Evkeeza

Package leaflet: Information for the patient

Evkeeza 150 mg/mL concentrate for solution for infusion

evinacumab
Medicinal product subject to additional monitoring. This will allow for rapid identification of
new safety information. You can help by reporting any adverse reactions you experience while
taking this medicine. See the end of section 4 for information on how to report adverse reactions.
Please read all of this leaflet carefully before you start using this medicine, as it contains important
information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or nurse.
• If you experience any adverse reactions, including those not listed in this leaflet, talk to your doctor or nurse. See section 4.

Contents of this leaflet

1. What Evkeeza is and what it is used for
2. What you need to know before taking Evkeeza
3. How to take Evkeeza
4. Possible side effects
5. How to store Evkeeza
6. Contents of the pack and other information

1. What Evkeeza is and what it is used for

What Evkeeza is
Evkeeza contains the active substance evinacumab. It is a type of medicine called a "monoclonal antibody". Monoclonal antibodies are proteins that bind to other substances in the body.

What Evkeeza is used for
Evkeeza is used to treat adults and children aged 6 months and older who have very high cholesterol caused by a condition called "homozygous familial hypercholesterolaemia". Evkeeza is used together with a low-fat diet and other cholesterol-lowering medicines.

Homozygous familial hypercholesterolaemia is an inherited condition, usually passed down from both the father and the mother.

People with this condition have extremely high levels of LDL-C ("bad cholesterol") from birth. Such high levels can lead to heart attacks, heart valve disease, or other problems at a young age.

How Evkeeza works
Evinacumab, the active substance in Evkeeza, binds to a protein in the body called ANGPTL3 and blocks its effects. ANGPTL3 is involved in regulating cholesterol production, and blocking its effect reduces cholesterol production. In this way, Evkeeza lowers LDL cholesterol levels in the blood and thereby helps prevent complications caused by high LDL-C levels.

2. What you should know before taking Evkeeza

Evkeeza must not be administered to you if:

• you are allergic to evinacumab or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Please speak to your doctor or nurse before receiving Evkeeza.
Pay attention to serious side effects
Evkeeza may cause serious allergic reactions.

• Immediately inform your doctor or nurse if you experience any symptoms of a severe allergic reaction. Symptoms are listed under 'Serious side effects' in section 4.

Children
Evkeeza is not recommended for children under 6 months of age, as sufficient information on its use in this patient group is not yet available.
Other medicines and Evkeeza
Inform your doctor if you are taking, have recently taken, or might take any other medicines.
Pregnancy and contraception
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or are breastfeeding, consult your doctor before taking this medicine.

• Evkeeza may harm the unborn child.
• Inform your doctor immediately if you become pregnant during treatment with Evkeeza.

Women of childbearing potential must use an effective method of contraception to avoid becoming pregnant.

• Use an effective contraceptive method during treatment with Evkeeza.
• Continue using effective contraception for at least 5 months after the last dose of Evkeeza. Speak to your doctor to determine the most appropriate contraceptive method during this period.

Breastfeeding

• If you are breastfeeding or plan to breastfeed, consult your doctor for advice before receiving this medicine.
• It is not known whether Evkeeza passes into breast milk.

Driving and using machines
Evkeeza may cause dizziness and fatigue, which could affect your ability to ride a bicycle, drive vehicles, or operate tools or machinery. If you think you are affected, do not ride a bicycle, drive, or use tools or machinery, and inform your doctor (see section 4).
Evkeeza contains proline
This medicine contains 30 mg of proline per mL. Proline may be harmful for patients with hyperprolinemia, a rare genetic disorder characterized by accumulation of proline in the body. If you (or your child) have hyperprolinemia, do not use this medicine unless recommended by your doctor.
Evkeeza contains polysorbate 80
This medicine contains 1 mg of polysorbate 80 per mL. Polysorbates may cause allergic reactions. Inform your doctor if you (or your child) have known allergies.

3. How to take Evkeeza

How much Evkeeza to take
Your doctor will determine the amount of medicine to administer. The amount will depend on your
body weight.

• The recommended dose is 15 milligrams per kilogram of body weight.
• The medicine will be administered approximately once a month.

How to take Evkeeza
Evkeeza is usually administered by a doctor or nurse as an intravenous infusion (IV) into a vein over 60 minutes.
If you miss a dose of Evkeeza
If you have missed an appointment to receive Evkeeza, contact your doctor or nurse as soon as
possible.
If you have any doubts about how to use this medicine, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
Serious side effects
Severe allergic reactions (uncommon: may affect up to 1 in 100 people)
Immediately inform your doctor or nurse if you experience any of the following symptoms of a severe
allergic reaction (anaphylactic reaction). The infusion will be stopped immediately and you may
need to take other medicines to control the reaction:

• swelling – mainly of the lips, tongue or throat, which may cause difficulty in swallowing or breathing
• breathing problems or wheezing
• feeling dizzy or faint
• skin rash, hives
• itching sensation.

Other side effects
Inform your doctor or nurse if you notice any of the following side effects.
Very common (may affect more than 1 in 10 people)

• symptoms of the common cold, such as runny nose, sore throat and cough (nasopharyngitis).

Common (may affect up to 1 in 10 people)

• sore throat or sinusitis (upper respiratory tract infection)
• dizzinessnausea
• stomach pain
• constipation
• back pain
• pain in hands or feet (limb pain)
• flu-like symptoms
• feeling tired or fatigued (asthenia)
• infusion-related reaction, such as itching at the site where the infusion is administered, redness, skin rash or chills.

Other side effects in children aged between 5 and 11 years
Very common (may affect more than 1 in 10 people)

• feeling tired (fatigue)

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or nurse.
You can also report side effects directly via the national reporting system detailed in Annex V. Reporting
side effects can help provide more information on the safety of this medicine.

5. How to store Evkeeza

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 and vial after EXP. The expiry date refers to the last day of that month.
Store in a refrigerator (2 ºC – 8 ºC).
Do not freeze. Do not shake.
Keep in the original packaging to protect the medicine from light.
Do not use this medicine if it appears cloudy, has changed colour, or contains particulate matter.
Do not store any unused portion of the infusion solution for reuse later. Any unused portion of the infusion solution must not be reused and should be disposed of according to local requirements.

6. Package contents and other information

What Evkeeza contains

• The active substance is evinacumab. Each mL of concentrate for infusion solution contains 150 mg of evinacumab.

Each vial contains 345 mg of evinacumab in 2.3 mL of concentrate or 1,200 mg of evinacumab
in 8 mL of concentrate.

• The other components are proline, arginine hydrochloride, histidine hydrochloride monohydrate, polysorbate 80, histidine, and water for injections. See section 2, ‘Evkeeza contains proline’ and ‘Evkeeza contains polysorbate 80’.

Description of the appearance of Evkeeza and contents of the pack
Evkeeza concentrate for infusion solution is a solution ranging from clear to slightly opalescent, colourless to pale yellow.
It is available in packs containing 1 glass vial of 2.3 mL concentrate or 1 glass vial of 8 mL concentrate.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Ultragenyx Germany GmbH
Rahel-Hirsch-Str. 10
10557 Berlin
Germany

Manufacturer
Ultragenyx Netherlands B.V.
Evert van de Beekstraat 1, Unit 104
1118 CL Schiphol
The Netherlands

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

BE, BG, CZ, DK, DE, EE, ES, HR, IE, IS, IT, CY, LI, LV, LT, LU, HU, MT, NL, NO, AT, PL, PT, RO, SI, SK, FI, SE
Ultragenyx Germany GmbH, DE
Tel/Tél/Teл./Tlf/Puh/Sími: +49 30 20179810

EL
Medison Pharma Greece Single Member Societe Anonyme, EL
Tel: +30 210 0100 188

FR
Ultragenyx France SAS, FR
Tel: +33 1 85 65 37 61 or 0800 91 79 24 (toll-free number)

This medicinal product has been granted a marketing authorisation under “exceptional circumstances”. This means that, due to the rarity of the disease, it has not been possible to obtain complete information about this medicinal product. The European Medicines Agency will review any new information on this medicinal product annually, and this patient information leaflet will be updated as necessary.

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu

The following information is intended for healthcare professionals only:

Traceability
In order to improve the traceability of biological medicinal products, the name and batch number of the administered medicinal product must be clearly documented.

Instructions for use
Preparation of the solution
Evkeeza is supplied as a single-use vial only. A strict aseptic technique must be used during preparation and reconstitution.

• Visually inspect the medicinal product for turbidity, discoloration, or particulate matter prior to administration.
• Discard the vial if the solution is cloudy or discolored, or contains particulate matter.
• Do not shake the vial.
• Withdraw the required volume of evinacumab from the vial(s) based on the patient's body weight and transfer it into an intravenous infusion bag containing sodium chloride 9 mg/mL (0.9%) or dextrose 50 mg/mL (5%) for infusion. Gently invert the bag to mix the diluted solution.
• For patients weighing 45 kg or more, the intravenous infusion bag must contain a maximum volume of 250 mL of sodium chloride 9 mg/mL (0.9%) or dextrose 50 mg/mL (5%).
• For patients weighing between 26 kg and 44 kg, the intravenous infusion bag must contain a maximum volume of 150 mL of sodium chloride 9 mg/mL (0.9%) or dextrose 50 mg/mL (5%).
• For patients weighing between 3 kg and 25 kg, the intravenous infusion bag must contain a maximum volume of 5 mL/kg. The corresponding volume for patients weighing between 3 kg and 25 kg should range from 15 mL to 125 mL of sodium chloride 9 mg/mL (0.9%) or dextrose 50 mg/mL (5%), administered at a maximum rate of 5 mL/kg/hour.
• Do not freeze or shake the solution.
• Discard any unused portion remaining in the vial.

Any unused medicinal product and waste material must be disposed of in accordance with local regulations.

After dilution
Once prepared, the diluted solution should be administered immediately. If immediate administration is not possible, the diluted solution may be stored temporarily:

• in a refrigerator at 2 °C to 8 °C for up to 24 hours from the time of preparation to the end of infusion, or
• at room temperature up to 25 °C for a maximum of 6 hours from the time of preparation to the end of infusion.

Administration

• If refrigerated, allow the solution to reach room temperature (up to 25 °C) before administration.
• Evinacumab must be administered over 60 minutes via intravenous infusion through an intravenous line equipped with a sterile in-line or add-on filter of 0.2 to 5 microns. Do not administer evinacumab as an intravenous push or bolus.
• Do not mix other medicinal products with evinacumab or administer them simultaneously through the same infusion line.

The infusion rate may be slowed, interrupted, or stopped if the patient develops any signs of adverse reactions, including infusion-related symptoms.