Imlygic

Package leaflet: Information for the patient

Imlygic 10 plaque-forming units (PFU)/mL injectable solution, 10 plaque-forming units (PFU)/mL injectable solution

talimogene laherparepvec
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your healthcare provider (doctor or nurse).
• If you experience any side effects, including those not listed in this leaflet, inform your healthcare provider. See section 4.
• Your doctor will provide you with a Patient Alert Card. Read it carefully and follow the instructions provided.
• Always show your Patient Alert Card to your doctor or nurse during visits or when you go to hospital.

Contents of this leaflet

1. What Imlygic is and what it is used for
2. What you need to know before using Imlygic and during treatment with Imlygic
3. How Imlygic is administered
4. Possible side effects
5. How to store Imlygic
6. Contents of the pack and other information

1. What Imlygic is and what it is used for

Imlygic is used for the treatment of adult patients with a type of skin cancer called
melanoma in which the disease has spread to the skin or lymph nodes and is not surgically removable.
The active substance of Imlygic is talimogene laherparepvec. This is a weakened form of herpes simplex virus type 1 (HSV-1), commonly known as the cold sore virus. Imlygic is produced by introducing certain modifications into the HSV-1 virus, enabling it to replicate more effectively within tumour cells rather than in healthy cells, thereby leading to the destruction of infected tumour cells. This medicine also works by helping the immune system recognize and destroy tumours present in the body.

2. What you should know before using Imlygic and during treatment with Imlygic

Imlygic will not be administered to you:

• if you are allergic to talimogene laherparepvec or to any of the other ingredients of this medicinal product (listed in section 6).
• if your healthcare provider has informed you that your immune system is severely weakened.

Warnings and precautions
Speak to your healthcare provider before receiving this medicine.
Life-threatening herpes infections
Life-threatening herpes infections that spread to other parts of the body distant from the injection site (disseminated herpes infection) may occur. If you develop new or worsening symptoms, inform your healthcare provider immediately. Inform your healthcare provider if you have or have ever had a weakened immune system, if you have HIV/AIDS, if you have a blood or bone marrow cancer, or if you are taking steroids or other medicines that suppress the immune system, as you may be at increased risk of life-threatening herpes infections.
Accidental spread of Imlygic to yourself and others
Imlygic may spread to other parts of your body or to other people through direct contact with bodily fluids or injection sites.
You must do the following to prevent the spread of Imlygic to other parts of your body or to people in close contact with you (e.g. family members, caregivers, sexual partners, or individuals with whom you share a bed):

• Avoid allowing people in close contact with you to come into direct contact with your injection sites or bodily fluids (e.g. blood and urine) during treatment with this medicine and for 30 days after the last dose (e.g. by using latex condoms during sexual intercourse or avoiding kissing if either partner has mouth ulcers).
• Avoid touching or scratching the injection sites.
• Always keep the injection sites covered with waterproof, airtight dressings. Apply the dressing according to instructions provided by your healthcare provider. If the dressing becomes loose or falls off, replace it immediately with a clean dressing.
• Dispose of all used dressings and cleaning materials in a sealed plastic bag and throw them in household waste.

You must inform people in close contact with you to:

• Avoid direct contact with your bodily fluids or injection sites.
• Wear gloves when changing dressings.

If people in close contact with you are accidentally exposed to Imlygic, they should clean the exposed area of the body with water and soap and/or a disinfectant. If they develop signs or symptoms of a herpes infection, you should advise them to contact a doctor. If herpes lesions (blisters or ulcers) are suspected, patients or their close contacts may undergo further testing by the Marketing Authorization Holder for additional characterization of the infection. Discuss this with your healthcare provider.
If people in close contact with you are pregnant, have a weakened immune system, or if newborns are present
Ensure that people in close contact with you who are pregnant or have a weakened immune system do not touch the injection sites, used dressings, or cleaning materials. Keep newborns away from used dressings and cleaning materials.
Herpes infection
During or after treatment with Imlygic, you may develop cold sores or more severe herpes infections. Signs and symptoms related to Imlygic treatment may resemble those of a herpes infection, including but not limited to the development of a painful, burning, or tingling blister around the mouth, genitals, fingers, or ears, eye pain, light sensitivity, eye discharge or blurred vision, weakness in arms or legs, extreme drowsiness (feeling of falling asleep), and mental confusion. If you experience any of these signs or new symptoms, you should follow standard hygiene precautions to prevent virus transmission to others. If herpes lesions (blisters or ulcers) are suspected, patients or their close contacts may undergo further testing by the Marketing Authorization Holder for additional characterization of the infection. Discuss this with your healthcare provider.
Infection and delayed healing at the injection site
Imlygic may cause infection at the injection site. Signs and symptoms of infection include pain, redness, warmth, swelling, discharge, or ulcer formation, fever, and chills. Healing at the injection site may take longer than usual. If you notice any of these symptoms, inform your healthcare provider.
Autoimmune reactions
Imlygic may cause autoimmune reactions (i.e. an overreaction of the immune system). Some patients treated with this medicine have developed kidney inflammation (glomerulonephritis), narrowing or blockage of blood vessels (vasculitis), lung edema (pneumonitis), worsening of skin peeling (psoriasis), and areas of skin without pigmentation (vitiligo). If you have a history of autoimmune disease, inform your healthcare provider.
Plasmacytoma
Imlygic may cause accumulation of malignant white blood cells at or near the injection site (plasmacytoma). If you have a history of blood cell cancer, including multiple myeloma, inform your healthcare provider.
Difficulty breathing
If you have a neck tumor, your healthcare provider may warn you about a possible sensation of airway compression during treatment.
Children and adolescents
The use of Imlygic has been studied in children and young adults aged 7 to ≤ 21 years with advanced non-central nervous system tumors suitable for direct injection. The use of Imlygic has not been studied in children under 7 years of age.
Other medicines and Imlygic
Inform your healthcare provider if you are taking, have recently taken, or might take any other medicines, including those used to treat or prevent herpes infections, such as aciclovir.
Aciclovir and other antiviral treatments may reduce the effects of Imlygic.
Pregnancy and breastfeeding
Talk to your healthcare provider if:

• you suspect you are pregnant; or
• you are planning a pregnancy. Your healthcare provider will determine whether Imlygic is suitable for you.

If you are pregnant or breastfeeding, ask your healthcare provider for advice before receiving this medicine. Imlygic may be harmful to the fetus.
Women of childbearing potential must use an effective method of contraception to prevent pregnancy during treatment with Imlygic. Speak to your healthcare provider for information on suitable contraceptive methods.
It is not known whether Imlygic passes into breast milk. It is important that you inform your healthcare provider if you are breastfeeding or plan to breastfeed. In such cases, you will be assisted in deciding whether to discontinue breastfeeding or Imlygic treatment, taking into account the benefit of breastfeeding for the child and the benefit of Imlygic for you.
Driving and use of machines
During treatment with Imlygic, you may experience symptoms such as dizziness or confusion, which may impair your ability to drive or operate machinery. Exercise caution when driving or using machines until you are certain that this medicine does not cause undesirable effects in you.
Imlygic contains sodium and sorbitol
This medicine contains 7.7 mg of sodium (a main component of table salt) per 1 mL vial. This corresponds to 0.4% of the maximum daily recommended dietary intake for an adult.
This medicine contains 20 mg of sorbitol per 1 mL vial.

3. How Imlygic is administered

This medicine is administered in a healthcare setting under the supervision of a healthcare professional.
The recommended initial dose is up to 4 mL of Imlygic at a concentration of 10^6 (1 million) PFU/mL.
Subsequent doses will be up to 4 mL of Imlygic at a concentration of 10^8 (100 million) PFU/mL.

The healthcare professional will inject this medicine directly into the tumor(s) using a needle and syringe.
The second injection will be given 3 weeks after the first injection. After that, the medicine will be injected
every 2 weeks for as long as tumors are present.

The healthcare professional will determine which tumor(s) should be treated and may decide not to inject
the medicine into all tumors. It is possible that the size of existing tumors may increase and that one or
more new tumors may appear during treatment with Imlygic.

Treatment with Imlygic should last at least 6 months, but may continue longer.

If you miss a dose of Imlygic
It is important that you attend all scheduled appointments for administration of this medicine.
If you miss an appointment, contact your healthcare professional to schedule the next dose.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Keeping wounds clean and protected with dressings may help prevent the development of bacterial infections (cellulitis) at the injection site.
Influenza-like illness, fever, and chills have been observed in patients treated with Imlygic. These symptoms usually resolve within 72 hours after treatment.
The following side effects have been reported in patients treated with Imlygic:

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

• Swelling of tissues (peripheral edema)
• Headache
• Cough
• Vomiting, diarrhea, constipation, nausea
• Muscle pain (myalgia), joint pain/swelling (arthralgia), limb pain
• Influenza-like illness, fever (pyrexia), chills, fatigue, pain
• Pain, redness, bleeding, swelling, inflammation, discharge, leakage, and warmth at the injection site

Common (may affect up to 1 in 10 people):

• Bacterial infection (cellulitis), cold sores (herpes labialis)
• Pain at tumor site, infection of tumor lesion
• Tiredness, headaches, dizziness, paleness (reduced red blood cell count - anemia)
• Immune system-related side effects:
  • fever, fatigue, weight loss, muscle and joint pain (narrowing or blockage of blood vessels - vasculitis)
  • shortness of breath, cough, fatigue, loss of appetite, unintended weight loss (inflammation of the lungs - pneumonia)
  • increase in skin plaques that appear dry, red, and covered with silvery scales (worsening of skin shedding - worsening of psoriasis)
  • pink or brown urine, foamy urine, high blood pressure, fluid retention (inflammation of the kidneys - glomerulonephritis)
• Dehydration
• Confusion, anxiety, depression, dizziness, difficulty sleeping (insomnia)
• Pain in the ear, throat, abdomen, groin, back, or under the arm
• Faster resting heart rate (tachycardia)
• Pain, swelling, warmth, and tenderness in one leg or arm due to blood clot in a vein (deep vein thrombosis), high blood pressure (hypertension), facial redness (flushing)
• Shortness of breath (dyspnea), upper respiratory tract infection
• Abdominal discomfort
• Areas of skin without pigmentation (vitiligo), rash, inflamed skin (dermatitis)
• General feeling of being unwell
• Weight loss
• Wound-related complications, discharge, bruising (contusion), pain after procedure

Uncommon (may affect up to 1 in 100 people):

• Infection at the incision site
• Malignant white blood cell tumor growing at or near the injection site (plasmacytoma)
• Herpes-related eye infection (herpetic keratitis)
• Airway compression (airway obstructive disorder)
• Allergic reaction (hypersensitivity)

Reporting of side effects
If you get any side effects, including ones not listed in this leaflet, talk to your healthcare provider. You can also report side effects directly through the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Imlygic

Storage of Imlygic will be handled by healthcare professionals at the treatment facility.
Do not use this medicine after the expiry date stated on the label and carton after "Exp". The expiry date refers to the last day of that month.
Store and transport in a freezer at a temperature between -90°C and -70°C.
Keep in the original carton to protect the medicine from light.
This medicine contains genetically modified organisms. Follow local guidelines.

6. Package contents and other information

What Imlygic contains

• The active substance is talimogene laherparepvec. Each vial contains 1 mL of solution with a nominal concentration of 1 × 10^6 (1 million) plaque-forming units (PFU)/mL or 1 × 10^8 (100 million) PFU/mL.
• The other components are disodium phosphate dihydrate, sodium dihydrogen phosphate dihydrate, sodium chloride, myo-inositol, sorbitol (E420), water for injections (see section 2).

Description of the appearance of Imlygic and contents of the pack
Imlygic is a liquid, from clear to slightly opalescent (1 × 10^6 PFU/mL) or from slightly opalescent to
opaque (1 × 10^8 PFU/mL). It is supplied as a 1 mL solution, preservative-free, in a single-use vial
(made of cyclic olefin polymer plastic resin) with a stopper (chlorobutyl rubber) and seal (aluminum) with a flip-off cap (polypropylene).
The vial cap is colour-coded: light green for the 1 × 10^6 PFU/mL vial and royal blue for the 1 × 10^8 PFU/mL vial.

Marketing Authorisation Holder and Manufacturer
Amgen Europe B.V.
Minervum 7061
4817 ZK Breda
The Netherlands

Marketing Authorisation Holder
Amgen Europe B.V.
Minervum 7061
4817 ZK Breda
The Netherlands

Manufacturer
Amgen NV
Telecomlaan 5-7
1831 Diegem
Belgium

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

België/Belgique/Belgien Lietuva
s.a. Amgen n.v. Amgen Switzerland AG Vilniaus filialas
Tél/Tel: +32 (0)2 7752711 Tel: +370 5 219 7474

България Luxembourg/Luxemburg
Амджен България ЕООД s.a. Amgen
Тел.: +359 (0)2 424 7440 Belgique/Belgien
Tél/Tel: +32 (0)2 7752711

Česká republika Magyarország
Amgen s.r.o. Amgen Kft.
Tel: +420 221 773 500 Tel.: +36 1 35 44 700

Danmark Malta
Amgen, filial af Amgen AB, Sverige Amgen S.r.l.
Tlf: +45 39617500 Italy
Tel: +39 02 6241121

Deutschland Nederland
Amgen GmbH Amgen B.V.
Tel.: +49 89 1490960 Tel: +31 (0)76 5732500

Eesti Norge
Amgen Switzerland AG Vilniaus filialas Amgen AB
Tel: +372 58609553 Tlf: +47 23308000

Ελλάδα Österreich
Amgen Ελλάς Φαρμακευτικά Ε.Π.Ε. Amgen GmbH
Τηλ: +30 210 3447000 Tel: +43 (0)1 50 217

España Polska
Amgen S.A. Amgen Biotechnologia Sp. z o.o.
Tel: +34 93 600 18 60 Tel.: +48 22 581 3000

France Portugal
Amgen S.A.S. Amgen Biofarmacêutica, Lda.
Tél: +33 (0)9 69 363 363 Tel: +351 21 4220606

Hrvatska România
Amgen d.o.o. Amgen România SRL
Tel: +385 (0)1 562 57 20 Tel: +4021 527 3000

Ireland Slovenija
Amgen Ireland Limited AMGEN zdravila d.o.o.
Tel: +353 1 8527400 Tel: +386 (0)1 585 1767

Ísland Slovenská republika
Vistor hf. Amgen Slovakia s.r.o.
Sími: +354 535 7000 Tel: +421 2 321 114 49

Italia Suomi/Finland
Amgen S.r.l. Amgen AB, sivuliike Suomessa/Amgen AB, filial
Tel: +39 02 6241121 i Finland
Puh/Tel: +358 (0)9 54900500

Kύπρος Sverige
C.A. Papaellinas Ltd Amgen AB
Τηλ: +357 22741 741 Tel: +46 (0)8 6951100

Latvija United Kingdom (Northern Ireland)
Amgen Switzerland AG Rīgas filiāle Amgen Limited
Tel: +371 25725888 Tel: +44 (0)1223 420305

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

The following information is intended exclusively for healthcare professionals:

This medicinal product contains genetically modified organisms. During preparation or administration of talimogene laherparepvec, use personal protective equipment (e.g., protective gown or laboratory coat, safety goggles or face mask, and gloves).
After administration, change gloves before applying the occlusive dressing to the injected lesions. Clean the external surface of the occlusive dressing using an alcohol-impregnated wipe. It is recommended to keep injection sites covered with occlusive, waterproof, and airtight dressings whenever possible.

Thawing of Imlygic vials

• Before use, thaw frozen vials at room temperature (between 20 °C and 25 °C) until Imlygic becomes liquid. The expected time to achieve complete thawing ranges from 30 to 70 minutes, depending on room temperature. Gently rotate. DO NOT shake.
• Vials must be thawed and stored in their original carton until the time of administration to protect the medicinal product from light.

After thawing

• After thawing, administer Imlygic as soon as practically possible.
• Thawed Imlygic is stable when stored at 2°C to 25°C, protected from light, in its original vial, in a syringe, or in its original vial and subsequently in a syringe. Do not exceed the storage times specified in Table 1 and Table 2.
• If storing thawed Imlygic in its original vial and subsequently transferring it to a syringe:
  • The same temperature range must be maintained throughout the storage period until administration.
  • The storage time in the syringe at room temperature up to 25°C must not exceed 2 hours for 10⁶ (1 million) PFU/mL and 4 hours for 10⁸ (100 million) PFU/mL (see Table 1).
  • The maximum cumulative storage time (storage time in vial plus storage time in syringe) must not exceed the durations listed in Table 2.
• Imlygic must not be refrozen after thawing. Discard thawed Imlygic in the vial or in the syringe if stored longer than the specified times.

Table 1: Maximum storage time of thawed Imlygic in a syringe

Table 2: Maximum cumulative storage time (vial storage time plus syringe storage time) for thawed Imlygic

Unused medicine and waste material from such medicine must be disposed of in accordance with local applicable regulations.