InfoCons Consumer Protection informs you – ASPAVELI – Package Leaflet

Before anything else

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, or pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, or pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

ℹ️ 1. What ASPAVELI is and what it is used for

What is ASPAVELI ASPAVELI is a medicine that contains the active substance pegcetacoplan. Pegcetacoplan has been designed to attach to the C3 complement protein, which is a part of the body’s defence system called the ‘complement system’.

What is ASPAVELI used for Paroxysmal nocturnal haemoglobinuria (PNH) ASPAVELI is used to treat adult patients with a disease called paroxysmal nocturnal haemoglobinuria (PNH) who have anaemia as a result of this disease.

In patients with PNH, the ‘complement system’ is overactive and attacks their red blood cells, which can lead to low blood counts (anaemia), tiredness, difficulty in functioning, pain, abdominal pain, dark urine, shortness of breath, difficulty swallowing, erectile dysfunction, and blood clots. By attaching to and blocking the C3 protein, this medicine can stop the complement system from attacking red blood cells and so control symptoms of the disease. This medicine has been shown to increase the number of red blood cells (reduce anaemia), which may improve these symptoms.

C3 glomerulopathy (C3G) and primary immune -complex membranoproliferative glomerulonephritis (IC-MPGN) ASPAVELI is used to treat adult and adolescent patients (aged 12 to 17 years) with disease s called complement C3 glomerulopathy (C3G) or primary immune -complex membranoproliferative glomerulonephritis ( primary IC -MPGN) . For these diseases, ASPAVELI is used together with a renin – angiotensin -system inhibitor (RAS inhibitor), unless the use of a RAS inhibitor is not considered appropriate.

39 Glomerulone phritis is a kidney problem where there is inflammation in the kidney. C3G and primary IC-MPGN are types of glomerulonephritis. In patients with C3G or primary IC -MPGN, the ‘complement system’ is overactive and when this system is not well controlled, this can result in damage to the glomerulus, a network of small blood vessels in the kidney, which filters the blood.

Over time, this stops the kidneys from removing waste in the blood. This waste, if not removed from the blood, builds up in the body and may lead to kidney inflammation, damage and failure. This can lead to blood in the urine ( haematuria), excess protein in the urine (proteinuria), reduced kidney function (as measured by the glomerular filtration rate [GFR]) , high blood creatinine levels, tiredness and swelling (oedema) of hands, feet or ankles. This medicine has been shown to reduce the amount of protein in the urine and can stabilise kidney function.

⚠️ 2. What you need to know before you use ASPAVELI

Do not use ASPAVELI

• if you are allergic to pegcetacoplan or any of the other ingredients of this medicine (listed in section 6).
• if you have an infection caused by so -called encapsulated bacteria .
• if you are not vac cinated against Neisseria meningitidis , Streptococcus pneumoniae , and Haemophilus influenzae .

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using ASPAVELI .

Symptoms of infection Before starting ASPAVELI , inform your doctor if you have any infections.

Because the medicine targets the complement system, which is part of the body’s defences against infection, the use of this medicine increases your risk of infections, including those caused by the so-called encapsulated bacteria, such as Streptococcus pneumoniae , Neisseria meningitidis , and Haemophilus influenzae . These are severe infections affecting your nose, throat and lungs or the linings of the brain and can spread throughout the blood and body.

Talk to your doctor before you start ASPAVELI to be sure that you receive vaccination against Streptococcus pneumoniae , Neisseria meningitidis , and Haemophilus influenzae if you have not had these vaccines in the past . If you have had these vaccines in the past, you might still need additional vaccinations before starting this medicine . These vaccinations should be given at least 2 weeks before beginning therapy. If you cannot be vaccinated 2 weeks beforehand, your doctor will prescribe antibiotics to reduc e the risk of infection for 2 weeks after you have been vaccinated. Following vaccination, you may be more closely monitored by your doctor for symptoms of infection. Infection symptoms If you experience any of the following symptoms, you should immediately inform your doctor: – headache and a fever

• fever and a rash
• fever with or without shivers or chills
• shortness of breath
• high heart rate
• clammy skin
• headache with a stiff neck or stiff back
• headache with nausea (feeling sick) or vomiting
• eyes sensitive to light
• muscle aches with flu -like symptoms
• confusion
• extreme pain or discomfort 40 Make sure that you keep your vaccinations up to date. You should also be aware that vaccines reduce the risk of serious infections, but do not prevent all serious infections. In accordance with national recommendations, your doctor might consider that you need supplementary measures such as antibacterial medicines to prevent infection.

Allergic reactions Allergic reactions may appear in some patients. In case of severe allergic reaction, discontinue ASPAVELI infusion and seek medical help immediately. Severe allergic reaction may present as difficulty breathing, chest pain or chest tightness, and/or feeling dizzy/faint, severe itching of the skin or raised lumps on the skin, swelling of the face, lips, tongue and /or throat, which may cause difficulty in swallowing or collapse.

Injection site reactions Injection site reactions have been observed with the use of ASPAVELI. You should undergo appropriate training in proper injection technique before self- administering.

Laboratory monitoring for PNH During your treatment with ASPAVELI your doctor will perform regular check- ups, including blood tests for lactate dehydrogenase (LDH ) levels and tests of renal function, and may adjust your dose if needed.

Effects on laboratory tests Use of silica reagents in coagulation tests should be avoided as it can result in artificially prolonged activated partial thromboplastin time (aPTT).

Children and adolescents

Do not give this medicine to children with PNH under 18 years of age because it has not been studied in this age group.

Do not give this medicine to children with C3G or primary IC-MPGN under 12 years of age because it has not been studied in this age group.

Other medicines and ASPAVELI

Tell your doctor or pharmacist if you are using or have recently used or might use any other medicines.

Pregnancy, breast -feeding, and fertility Women of childbearing potential The effects of the medicine on an unborn child are not known. The use of effective contraception methods is recommended during treatment and up to 8 weeks after treatment by women who are able to get pregnant. Ask your doctor for advice before taking this medicine.

Pregnancy/breast- feeding ASPAVELI is not recommended during pregnancy and breast -feeding . If you are pregnant or breast -feeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before taking this medicine.

Driving and using machines

This medicine has no or negligible influence on the ability to drive and use machines.

ASPAVELI contains sorbitol

Sorbitol is a source of fructose. If your doctor has told you that you have an intolerance to some sugars or if you have been diagnosed with hereditary fructose intolerance (HFI), a rare genetic disorder in which a person cannot break down fructose, talk to your doctor before you take or receive this medicine.

41 ASPAVELI contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium -free’.

💊 3. How to use ASPAVELI

Always use this medicine exactly as your doctor has told you. Check with your doctor if you are not sure.

At least 2 weeks before you start treatment with this medicine, your doctor will review your medical records and may give you one or more vaccinations. If you cannot be vaccinated at least 2 weeks before you start treatment with ASPAVELI , to reduce the risk of infection, your doctor will prescribe antibiotics for 2 weeks after you have been vaccinated.

If you use this medicine to treat PNH Dose for adults :

The initial recommended dose for adults with PNH is 1 080 mg twice a week. You should take the twice weekly dose on Day 1 and Day 4 of each treatment week.

If you are switching to ASPAVELI from another type of PNH medicine, called a C5 inhibitor, you should take ASPAVELI in addition to your current dose of C5 inhibitor as prescribed for 4 weeks.

After 4 weeks you should stop taking your C5 inhibitor.

The dose or dosing interval should not be changed without consulting your doctor. Your doctor may adjust your dose to 1 080 mg every third day (e.g., Day 1, Day 4, Day 7, Day 10, Day 13, and so forth) if appropriate. If you think you have missed a dose, speak to your doctor as soon as possible.

If you use this medicine to treat C3G or primary IC -MPGN Dose for adults :

The initial recommended dose for adults with C3G or primary IC -MPGN is 1 080 mg twice a week.

You should take the twice weekly dose on Day 1 and Day 4 of each treatment week.

Dose for adolescents: The initial recommended twice a week dose for adolescents with C3G or primary IC -MPGN is based on the patient´s body weight. Your doctor will calculate your dose based on the below dosing table. You should take the twice weekly dose on Day 1 and Day 4 of each treatment week.

Body weight First dose (infusion volume) Second dose (infusion volume) Maintenance dose (infusion volume) 50 kg and above 1 080 mg twice weekly (20 mL) 35 to less than 50 kg 648 mg (12 mL) 810 mg (15 mL) 810 mg twice weekly (15 mL) 30 to less than 35 kg 540 mg (10 mL) 540 mg (10 mL) 648 mg twice weekly (12 mL) Method and route of administration ASPAVELI is intended to be given as an infusion under the skin using:

• an infusion pump or
• an on-body delivery system.

Your first doses of the medicine will be given to you by healthcare professionals in a clinic or treatment centre. If treatment goes well, your doctor may discuss with you the possibility of you giving the medicine yourself at home. If this is appropriate, a healthcare professional will train you or a caregiver how to give the infusion.

42 Infusion rate(s) Using the infusion pump, the infusion time is approximately 30 minutes if you use 2 infusion sites or approximately 60 minutes if using 1 site.

Using the on-body delivery system, the infusion time typically ranges from 30 to 60 minutes (depending on how quickly the medicine flows into your body).

The infusion should be started promptly after drawing this medicinal product into the syringe and completed within 2 hours after preparing the syringe .

43 Instructions for use – preparing the syringe Step 1 Prepare for infusion Before you start:

1. Remove a single vial carton from the refrigerator. Keep the vial in the carton at room temperature and allow it to warm up for approximately 30 minutes. Do not try to speed up the warming process using a microwave or any other heat source.

2. Find a well- lit, flat work surface area, like a table.

3. Gather your supplies: i) When using an infusion pump (Figure 1):

A. Syringe system infusion pump and manufacturer’s instructions (not shown) B. Compatible syringe C1. Transfer needle OR C2. Needleless transfer device to draw up product from the vial D. Infusion set (not shown; varies according to device manufacturer’s instructions) E. Infusion tubing and Y connector (if required) F. Sharps container G. Alcohol wipes H. Gauze and tape, or transparent dressing OR ii) When using an on -body delivery system (Figure 2):

A. On-body delivery system and manufacturer´s instructions (not shown) B. Compatible syringe C1. Transfer needle OR C2. Needleless transfer device to draw up product from the vial F. Sharps container G. Alcohol wipes Figure 1 Example of Supplies (infusion pump) Figure 2 Example of Supplies (on-body delivery system) Thoroughly clean your work surface using an alcohol wipe.

Wash your hands thoroughly with soap and water. Dry your hands.

44 Step 2 Check the vial and liquid Remove the vial from the carton.

Carefully look at the liquid in the vial.

ASPAVELI is a clear, colourless to slightly yellowish liquid. Check for particles or colour changes (Figure 3).

Do not use the vial if

• The liquid looks cloudy, contains particles, or is dark yellow.
• The protective flip cap is missing or damaged.
• The expiry date (EXP) on the label has passed. Figure 3 45 Step 3 Prepare and fill syringe Remove the protective flip cap from the vial to expose the central portion of the grey rubber stopper of the vial (Figure 4). Throw the cap away.

Clean the stopper with a new alcohol wipe and allow the stopper to dry.

Option 1: If using a needleless transfer device (such as a vial adapter), follow the instructions provided by the device manufacturer.

OR Option 2: If using a transfer needle and a syringe, follow the instructions below:

A. Attach a sterile transfer needle to a sterile syringe.

B. Pull back the plunger to fill the syringe with air, which should be about 20 mL (Figure 5).

C. Make sure the vial is in upright position. Do NOT turn the vial upside down. Push the air- filled syringe with the transfer needle attached through the centre of the vial stopper.

D. The tip of the transfer needle should not be in the solution to avoid creating bubbles. (Figure 6).

E. Gently push the air from the syringe into the vial. This will inject the air from the syringe into the vial.

F. Turn the vial upside down (Figure 7).

G. With the transfer needle tip in the solution slowly pull the plunger to fill the syringe with the prescribed dose of ASPAVELI (Figure 8 ).

H. Double check that you have withdrawn your prescribed dose.

Any excess volume should be disposed.

I. Remove the filled syringe and the transfer needle from the vial.

J. Do not recap the transfer needle. Unscrew the needle and throw it away in the sharps container. Figure 4 Figure 5 Figure 6 Figure 7 46 Figure 8 For infusion of the product using an on -body delivery system , follow the device manufacturer’s instructions. Throw away all used disposable supplies as well as any unused product and the empty vial as recommended by your healthcare professional.

For infusion of the product using a syringe system infusion pump, follow the steps below.

Step 4 Prepare syringe system infusion pump and tubing Gather the infusion pump supplies and follow the device manufacturer’s instructions to prepare the pump and tubing.

Step 5 Prepare the infusion site(s) A. Select an area on your abdomen (except for the five centimetres area around the belly button) , thighs, hips, or upper arms region for the infusion(s) (Figure 9).

B. Use a different site(s) from the one you used for your last infusion . If there are multiple infusion sites, they should be at least 7.5 cm apart. Rotate infusion sites in between each infusion (Figure 10 ).

C. Avoid the following infusion areas: a. Do not infuse into areas where the skin is tender, bruised, red, or hard. b. Avoid tattoos, scars, or stretch marks.

Figure 9 Figure 10 D. Clean the skin at each infusion site(s) with a new alcohol wipe, starting at the centre and working outward in a circular motion (Figure 11).

E. Let the skin dry. Figure 11 Step 6 Insert and secure the infusion needle(s) A. Pinch the skin between your thumb and forefinger around the infusion site (where you intend to place the needle). Insert the needle into the skin (Figure 12).

Follow the device manufacturer’s instructions on the angle of the needle.

B. Secure the needle(s) using sterile gauze and tape or a transparent dressing placed over the infusion site(s) (Figure 13).

Figure 12 Figure 13 Step 7 Start infusion Follow the device manufacturer’s instructions to start the infusion.

Start the infusion promptly after drawing the solution into the syringe.

Step 8 Complete infusion Follow the device manufacturer’s instructions to complete the infusion.

Step 9 Record infusion Record your treatment as directed by your healthcare professional.

48 Step 10 Clean up A. After the infusion is complete, remove the dressing and slowly take out the needle(s). Cover the infusion site with a new dressing.

B. Disconnect the infusion set from the pump and discard into the sharps container (Figure 14 ).

C. Throw away all used disposable supplies as well as any unused product and the empty vial as recommended by your healthcare professional.

D. Clean and store the syringe system infusion pump according to the device manufacturer’s instructions.

Figure 14

If you forget to use ASPAVELI

If you miss a dose, it should be taken as soon as possible; then take the next dose at the regularly planned time.

If you stop using ASPAVELI for treatment of PNH

PNH is a lifelong condition and so it is expected that you will use this medicine for a long time. If you wish to stop using the medicine, please speak to your doctor first. If you stop taking the medicine suddenly, you may be at risk of making your sympto ms worse.

If your doctor decides to stop your treatment with this medicine , follow their instructions for how to stop. Your doctor will monitor you closely for at least 8 weeks after stopping treatment for any signs of the destruction of red blood cells (haemolysis) due to PNH. Symptoms or problems that can happen due to destruction of red blood cell include:

• tiredness
• shortness of breath
• blood in the urine
• stomach -area (abdomen) pain
• drop in the number of your red blood cell count
• blood clots (thrombosis)
• trouble swallowing
• erectile dysfunction in males If you have any of these signs and symptoms, contact your doctor.

If you stop using ASPAVELI for treatment of C3G or primary IC -MPGN

C3G and primary IC -MPGN are lifelong conditions and so it is expected that you will use this medicine for a long time. If you wish to stop using the medicine, please speak to your doctor first.

❗ 4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Your doctor will discuss the possible side effects with you and explain the risks and benefits of ASPAVELI with you before treatment.

49 Serious side effects The most serious side effect is serious infection.

If you experience any of the infection symptoms (see section 2 “Infection symptoms ”), you should immediately inform your doctor.

Other side effects

If you are not sure what the side effects below are, ask your doctor to explain them to you.

Side effects reported in patients with PNH are listed below :

Very common (may affect more than 1 in 10 people)

• Reactions at the site of infusion: These include redness, swelling, itching, bruising and pain, or hardening of the skin. These reactions usually go away within a few days.
• Infection of the nose, throat, or airways (upper respiratory tract infection)
• Diarrhoea
• Destruction of red blood cells (haemolysis)
• Stomach pain (abdominal pain)
• Headache
• Tiredness (fatigue)
• Fever or high temperature (pyrexia)
• Cough
• Urinary tract infection
• Complications related to the mandatory vaccinations
• Arm and leg pain (pain in extremities)
• Dizziness
• Joint pain (arthralgia)
• Back pain

Common (may affect up to 1 in 10 people)

• Infection in the ear, mouth or skin
• Pain in the throat
• Fewer platelets in the blood (thrombocytopenia) which may cause bleeding or bruising more easily than normal
• Nausea (feeling sick)
• Decreased levels of potassium in the blood (hypokalaemia)
• Nose bleed (epistaxis)
• Skin redness (erythema)
• Muscle pain (myalgia)
• Infection of the stomach and intestines, which may cause symptoms of mild to severe nausea, vomiting, cramps, diarrhoea (gastrointestinal infection)
• Elevated liver tests
• Difficulty breathing (dyspnoea)
• Fewer number of white blood cells (neutropenia)
• Impaired kidney function
• Different colour of the urine (chromaturia)
• High blood pressure
• Muscle spasms
• Stuffy nose (nasal congestion)
• Rash
• Infection in the blood (sepsis)
• Viral infection
• Fungal infection
• Respiratory tract infection
• Eye infection 50 – Hives
• COVID -19
• Bacterial infection
• Vaginal infection

Uncommon (may affect up to 1 in 100 people)

• Inflammation of the cervix
• Groin infection
• Pocket of pus in nose (nasal abscess)
• Pneumonia
• Tuberculosis
• Yeast infection in the oesophagus
• Pocket of pus in anus (anal abscess) Side effects reported in patients with C3G or primary IC -MPGN are listed below:

Very common (may affect more than 1 in 10 people)

• Reactions at the site of infusion
• Infection of the nose, throat, or airways (upper respiratory tract infection)
• Allergic reaction (which includes rash and eczema)
• Fever or high temperature (pyrexia)
• Headache
• Diarrhoea
• Nausea (feeling sick)
• Impaired kidney function
• Influenza

Common (may affect up to 1 in 10 people)

• Cough
• Pneumonia
• Tiredness (fatigue)
• Opportunistic infections (which include shingles and other infections that occur when the immune system is weakened)
• Urinary tract infection
• Infection in the ear
• Fewer platelets in the blood (thrombocytopenia)
• Muscle pain (myalgia)
• Nose bleed (epistaxis)
• Fewer number of white blood cells (neutropenia)
• Decreased levels of potassium in the blood (hypokalaemia)
• Arm and leg pain (pain in extremities)

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist , or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V . By reporting side effects you can help provide more information on the safety of this medicine.

🌡️ 5. How to store ASPAVELI

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date which is stated on the carton after “EXP”. The expiry date refers to the last day of that month.
• Store in a refrigerator (2 °C – 8 °C).
• Keep the vial in the original carton in order to protect it from light.

51 • Do not throw away any medicines via wastewater. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

📦 6. Contents of the pack and other information

What ASPAVELI contains

The active substance is pegcetacoplan 1 080 mg (54 mg/mL in a 20 mL vial).

The other ingredients are : sorbitol (E 420) (see section 2 “ASPAVELI contains sorbitol”), g lacial acetic acid , sodium acetate trihydrate (see section 2 “ASPAVELI contains sodium”) , sodium hydroxide (see section 2 “ASPAVELI contains sodium”), and water for injection s.

What ASPAVELI looks like and contents of the pack

ASPAVELI is a clear, colourless to slightly yellowish solution for subcutaneous infusion (54 mg/mL in a 20 mL vial). Solutions that are cloudy or have particles or colour change should not be used.

Pack sizes ASPAVELI is available in packs containing 1 vial and in multipack s comprising 8 cartons, each containing 1 vial.

Please note that alcohol swabs, needles, and other supplies or equipment are not contained in the pack.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Swedish Orphan Biovitrum AB (publ) SE-112 76 Stockholm Sweden

Manufacturer

Swedish Orphan Biovitrum AB (publ) Norra Stationsgatan 93 113 64 Stockholm Sweden This leaflet was last revised in .

Other sources of information Detailed information on this medicine is available on the European Medicines Agency web site: https://www.ema.europa.eu . There are also links to other websites about rare diseases and treatments.

📄 Package Leaflet – official source

This article reproduces the information in the official package leaflet, as authorised in the European Union. You can consult the original document here: Product information ASPAVELI (PDF, ec.europa.eu).

You can check this medicine at any time in the Union Register of medicinal products (EU number EU/1/21/1595).

⚠️ Important: This article is for information purposes only and does not replace medical advice or the package leaflet inside the medicine box. Read the leaflet carefully before use. For any questions about your treatment, talk to your doctor or pharmacist. If you experience side effects, tell your doctor or pharmacist and report them through your national reporting system.