 onwards: 900 mg intravenously every 2 weeks thereafter.

Dose of Epysqli for aHUS

Adults (18+)

• Initial: 900 mg intravenously weekly for the first 4 weeks
• Week 5: 1,200 mg intravenously
• Week 7 onwards: 1,200 mg intravenously every 2 weeks thereafter.

Pediatric patients

• Administer Epysqli based on body weight. See the Epysqli Prescribing Information.

Dose of Epysqli for gMG (Adults 18+)

• Initial: 900 mg intravenously weekly for the first 4 weeks
• Week 5: 1,200 mg intravenously
• Week 7 onwards: 1,200 mg intravenously every 2 weeks thereafter.

Dose of Epysqli for NMOSD (Adults 18+)

• Initial: 900 mg intravenously weekly for the first 4 weeks
• Week 5: 1,200 mg intravenously
• Week 7 onwards: 1,200 mg intravenously every 2 weeks thereafter.

If you miss an Epysqli infusion, call your healthcare provider right away.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Epysqli and other medicines can affect each other, causing side effects.

• A supplemental dose of Epysqli is required for patients with aHUS, gMG, or NMOSD who are undergoing plasmapheresis or plasma exchange, or receiving a fresh frozen plasma infusion. Patients with gMG also require a supplemental dose when receiving intravenous immunoglobulin (IVIg).
• Monitor patients taking neonatal Fc receptor blockers (FcRn), such as efgartigimod or rozanolixizumab, closely for reduced effectiveness of Epysqli.

Know the medications you take and the vaccines you receive. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. See the Epysqli Package Insert for a full list of interactions.

Active ingredient: eculizumab-aagh.

Inactive ingredients: dibasic sodium phosphate, monobasic sodium phosphate, polysorbate 80 (vegetable origin), trehalose, and Water for Injection.

Supplied as one 300 mg/30 mL (10 mg/mL) single-dose vial per carton.

Epysqli is manufactured by Samsung Bioepis Co., 76, Songdogyoyuk-ro, Yeonsu-gu, Incheon 21987, Republic of Korea. US License Number 2046.

Biosimilar and interchangeable products are biological products that are highly similar to and have no clinically meaningful differences from the reference product.

Reference products

These are biological products that have already been approved by the FDA, against which biosimilar products are compared. There is 1 for Epysqli.

Soliris (eculizumab) - Alexion Pharmaceuticals, Inc.

View Soliris information in detail.

Soliris interchangeable products

Interchangeable biosimilar products can be dispensed by a pharmacist without the intervention of the prescriber of the reference product.

Pharmacy laws for biosimilar prescribing may vary by state.

Bkemv (eculizumab-aeeb) - Amgen Inc.

View Bkemv information in detail.

Epysqli (eculizumab-aagh) - Samsung Bioepis Co., Ltd.