Imlygic

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 
 
 
 
 
 



 

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This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Imlygic 106 plaque forming units (PFU)/mL solution for injection 
Imlygic 108 plaque forming units (PFU)/mL solution for injection 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
2.1 General description 
 
Talimogene laherparepvec is an attenuated herpes simplex virus type-1 (HSV-1) derived by functional 
deletion of 2 genes (ICP34.5 and ICP47) and insertion of coding sequence for human granulocyte 
macrophage colony-stimulating factor (GM-CSF) (see section 5.1). 
 
Talimogene laherparepvec is produced in Vero cells by recombinant DNA technology. 
 
2.2 Qualitative and quantitative composition 
 
Imlygic 106 plaque forming units (PFU)/mL solution for injection 
 
Each vial contains 1 mL deliverable volume of Imlygic at a nominal concentration of 1 x 106 
(1 million) plaque forming units (PFU)/mL 
 
Imlygic 108 plaque forming units (PFU)/mL solution for injection 
 
Each vial contains 1 mL deliverable volume of Imlygic at a nominal concentration of 1 x 108 
(100 million) plaque forming units (PFU)/mL. 
 
Excipient with known effect 
 
Each 4 mL dose contains approximately 30 mg (1.3 mmol) sodium and 80 mg sorbitol. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection. 
 
Imlygic 106 plaque forming units (PFU)/mL solution for injection 
 
Clear to semi-translucent liquid following thaw from its frozen state. 
 
It may contain white, visible, variously shaped, virus-containing particles. 
 
Imlygic 108 plaque forming units (PFU)/mL solution for injection 
 
Semi-translucent to opaque liquid following thaw from its frozen state. 
 
It may contain white, visible, variously shaped, virus-containing particles. 
 
 



 

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4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Imlygic is indicated for the treatment of adults with unresectable melanoma that is regionally or 
distantly metastatic (Stage IIIB, IIIC and IVM1a) with no bone, brain, lung or other visceral disease 
(see sections 4.4 and 5.1). 
 
4.2 Posology and method of administration 
 
Treatment with talimogene laherparepvec should be initiated and supervised by a qualified physician 
experienced in the treatment of cancer. 
 
Patients treated with Imlygic must be given the patient alert card and be informed about the risks of 
Imlygic (see also package leaflet). 
 
Posology 
 
Imlygic is provided in single use vials of 1 mL each in two different concentrations: 
 106 (1 million) PFU/mL - For initial dose only. 
 108 (100 million) PFU/mL - For all subsequent doses. 
 
The total injection volume for each treatment visit should be up to a maximum of 4 mL. The initial 
recommended dose is up to a maximum of 4 mL of Imlygic at a concentration of 
106 (1 million) PFU/mL. Subsequent doses should be administered up to 4 mL of Imlygic at a 
concentration of 108 (100 million) PFU/mL. 
 
The recommended dosing schedule for Imlygic is shown in table 1. 
 
Table 1. Recommended dosing schedule for Imlygic 
 

Treatment 
visit 

Treatment 
interval 

Maximum 
total 

injection 
volume 

Dose 
concentrations

Prioritisation of lesions to be 
injected 

Initial - Up to 4 mL 
106  

(1 million) 
PFU/mL 

 Inject largest lesion(s) first. 
 Prioritise injection of 

remaining lesions based on 
lesion size until maximum 
injection volume is reached.

Second 3 weeks after initial treatment Up to 4 mL 
108  

(100 million) 
PFU/mL 

 First inject any new lesions 
(lesions that may have 
developed since initial 
treatment). 

 Prioritise injection of 
remaining lesions based on 
lesion size until maximum 
injection volume is reached. 



 

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Treatment 
visit 

Treatment 
interval 

Maximum 
total 

injection 
volume 

Dose 
concentrations

Prioritisation of lesions to be 
injected 

All subsequent 
treatment 

visits 
(including re-

initiation) 

2 weeks after 
previous 
treatment 

Up to 4 mL 
108  

(100 million) 
PFU/mL 

 First inject any new lesions 
(lesions that may have 
developed since previous 
treatment). 

 Prioritise injection of 
remaining lesions based on 
lesion size until maximum 
injection volume is reached. 

 
Determining Imlygic dose volume (per lesion) 
 
The volume of Imlygic to be injected into each lesion is dependent on the size of the lesion and should 
be determined according to table 2. The total injection volume for each treatment session should be up 
to a maximum of 4 mL. 
 
Table 2. Selection of Imlygic injection volume based on lesion size 
 
Lesion size  
(longest dimension) Imlygic injection volume 

> 5 cm  up to 4 mL 

> 2.5 cm to 5 cm  up to 2 mL  

> 1.5 cm to 2.5 cm  up to 1 mL  

> 0.5 cm to 1.5 cm  up to 0.5 mL  

≤ 0.5 cm  up to 0.1 mL  
 
Patients may experience increase in size of existing lesion(s) or the appearance of a new lesion prior to 
achieving a response. As long as there are injectable lesion(s) remaining, Imlygic should be continued 
for at least 6 months unless the physician considers that the patient is not benefitting from Imlygic 
treatment or that other treatment is required. 
 
Imlygic treatment may be reinitiated if new lesions appear following a complete response and the 
physician considers that the patient will benefit from treatment. 
 
Special populations 
 
Paediatric population 
 
The safety and efficacy of Imlygic in paediatric patients has not been established. No data are 
available. 
 
Elderly population 
 
No adjustment of the dose is required in patients ≥ 65 years old (see section 5.1). 
 



 

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Hepatic and renal impairment 
 
No clinical studies have been conducted to evaluate the effect of hepatic or renal impairment on the 
pharmacokinetics of talimogene laherparepvec. However, no adjustment in dosage is necessary for 
patients with hepatic or renal impairment. 
 
Method of administration 
 
Imlygic is to be administered by intralesional injection into cutaneous, subcutaneous, and/or nodal 
lesions that are visible, palpable or detectable by ultrasound guidance. 
 
If healthcare professionals are accidentally exposed to Imlygic, see sections 4.4 and 6.6. 
 
Healthcare professionals who are immunocompromised or pregnant should not administer Imlygic and 
should not come into direct contact with the Imlygic injection site(s) or body fluids of treated patients 
(see sections 4.3 and 4.4). 
 
Follow the instructions below to prepare and administer Imlygic to patients: 
 
Pre-injection 
 Thaw Imlygic vial(s) at room temperature. Thawed Imlygic may be stored prior to 

administration (see section 6.3). 
 Draw the desired amount of Imlygic from the vial into a syringe using aseptic technique. A 22- 

to 26-gauge needle is recommended. 
 The injection site may be treated with a topical anaesthetic agent. Injectable anaesthetic may be 

injected around the periphery of the lesion but should not be injected directly into the lesion. 
 Clean the lesion and surrounding areas with an alcohol swab and let dry. 
 
Injection 
 Inject Imlygic intralesionally into cutaneous, subcutaneous, and/or nodal lesions that are visible, 

palpable or detectable by ultrasound guidance. 
 Determine injection volume for each lesion using table 2 above. 
 Using a single insertion point, inject Imlygic along multiple tracks as far as the radial reach of 

the needle allows within the lesion to achieve even and complete dispersion. Multiple insertion 
points may be used if a lesion is larger than the radial reach of the needle. 

 
Cutaneous lesions Subcutaneous lesions Nodal lesions 

 
  

Figure 1. 
Injection administration for 
cutaneous lesions 

Figure 2. 
Injection administration for 
subcutaneous lesions 

Figure 3. 
Injection administration for 
nodal lesions  

 
 Disperse Imlygic evenly and completely within the lesion by pulling the needle back without 

exiting the lesion. Redirect the needle as many times as necessary while injecting the remainder 
of the dose of Imlygic. Continue until the full dose is evenly and completely dispersed. 

 When removing the needle, withdraw it from the lesion slowly to avoid leakage or splash back 
of Imlygic at the insertion point. 



 

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 Repeat these steps for other lesions that need to be injected. Use a new needle anytime the 
needle is completely removed from a lesion and each time a different lesion is injected. 

 
Post-injection 
 Apply pressure to the injection site with a sterile gauze for at least 30 seconds. 
 Swab the injection site and surrounding area with alcohol, and cover the injected lesion with an 

absorbent pad and dry occlusive dressing. 
 
Disposal 
Dispose of all materials that have come in contact with Imlygic (e.g. vial, syringe, needle, any cotton 
or gauze) in accordance with local institutional procedures (see section 6.6). 
 
4.3 Contraindications 
 
 Patients with a history of hypersensitivity to talimogene laherparepvec or any of its excipients. 
 Patients who are severely immunocompromised (e.g. patients with severe congenital or acquired 

cellular and/or humoral immune deficiency) (see section 4.4). 
 
4.4 Special warnings and precautions for use 
 
Previously treated patients 
 
Efficacy data for Imlygic in the current second or later line treatment settings are limited. 
 
Immunocompromised patients 
 
Imlygic has not been studied in immunocompromised patients. Based on animal data, patients who are 
severely immunocompromised may be at an increased risk of disseminated herpetic infection and 
should not be treated with Imlygic (see sections 4.3 and 5.3). Disseminated herpetic infection may also 
occur in immunocompromised patients (such as those with HIV/AIDS, leukaemia, lymphoma, 
common variable immunodeficiency, or who require chronic high-dose steroids or other 
immunosuppressive agents). The risks and benefits of treatment should be considered before 
administering Imlygic to these patients. 
 
Accidental exposure to Imlygic 
 
Accidental exposure may lead to transmission of Imlygic and herpetic infection. Healthcare 
professionals and close contacts (e.g. household members, caregivers, sex partners or persons sharing 
the same bed) should avoid direct contact with injected lesions or body fluids of treated patients during 
the entirety of the treatment period and up to 30 days after the last treatment administration (see 
section 6.6). Accidental needle stick and splash-back have been reported in healthcare professionals 
during preparation and administration of Imlygic. 
 
Close contacts who are pregnant or immunocompromised should not change the patient’s dressing or 
clean their injection site. Pregnant women, neonates, and immunocompromised individuals should not 
be exposed to potentially contaminated materials. 
 
Healthcare professionals should ensure that patients are able to comply with the requirement to cover 
injection sites with occlusive dressings (see section 6.6). Patients should also be advised to avoid 
touching or scratching injection sites as this could lead to inadvertent transfer of Imlygic to other areas 
of their body or to their close contacts. 
 
Although it is not known if Imlygic could be transmitted through sexual contact, it is known that wild-
type HSV-1 can be transmitted through sexual contact. Patients should be advised to use a latex 
condom during sexual contact to prevent possible transmission of Imlygic. Women of childbearing 
potential should be advised to use an effective method of contraception to prevent pregnancy during 
treatment with Imlygic (see section 4.6). 



 

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Caregivers should be advised to wear protective gloves when assisting patients in applying or 
changing occlusive dressings and to observe safety precautions for disposal of used dressings and 
cleaning materials (see sections 4.2 and 6.6). 
 
In the event of an accidental exposure to Imlygic, exposed individuals should be advised to clean the 
affected area thoroughly with soap and water and/or a disinfectant. If signs or symptoms of herpetic 
infection develop, they should contact their healthcare professional. Talimogene laherparepvec is 
sensitive to acyclovir. In case suspected herpetic lesions occur, patients, close contacts or healthcare 
providers have the option of follow-up testing by the Marketing Authorisation Holder for further 
characterisation of the infection. 
 
Herpetic infection in Imlygic-treated patients 
 
In clinical studies, herpetic infections (including cold sores and herpes keratitis) have been reported in 
patients treated with Imlygic. Symptoms of a local or systemic infection possibly related to Imlygic 
are anticipated to be similar to symptoms caused by wild-type HSV-1 infections. 
 
Individuals with wild-type HSV-1 infection are known to be at a lifelong risk for symptomatic 
herpetic infection due to reactivation of latent wild-type HSV-1. Symptomatic herpetic infection due 
to possible reactivation of Imlygic should be considered. 
 
Patients who develop herpetic infections should be advised to follow standard hygienic practices to 
prevent viral transmission. 
 
Talimogene laherparepvec is sensitive to acyclovir. The risks and benefits of Imlygic treatment should 
be considered before administering acyclovir or other anti-viral agents indicated for management of 
herpetic infection. These agents may interfere with the effectiveness of Imlygic if administered 
systemically or topically directly to the injection site. 
 
Cellulitis at the injection site 
 
Necrosis or ulceration of tumour tissue may occur following Imlygic treatment. Cellulitis and systemic 
bacterial infection have been reported. Careful wound care and infection precautions are 
recommended, particularly if tissue necrosis results in open wounds. 
 
Impaired healing at the injection site 
 
In clinical studies, impaired healing at the injection site has been reported. Imlygic may increase the 
risk of impaired healing in patients with underlying risk factors (e.g. previous radiation at the injection 
site, or lesions in poorly vascularised areas). 
 
The risks and benefits of Imlygic should be considered before continuing treatment if persistent 
infection or delayed healing develops. 
 
Immune-mediated events 
 
In clinical studies, immune-mediated events including as glomerulonephritis, vasculitis, pneumonitis, 
worsening psoriasis, and vitiligo have been reported in patients treated with Imlygic. 
 
The risks and benefits of Imlygic should be considered before initiating treatment in patients who have 
underlying autoimmune disease or before continuing treatment in patients who develop immune-
mediated events. 
 



 

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Plasmacytoma at injection site 
 
Plasmacytoma has been reported in proximity to the injection site after administration of Imlygic. The 
risks and benefits of Imlygic should be considered in patients with multiple myeloma or in whom 
plasmacytoma develops during treatment. 
 
Obstructive airway disorder 
 
Obstructive airway disorder has been reported following Imlygic treatment. Caution should be used 
when injecting lesions close to major airways. 
 
HSV-1 seronegative patients 
 
Patients who were HSV-1 seronegative at baseline were reported to have a greater incidence of 
pyrexia, chills, and influenza-like illness compared with those who were HSV-1 seropositive at 
baseline, especially within the period of the first 6 treatments (see section 4.8). 
 
All patients 
 
This medicinal product contains 80 mg sorbitol (E420) per 4 mL dose. The additive effect of 
concomitantly administered products containing sorbitol (or fructose) and dietary intake of sorbitol (or 
fructose) should be taken into account. 
 
This medicinal product contains approximately 30 mg sodium per 4 mL dose, equivalent to 1.5% of 
the WHO recommended maximum daily intake of 2 g sodium for an adult. 
 
Traceability of Imlygic 
 
In order to improve the traceability of biological medicinal products, the tradename and the batch 
number of the administered product should be clearly recorded (or stated) in the patient file. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No interaction studies have been conducted with Imlygic. Acyclovir and other anti-viral agents may 
interfere with the effectiveness of Imlygic if administered systemically or topically directly to the 
injection site. Consider the risks and benefits of Imlygic treatment before administering acyclovir or 
other anti-viral agents indicated for management of herpetic infection. 
 
4.6 Fertility, pregnancy and lactation 
 
Women of childbearing potential/contraception 
 
Women of childbearing potential should be advised to use an effective method of contraception to 
prevent pregnancy during treatment with Imlygic. 
 
All patients should be advised to use a latex condom during sexual contact to prevent possible 
transmission of Imlygic (see section 4.4). 
 
Pregnancy 
 
Adequate and well controlled studies with talimogene laherparepvec have not been conducted in 
pregnant women. 
 
If a pregnant woman has an infection with wild type HSV-1 (primary or reactivation), there is 
potential for the virus to cross the placental barrier, and also a risk of transmission during birth due to 
viral shedding. Infections with wild-type HSV-1 have been associated with serious adverse effects, 
including multi-organ failure and death, if a foetus or neonate contracts the wild type herpes infection. 



 

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While there are no clinical data to date on talimogene laherparepvec infections in pregnant women, 
there could be a risk to the foetus or neonate if talimogene laherparepvec were to act in the same 
manner. No effects on embryo-foetal development have been observed in animal studies (see 
section 5.3). As a precautionary measure, it is preferable to avoid the use of talimogene laherparepvec 
during pregnancy. 
 
Transplacental metastases of malignant melanoma can occur. Because talimogene laherparepvec is 
designed to enter and replicate in the tumour tissue, there could be a risk of foetal exposure to 
talimogene laherparepvec from tumour tissue that has crossed the placenta. 
 
If Imlygic is used during pregnancy, or if the patient becomes pregnant while taking Imlygic, the 
patient should be apprised of the potential hazards to the foetus and/or neonate. 
 
Breast-feeding 
 
It is unknown whether talimogene laherparepvec is transferred into human milk. A decision must be 
made whether to discontinue breast-feeding or to discontinue/abstain from Imlygic therapy taking into 
account the benefit of breast-feeding for the child and the benefit of therapy for the woman. 
 
Fertility 
 
No clinical studies have been performed to evaluate the effects of talimogene laherparepvec on 
fertility (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Talimogene laherparepvec may have a minor influence on the ability to drive and use machines. 
Because of potential adverse reactions such as dizziness and confusional state (see section 4.8), 
patients should be advised to use caution when driving or operating machinery until they are certain 
that talimogene laherparepvec does not adversely affect them. 
 
4.8 Undesirable effects 
 
Summary of safety profile 
 
The safety of Imlygic was evaluated in the pivotal study where 292 patients received at least 1 dose of 
Imlygic (see section 5.1). The median duration of exposure to Imlygic was 23 weeks (5.3 months). 
Twenty six (26) patients were exposed to Imlygic for at least one year. 
 
The most commonly reported adverse reactions (≥ 25%) in Imlygic-treated patients were fatigue 
(50.3%), chills (48.6%), pyrexia (42.8%), nausea (35.6%), influenza-like illness (30.5%), and injection 
site pain (27.7%). Overall, ninety eight per cent (98%) of these adverse reactions reported were mild 
or moderate in severity. The most common grade 3 or higher adverse reaction was cellulitis (2.1%) 
(see section 4.4). 
 
Tabulated list of adverse reactions 
 
Adverse reactions were determined based on clinical trials in patients with melanoma treated with 
Imlygic compared to GM-CSF and post-marketing experience. Incidence of adverse reactions are 
presented by system organ class and by frequency. Frequencies are defined as: very common (≥ 1/10), 
common (≥ 1/100 to < 1/10) and uncommon (≥ 1/1,000 to < 1/100). Within each frequency grouping, 
adverse reactions are presented in order of decreasing seriousness. 
 



 

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Table 3. Adverse reactions from clinical trials in patients with melanoma and post-marketing 
experience 
 
Infections and infestations 
Common Cellulitis*, Oral herpes
Uncommon Incision site infection
Neoplasms benign, malignant and unspecified (including cysts and polyps) 
Common  Tumour pain, Infected neoplasm
Uncommon Plasmacytoma at injection site*
Blood and lymphatic system disorders
Very common Oedema peripheral
Common  Anaemia 
Immune system disorders 
Common Immune-mediated events†*
Uncommon Hypersensitivity 
Metabolism and nutrition disorders 
Common  Dehydration 
Nervous system disorders 
Very common Headache 
Common Confusional state, Anxiety, Depression, Dizziness, Insomnia 
Eye disorders 
Uncommon Keratitis herpetic 
Ear and labyrinth disorders 
Common Ear pain 
Cardiac disorders 
Common Tachycardia 
Vascular disorders 
Common  Deep vein thrombosis, Hypertension, Flushing
Respiratory, thoracic and mediastinal disorders
Very common Cough 
Common  Dyspnoea, Oropharyngeal pain, Upper respiratory tract infection 
Uncommon Obstructive airways disorder 
Gastrointestinal disorders 
Very common  Vomiting, Diarrhoea, Constipation, Nausea
Common  Abdominal pain, Abdominal discomfort
Skin and subcutaneous tissue disorders
Common  Vitiligo, Rash, Dermatitis
Uncommon Granulomatous dermatitis
Musculoskeletal and connective tissue disorders
Very common Myalgia, Arthralgia, Pain in extremity
Common Back pain, Groin pain
General disorders and administration site conditions
Very common  Influenza like illness*, Pyrexia, Chills, Fatigue, Pain, Injection site reactions§
Common  Malaise, Axillary pain
Investigations 
Common  Weight decreased 
Injury, poisoning and procedural complications
Common Wound complication, Wound secretion, Contusion, Procedural pain 

§ Injection site reactions include: very common term of injection site pain, common terms of injection site 
erythema, injection site haemorrhage, injection site swelling, injection site reaction, injection site inflammation, 
secretion discharge, injection site discharge, uncommon term of injection site warmth. 
† Immune mediated events include: uncommon terms of vasculitis, pneumonitis, worsening psoriasis and 
glomerulonephritis. 
* See description of selected adverse reactions 
 



 

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Description of selected adverse reactions 
 
Immune-mediated events 
 
Immune-mediated events reported in the pivotal clinical study included a case of worsening psoriasis 
in a patient with a prior history of psoriasis, one case of pneumonitis in a patient with a prior history of 
autoimmune disease, one case of vasculitis, and two cases of glomerulonephritis of which one 
presented with acute renal failure. 
 
Plasmacytoma 
 
In clinical trials, one case of plasmacytoma at injection site was observed in a patient who was found 
to have multiple myeloma. 
 
Cellulitis 
 
In the pivotal clinical trial (study 005/05), events of cellulitis were recorded, some of them being 
considered as serious adverse events. However, none lead to permanent discontinuation of Imlygic 
treatment. Careful wound care and infection precautions are recommended, particularly if tissue 
necrosis results in open wounds. 
 
Influenza-like symptoms 
 
90% of patients treated with Imlygic experienced influenza-like symptoms. Pyrexia, chills, and 
influenza like illness, which can occur any time during Imlygic treatment, generally resolved within 
72 hours. These events were reported more frequently within the period of the first 6 treatments, 
particularly in patients who were HSV-1 negative at baseline. 
 
Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
There is no clinical experience with overdose with Imlygic. Doses up to 4 mL at a concentration of 
108 PFU/mL every 2 weeks have been administered in clinical trials with no evidence of dose limiting 
toxicity. The maximum dose of Imlygic that can be safely administered has not been determined. In 
the event of a suspected overdose or inadvertent intravenous administration, the patient should be 
treated symptomatically, e.g. with acyclovir or other anti-viral agents (see section 4.4) and supportive 
measures instituted as required. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antineoplastic and immunomodulating agents, ATC code: L01XX51. 
 
Mechanism of action 
 
Talimogene laherparepvec is an oncolytic immunotherapy that is derived from HSV-1. Talimogene 
laherparepvec has been modified to replicate within tumours and to produce the immune stimulatory 
protein human GM-CSF. Talimogene laherparepvec causes the death of tumour cells and the release 
of tumour-derived antigens. It is thought that together with GM-CSF, it will promote a systemic anti-



 

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tumour immune response and an effector T-cell response. Mice that had complete regression of their 
primary tumours following treatment were resistant to subsequent tumour rechallenge. 
 
The modifications to talimogene laherparepvec from HSV-1 include deletion of ICP34.5 and ICP47. 
Whereas anti-viral immune responses defend normal cells following infection by talimogene 
laherparepvec, tumours have been shown to be susceptible to injury and cell death from ICP34.5-
deficient HSV-1 viruses, including talimogene laherparepvec. Deletion of ICP47 prevents down-
regulation of antigen presentation molecules and increases the expression of HSV US11 gene, thereby 
enhancing viral replication in tumour cells. 
 
Clinical efficacy and safety 
 
Study 005/05 
 
The safety and efficacy of Imlygic monotherapy compared with subcutaneously administered 
GM-CSF were evaluated in a phase 3, multinational, open-label, and randomised clinical study of 
patients with stage IIIB, IIIC, and IV melanoma that was not considered to be surgically resectable. 
Previous systemic treatment for melanoma was allowed but not required. Patients with active brain 
metastases, bone metastases, extensive visceral disease, primary ocular or mucosal melanoma, 
evidence of immunosuppression, or receiving treatment with a systemic anti-herpetic agent were 
excluded from the study. 
 
Patients were randomised in a 2:1 ratio to receive either Imlygic or GM-CSF (N = 436; 295 Imlygic, 
141 GM-CSF). Imlygic was administered by intralesional injection at an initial concentration of 
106 (1 million) PFU/mL on day 1, followed by a concentration of 108 (100 million) PFU/mL on day 21 
and every 2 weeks thereafter at a dose of up to 4 mL. GM-CSF was administered subcutaneously at 
125 µg/m2 delivered daily for 14 days followed by a 14-day rest period in repeating intervals. 
 
To allow for delayed immune-mediated anti-tumour effects to occur, patients were treated for a 
minimum of 6 months or until there were no longer any injectable lesions. During this period, 
treatment was to continue despite an increase in size in existing lesion(s) and/or development of new 
lesion(s) unless the patient developed intolerable toxicity or the investigator believed that it was in the 
best interest of the patient to stop treatment or to be given other therapy for melanoma. After 6 months 
of treatment, patients were to continue treatment until clinically relevant disease progression (i.e. 
disease progression associated with a decline in performance status and/or alternative therapy was 
required in the opinion of the investigator). Patients experiencing a response at 12 months of treatment 
could continue treatment for up to an additional 6 months. The mean (SD) treatment duration for the 
intent-to-treat (ITT) population was 15.76 weeks (15.79) in the GM-CSF arm and 26.83 weeks (18.39) 
in the Imlygic arm. The primary endpoint was durable response rate (DRR) [defined as the percent of 
patients with complete response (CR) or partial response (PR) maintained continuously for a minimum 
of 6 months] per blinded central review. The secondary endpoints included overall survival (OS), 
overall response rate (ORR) [PR+CR], time to response, duration of response, and time to treatment 
failure (time from randomisation until the first episode of clinically relevant disease progression where 
there is no response achieved after the progression event, or until death). 
 
The mean age was 63 (range: 22 to 94) years; 26.5% were over 65 years old and 23.3% were over 
74 years old. The majority of patients, 98%, were caucasian. Male patients comprised 57% of study 
population and 70% of patients were baseline ECOG 0 performance status. Of the enrolled patients, 
22% had stage IV M1c disease and 53% of patients had received prior therapy for melanoma such as 
chemotherapy and cytokine-based immunotherapy in addition to surgery, adjuvant therapy or 
radiation. Overall, 58% of all patients enrolled into the study were seropositive for wild-type HSV-1 at 
baseline and 32.6% were seronegative; the HSV-1 serostatus of the remaining 9.4% was unknown. 
 
The difference in DRR between Imlygic and GM-CSF in the ITT population was statistically 
significant (see table 4) in favour of Imlygic. 
 



 

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Table 4. Summary of results for the ITT population from Imlygic study 005/05 
 
 Study 

endpoint 
Imlygic N = 295 GM-CSF N = 141 

Durable response rate  
 

Primary 16.3% (n = 48) 
(95% CI: 12.1, 20.5) 

2.1% (n = 3) 
(95% CI: 0.0, 4.5) 

Odds ratio 8.9; (95% CI: 2.7, 29.2) 
P < 0.0001

Overall response rate  
(% CR, % PR) 

Secondary 26.4% (n = 78) 
(95% CI: 21.4%, 31.5%)  
(10.8% CR, 15.6% PR)

5.7% (n = 8) 
(95% CI: 1.9%, 9.5%) 
(0.7% CR, 5% PR) 

Overall survival Secondary Median 23.3 (95% CI: 
19.5, 29.6) months

Median 18.9 (95% CI: 16.0, 
23.7) months 

HR: 0.79; (95% CI: 0.62, 1.00) p = 0.051 
Duration of response  
(ongoing response at 
last tumour 
evaluation) 

Secondary Not reached 
(Range: > 0.0 to 
> 16.8 months)

Median 2.8 months 
(Range: 1.2 to 
> 14.9 months) 

HR: 0.46; (95% CI: 0.35, 0.60) 
Time to response 
(median) 

Secondary 4.1 months 3.7 months 

Time to treatment 
failure (median) 

Secondary 8.2 months 
(95% CI: 6.5, 9.9)

2.9 months  
(95% CI: 2.8, 4.0) 

HR: 0.42; (95% CI: 0.32, 0.54) 
 
Among the Imlygic-treated responders, 56 (72%) responses were still ongoing at the time of primary 
analysis. Of the responders, 42 (54%) experienced a ≥ 25% increase in overall size of existing 
lesion(s) and/or developed a new lesion(s) prior to ultimately achieving a response. 
 
In an analysis to evaluate systemic activity of Imlygic, 27 of 79 patients (34.2%) had a ≥ 50% overall 
decrease in non-visceral lesions that were not injected with Imlygic, and 8 of 71 patients (11.3%) had 
a ≥ 50% overall decrease in visceral lesions that were not injected with Imlygic. 
 
Figure 4. Kaplan-Meier plot –overall survival (ITT population) 
 

 
Censor indicated by Vertical Bar I. 

Imlygic 
GM-CSF 

Imlygic 295 269 230 187 159 145 125 95 66 36 16 2 0 
GM-CSF 141 124 100 83 63 52 46 36 27 15 5 0 0 

Median [95% CI] 23.3 [19.5, 29.6] months 
Median [95% CI] 18.9 [16.0, 23.7] months 

Log-rank p-value = 0.0511 
Hazard Ratio [95% CI] = 0.79 [0.62, 1.00] 

0 5 10 15 20 25 30 35 40 45 50 55 60 

100% 

90% 

80% 

70% 

60% 

50% 

40% 

30% 

20% 

10% 

0% 
 

Number of Patients at Risk 

Pr
op

or
tio

n A
liv

e 

GRH0116v1

Months 



 

14 

 
No overall differences in safety or efficacy were observed between elderly (≥ 65 years old) and 
younger adult patients. 
 
Exploratory subgroups 
 
Exploratory subgroup analyses for DRR and overall survival by stage of disease were also carried out 
(see figure 5 and table 5). While the pivotal study was not powered to evaluate efficacy in these 
individual subgroups, patients with no visceral disease derived greater benefit from Imlygic treatment 
than those with more advanced disease. 
 
Table 5. Summary of results from exploratory subgroup analysis from Imlygic study 005/05 
 

 DRR, (%) ORR, (%) OS (hazard ratio) 

Imlygic GM-CSF Imlygic GM-CSF Imlygic vs GM-CSF 

Stage§ IIIB/IIIC/ stage 
IVM1a  
(Imlygic, n = 163; 
GM-CSF, n = 86) 

25.2 1.2 40.5 2.3 0.57, (95% CI: 0.40, 
0.80); 

Stage§ IVM1B/ IVM1C
(Imlygic, n = 131; 
GM-CSF, n = 55) 

5.3 3.6 9.2 10.9 1.07, (95% CI: 0.75, 
1.52); 

§ American Joint Committee on Cancer (AJCC) staging 6th edition. 
 



 

15 

Figure 5. Kaplan-Meier estimate of overall survival by randomised treatment arm for disease 
stage IIIB/IIIC/ stage IVM1a (exploratory subgroup analysis) 
 

 
Censor indicated by vertical bar ׀ 
NE = not estimable 
 
Due to the exploratory nature of the analysis and based on the current evidence, it has not been 
established that Imlygic is associated with an effect on overall survival. 
 
Paediatric population 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
Imlygic in one or more subsets of the paediatric population in melanoma (see section 4.2 for 
information on paediatric use). 
 
5.2 Pharmacokinetic properties 
 
Talimogene laherparepvec is a genetically modified and replication-competent HSV-1 virus. 
Therefore, its pharmacokinetics and biodistribution are driven by the site of intralesional injection, 
tumour-selective replication, and release from tumour tissue. 
 
Absorption 
 
Cellular uptake of talimogene laherparepvec occurs through HSV-1 receptors on tumours and non-
tumour cells following local injection into tumours. As talimogene laherparepvec is injected and 
replicates intratumourally, bioavailability and systemic concentration of talimogene laherparepvec are 
not predictive of drug substance activity and therefore have not been evaluated. 
 
Metabolism/elimination 
 
Talimogene laherparepvec is cleared through general host-defence mechanisms (e.g. autophagy, 
adaptive immune responses). Talimogene laherparepvec is degraded by typical endogenous protein 

0 5 10 15 20 25 30 35 40 45 50 55 60 
 

100% 

80% 

60% 

40% 

20% 

0% 
 

Ka
pla

n-
Me

ier
 P

er
ce

nt 
Al

ive
 

Number of Subjects at Risk: 

1: GM-CSF (N = 86) Median (95% CI) 21.5 (17.4, 29.6) months 
2: Talimogene Laherparepvec (N = 163) Median (95% CI) 41.1 (30.6, NE) months 

86 78 65 55 43 35 30 22 17 10 2 0  
163 157 146 129 113 104 93 73 51 23 10 1 0 

 

1: 
2: 

 

Study Month 

GRH0149v1



 

16 

and DNA catabolic pathways. As with other wild-type HSV-1 infections, a latent pool of talimogene 
laherparepvec DNA may persist in neuronal cell bodies innervating the injection sites; therefore, the 
occurrence of latent infection with talimogene laherparepvec cannot be excluded. 
 
Biodistribution (within the body) and viral shedding (excretion/secretion) 
 
Talimogene laherparepvec DNA was quantified with a highly sensitive and specific quantitative 
Polymerase Chain Reaction (qPCR) assay which may not correlate with viral infectivity risk. 
Talimogene laherparepvec was also quantified in selected patient samples in clinical studies using 
viral infectivity assays at the injection sites and in some cases of potential herpetic lesions. 
 
Clinical biodistribution, elimination, and shedding 
 
The biodistribution and shedding of intralesionally administered talimogene laherparepvec were 
investigated in a clinical study that measured talimogene laherparepvec DNA in blood, urine, injection 
site, exterior of the occlusive dressings, oral mucosa, anogenital area, and suspected herpetic lesions. 
Sixty patients with melanoma received Imlygic intralesional injection at a dose and schedule same as 
clinical study 005/05 (see section 5.1). Occlusive dressings samples were collected during treatment. 
Blood and urine samples were collected during treatment and for up to 30 days after the end of 
treatment. Injection site, oral mucosa, and anogenital area samples were collected during treatment and 
for up to 60 days after the end of treatment. Suspected herpetic lesion samples were collected any time 
a patient experienced lesions of suspected herpetic origin. If the qPCR testing for talimogene 
laherparepvec DNA was positive, then a TCID50 assay was performed to measure viral infectivity. In 
the 60 patients treated, data indicate that talimogene laherparepvec DNA was present in all sites during 
the study (see table 6). 
 
Table 6. Patients with detectable DNA during treatment 

 
Body fluid/site Patients with detectable DNA during 

treatment (n = 60) 
Blood 59 (98%)
Urine 19 (32%)
Injection site 60 (100%)
Exterior of the occlusive dressing 48 (80%)
Oral mucosa 8 (13%)
Anogenital area 5 (19%)a

aFor the anogenital area, 26 patients were tested for Imlygic DNA. 
 
The proportion of samples and subjects with talimogene laherparepvec DNA was highest during cycle 
2 of treatment for the blood, urine, injection site, and occlusive dressings; highest in cycle 1 of 
treatment for the oral mucosa; and highest in cycles 1 and 2 for the anogenital area. Among patients 
with detectable talimogene laherparepvec DNA in the blood, urine, oral mucosa, and anogenital area, 
no samples had detectable talimogene laherparepvec DNA 30 days after the end of treatment. For 
patients with detectable DNA in injected lesions, no samples had detectable talimogene laherparepvec 
DNA 60 days after end of treatment. 
 
Overall 3 of 19 patients with lesions of suspected herpetic origin had talimogene laherparepvec DNA 
present at any time during the study. Viral activity was measured in samples that were positive for 
talimogene laherparepvec DNA from the injection site, occlusive dressings, oral mucosa, anogenital 
area, and suspected herpetic lesions. No viral activity was detected in samples of the occlusive 
dressings, oral mucosa, anogenital area, and suspected herpetic lesions. Infectious talimogene 
laherparepvec virus was detected at the site of injection in 7 (11%) patients at multiple time points in 
the study; no samples were positive for viral infectivity after cycle 2 or after the end of treatment. 
 



 

17 

Pharmacokinetics in special populations 
 
No pharmacokinetic studies using talimogene laherparepvec have been conducted in special 
populations. 
 
5.3 Preclinical safety data 
 
At doses up to 4 x 108 PFU/kg or 107 PFU/dose (60-fold over the highest proposed clinical dose), 
single or repeated doses of talimogene laherparepvec administered by SC, IV, or intratumoural 
injection were well tolerated in immunocompetent mice, rats, and dogs. No neuropathology or adverse 
neurological effects were observed. In an in vivo study of intracerebral injection, talimogene 
laherparepvec was 10,000-fold less neurovirulent as compared to the wild-type HSV-1 dose that 
results in death 50% of the time in mice. 
 
Talimogene laherparepvec was injected into various xenograft tumours at doses up to 2 x 108 PFU/kg 
(30-fold over the highest proposed clinical dose) in immunodeficient mice (nude and SCID). Lethal 
systemic viral infection was observed in up to 20% of nude mice (primarily deficient in T lymphocyte 
function) and 100% of SCID mice (devoid of both T and B lymphocytes). 
 
Across studies, fatal disseminated viral infection was observed in 14% of nude mice following 
treatment with talimogene laherparepvec at doses that are 10 to 100-fold higher than those that result 
in 100% lethality with wild-type HSV-1. 
 
Mutagenicity 
 
The genotoxic potential of talimogene laherparepvec has not been evaluated in long-term animal or 
human studies. Because wild-type HSV-1 does not integrate into the host genome, the risk of 
insertional mutagenesis with talimogene laherparepvec is negligible. 
 
Carcinogenicity 
 
The carcinogenic potential of talimogene laherparepvec has not been evaluated in long-term animal or 
human studies. However, available data for talimogene laherparepvec and wild-type HSV-1 do not 
indicate a carcinogenic risk in humans. 
 
Reproductive and development toxicity 
 
There were no impacts to male or female reproductive tissues following treatment of adult mice at 
doses up to 4 x 108 PFU/kg (60-fold higher, on a PFU/kg basis, compared to the maximum clinical 
dose). No effects on embryo-foetal development were observed when talimogene laherparepvec was 
administered during organogenesis to pregnant mice at doses up to 4 x 108 (400 million) PFU/kg 
(60-fold higher, on a PFU/kg basis, compared to the maximum clinical dose). Negligible amounts 
(< 0.001% of maternal blood levels) of talimogene laherparepvec DNA were found in foetal blood. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Di-sodium phosphate dihydrate 
Sodium dihydrogen phosphate dihydrate 
Sodium chloride 
Myo-inositol 
Sorbitol (E420) 
Water for injections 
 



 

18 

6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products. 
 
6.3 Shelf life 
 
Unopened vial 
 
5 years. 
 
Thawing Imlygic vials 
 
 Before use, thaw frozen Imlygic vials at room temperature (20°C to 25°C) until Imlygic is 

liquid (approximately 30 minutes). Gently swirl. Do NOT shake. 
 Vials should be thawed and stored in the original carton until administration in order to protect 

from light. 
 
After thawing 
 
 After thawing, administer Imlygic as soon as practically feasible. 
 Thawed Imlygic is stable when stored at temperatures of 2°C up to 25°C protected from light in 

its original vial, in a syringe, or in the original vial followed by a syringe. Do not exceed the 
storage times specified in table 7 and table 8. 

 If storing thawed Imlygic in the original vial followed by a syringe: 
o the same temperature range should be maintained throughout the duration of storage until 

administration. 
o the storage time in the syringe at ambient temperature up to 25°C cannot exceed 2 hours 

for 106 (1 million) PFU/mL and 4 hours for 108 (100 million) PFU/mL (see table 7). 
o the maximum cumulative storage time (storage time in vial plus storage time in syringe) 

cannot exceed the durations in table 8. 
 Imlygic must not be refrozen once it has thawed. Discard any thawed Imlygic in the vial or 

syringe stored longer than the specified times below. 
 
Table 7. Maximum storage time for thawed Imlygic in syringe 
 

 106 (1 million) PFU/mL 108 (100 million) PFU/mL 
2°C to 8°C  8 hours 8 hours 
up to 25°C 2 hours 4 hours 

 
Table 8. Maximum cumulative storage time (storage time in vial plus storage time in syringe) for 
thawed Imlygic 
 

 106 (1 million) PFU/mL 108 (100 million) PFU/mL 
2°C to 8°C  24 hours 1 week (7 days) 
up to 25°C 12 hours 24 hours 

 
6.4 Special precautions for storage 
 
Store and transport frozen (-90°C to -70°C). 
Store in the original carton in order to protect from light. 
 



 

19 

6.5 Nature and contents of container 
 
Imlygic is provided as a one ml preservative-free solution in a single–use vial (cyclic olefin polymer 
plastic resin) with stopper (chlorobutyl elastomer) and seal (aluminium) with flip-off cap 
(polypropylene) in two different presentations: 
 
Figure 6. Single-use vial permanently inserted into a clear copolyester plastic sleeve 

 

OR 
 
Figure 7. Single-use vial without a clear plastic sleeve 

 
 

 
The vial cap is colour coded: 106 (1 million) PFU/mL is light green and 108 (100 million) PFU/mL is 
royal blue. 
 
6.6 Special precautions for disposal and other handling 
 
Follow local institutional guidelines for handling and administration, personal protective equipment, 
accidental spills, and waste disposal. 
 Wear protective gown or laboratory coat, safety glasses, or face shield and gloves while 

preparing or administering Imlygic. Cover any exposed wounds before administering. Avoid 
contact with skin, eyes or mucous membranes. 

 After administration, change gloves prior to applying occlusive dressings to injected lesions. 
Wipe the exterior of occlusive dressing with an alcohol wipe. It is recommended to keep 
injection sites covered with airtight and watertight dressings at all times, if possible. To 
minimise the risk of viral transmission, patients should keep their injection site covered for at 
least 8 days from the last treatment or longer if the injection site is weeping or oozing. Advise 
patients to apply dressing as instructed by the healthcare professional and to replace the dressing 
if it falls off. 

 Dispose of all materials that have come in contact with Imlygic (e.g. vial, syringe, needle, any 
cotton or gauze) in accordance with local institutional procedures. 

 
Accidental exposure 
 In the event of an accidental occupational exposure to Imlygic (e.g. through a splash to the eyes 

or mucous membranes) during preparation or administration, flush with clean water for at least 
15 minutes. In the event of exposure to broken skin or needle stick, clean the affected area 
thoroughly with soap and water and/or disinfectant. 

 Treat all Imlygic spills with a virucidal agent and absorbent materials. 



 

20 

 Advise patients to place used dressings and cleaning materials in a sealed plastic bag as they 
may be potentially contaminated, and to dispose of the bag in household waste. 

 
This medicine contains genetically modified organisms. Unused medicine must be disposed of in 
compliance with the institutional guidelines for genetically modified organisms or biohazardous waste, 
as appropriate. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Amgen Europe B.V. 
Minervum 7061 
NL-4817 ZK Breda 
The Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/15/1064/001 
EU/1/15/1064/002 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 16 December 2015 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 



 

21 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 
MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE 

 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 



 

22 

A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 
MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE 

 
Name and address of the manufacturer of the biological active substance 
BioVex Inc. - Subsidiary of Amgen, Inc. 
34 Commerce Way 
Woburn 
Massachusetts 
01801 
United States 
 
Name and address of the manufacturers responsible for batch release 
Amgen Europe B.V. 
Minervum 7061 
4817 ZK Breda 
Netherlands 
 
Amgen NV 
Telecomlaan 5-7 
1831 Diegem 
Belgium 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
 Periodic safety update reports 
 
The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal. 
 
The marketing authorisation holder shall submit the first periodic safety update report for this product 
within 6 months following authorisation. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
 Risk Management Plan (RMP) 
 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent 
updates of the RMP. 
 
An updated RMP should be submitted: 
 At the request of the European Medicines Agency; 
 Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 

 



 

23 

 Additional risk minimisation measures 
 
Prior to launch of IMLYGIC in each Member State the Marketing Authorisation Holder (MAH) must 
agree about the content and format of the educational and controlled distribution programme, 
including communication media, distribution modalities, and any other aspects of the programme, 
with the National Competent Authority. 
 
The educational programme is aimed to inform about important risks associated with IMLYGIC: 
 Herpetic infection occurring throughout the entire body (disseminated herpetic infection) in 

immunocompromised individuals (those with any congenital or acquired cellular and/or 
humoral immune deficiency, i.e. HIV/AIDS, leukaemia, lymphoma, common variable 
immunodeficiency, or those who require high-dose steroids or other immunosuppressive agents) 

 Accidental exposure of Healthcare Professionals (HCPs) to IMLYGIC 
 Spread of IMLYGIC to close contacts or healthcare providers after direct contact with injected 

lesions or body fluids 
 Symptomatic herpetic infection due to latency and reactivation of IMLYGIC or herpes (wild-

type HSV-1) in patients 
 Patients with a weakened immune system (immunocompromised patients) treated with 

IMLYGIC and suffering from concomitant infection 
 Combination with other therapies like chemotherapy or immunosuppressive agents 
 Pregnant and lactating women 
 
The MAH shall ensure that in each Member State where IMLYGIC is marketed, all healthcare 
professionals and patients/carers who are expected to prescribe, dispense and use IMLYGIC have 
access to/are provided with the following educational package: 
 Physician educational material 
 Patient information pack 
 
The physician educational material should contain: 
 The Summary of Product Characteristics 
 Guide for healthcare professionals 
 Patient alert card 
 
 Guide for healthcare professionals shall contain the following key elements: 

o Information on the risk of herpetic infection in patients treated by IMLYGIC 
o Information on the risk of disseminated herpetic infection in immunocompromised 

individuals treated by IMLYGIC 
o Recommendation regarding accidental exposure of IMLYGIC to HCPs: 
o To always wear protective gown/laboratory coat, safety glasses and gloves while 

preparing or administrating IMLYGIC; 
o To avoid contact with skin, eyes, mucous membranes and ungloved direct contact with 

injected lesions or body fluids of treated patients; 
o Instruction on first aid after accidental exposure; 
o Immunocompromised and pregnant healthcare professionals should not prepare and 

administer IMLYGIC. 
o Recommendation regarding the accidental transmission of IMLYGIC from patient to 

close contacts or HCPs: 
o Instruction on how to behave after administration/accidental transmission and how and 

how often the dressing has to be changed and who should not change the dressing; 
o Instructions to minimise the risk of exposure of blood and body fluids to close contacts 

for the duration of IMLYGIC treatment through 30 days after the last administration of 
IMLYGIC. The following activities should be avoided: 
 Sexual intercourse without a latex condom 
 Kissing if either party has an open mouth sore 
 Common usage of cutlery, crockery, and drinking vessels 
 Common usage of injection needles, razorblades and toothbrushes; 



 

24 

o Adequate waste disposal and decontamination, following the recommendations for 
disposal of biohazardous waste. 

o Information on IMLYGIC use in pregnancy 
o Instructions how to handle possible adverse events including providing of batch number 

when reporting adverse drug reactions 
 
 The patient alert card shall contain the following key messages: 

o A warning message for HCPs treating the patient at any time, including in conditions of 
emergency, that the patient is using IMLYGIC 

o Contact details of the IMLYGIC prescriber 
o Details about IMLYGIC treatment start date, batch number, date administered, product 

manufacturer and license holder 
o Information of herpetic lesions 

 
 The patient information pack should contain: 

o Patient information leaflet 
o A patient/carer and close contacts guide 

 
 The Patient/carer and close contacts guide shall contain the following key messages: 

o A description of the important risks associated with the use of IMLYGIC; 
o Instruction on how to behave after administration and how and how often the dressing has 

to be changed and who should not change the dressing. 
o Information of the sign and symptoms of the risk of herpetic infection; 
o Information on IMLYGIC use in pregnancy; 
o Recommendation regarding the accidental transmission of IMLYGIC from patient to 

close contacts or HCPs: 
o Instructions to minimise the risk of exposure of blood and body fluids to close contacts 

for the duration of IMLYGIC treatment through 30 days after the last administration of 
IMLYGIC. The following activities should be avoided: 
 Sexual intercourse without a latex condom 
 Kissing if either party has an open mouth sore 
 Common usage of cutlery, crockery, and drinking vessels 
 Common usage of injection needles, razorblades and toothbrushes; 

o Adequate waste disposal and decontamination, following the recommendations for 
disposal of biohazardous waste. 

o Instruction on how to behave after accidental transmission. 
 
The controlled distribution programme is aimed to manage the product supply chain to ensure that 
cold storage requirements are observed and to control the distribution of IMLYGIC to qualified 
centres and up to the patients. 
 
The MAH shall ensure that in each Member State where IMLYGIC is marketed, a system aimed to 
control distribution to IMLYGIC beyond the level of control ensured by routine risk minimisation 
measures. The following requirements need to be fulfilled before the product is dispensed: 
 Adequately trained and experienced HCPs in order to minimise the risk of occurrence of 

specified adverse drug reactions in patients, HCPs, and close contacts of the patients; 
 Trained HCPs and support personnel regarding safe and appropriate storage, handling, and 

administration of IMLYGIC, and clinical follow-up for patients treated with IMLYGIC; 
 Provide specified safety information to patients and communicate to patients the importance for 

sharing this information with family and caregivers; 
 Trained HCPs to record batch number information in patient´s charts and on the patient´s alert 

card for all injections and to provide the batch number when reporting adverse drug reactions. 
 



 

25 

 Obligation to conduct post-authorisation measures 
 
The MAH shall complete, within the stated timeframe, the below measures: 
 

Description Due date 
To submit the preliminary results from Study 20110266 (a phase 2, multicentre, 
randomised, open-label trial assessing the efficacy and safety of talimogene 
laherparepvec neoadjuvant treatment plus surgery vs surgery alone for resectable 
stage IIIB to IVM1a melanoma) 
 

31th December, 
2019 

To provide preliminary efficacy results from the phase III part of the 
Study 20110265 (a multicentre trial evaluating the combination of talimogene 
laherparepvec with pembrolizumab) 
 

30th June, 2021 

 



 

26 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



 

27 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



 

28 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Imlygic 106 plaque forming units (PFU)/mL solution for injection 
talimogene laherparepvec 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each vial contains 1 mL of 1 x 106 (1 million) plaque forming units (PFU) of talimogene 
laherparepvec. 
 
 
3. LIST OF EXCIPIENTS 
 
Di-sodium phosphate dihydrate, sodium dihydrogen phosphate dihydrate, sodium chloride, 
myo-inositol, sorbitol (E420), water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
1 vial. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Intralesional use. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store and transport frozen at -90° to -70°C. 
 
 



 

29 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
This medicine contains genetically modified organisms. 
Unused medicine must be disposed of in compliance with the institutional guidelines for genetically 
modified organisms or biohazardous waste. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Amgen Europe B.V. 
Minervum 7061 
NL-4817 ZK Breda 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/15/1064/001 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



 

30 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Imlygic 106 PFU/mL injection 
talimogene laherparepvec 
Intralesional use 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1 mL 
 
 
6. OTHER 
 
 



 

31 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Imlygic 108 plaque forming units (PFU)/mL solution for injection 
talimogene laherparepvec 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each vial contains 1 mL of 1 x 108 (100 million) plaque forming units (PFU) of talimogene 
laherparepvec. 
 
 
3. LIST OF EXCIPIENTS 
 
Di-sodium phosphate dihydrate, sodium dihydrogen phosphate dihydrate, sodium chloride, 
myo-inositol, sorbitol (E420), water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
1 vial. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Intralesional use. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store and transport frozen at -90° to -70°C. 
 
 



 

32 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
This medicine contains genetically modified organisms. 
Unused medicine must be disposed of in compliance with the institutional guidelines for genetically 
modified organisms or biohazardous waste. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Amgen Europe B.V. 
Minervum 7061 
NL-4817 ZK Breda 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/15/1064/002 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 



 

33 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Imlygic 108 PFU/mL injection 
talimogene laherparepvec 
Intralesional use 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1 mL 
 
 
6. OTHER 
 
 
 
 



 

34 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
B. PACKAGE LEAFLET 



 

35 

Package leaflet: Information for the patient 
 

Imlygic 106 plaque forming units (PFU)/mL solution for injection 
Imlygic 108 plaque forming units (PFU)/mL solution for injection 

talimogene laherparepvec 
 
 

This medicine is subject to additional monitoring. This will allow quick identification of new safety 
information. You can help by reporting any side effects you may get. See the end of section 4 for how 
to report side effects. 
 
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 healthcare professional (doctor or nurse). 
- If you get any side effects, talk to your healthcare professional. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
 
What is in this leaflet 
 
1. What Imlygic is and what it is used for 
2. What you need to know before and during Imlygic treatment 
3. How Imlygic is given 
4. Possible side effects 
5. How Imlygic is stored 
6. Contents of the pack and other information 
 
 
1. What Imlygic is and what it is used for 
 
Imlygic is used to treat adult patients with a type of skin cancer called melanoma that has spread in the 
skin or to the lymph nodes, when surgery is not an option. 
 
The active ingredient of Imlygic is talimogene laherparepvec. This is a weakened form of herpes 
simplex virus type-1 (HSV-1), which is commonly called the cold sore virus. To get Imlygic from 
HSV-1, the virus has been changed so that it multiplies more effectively in tumours than in normal 
cells. This leads to destruction of infected tumour cells. Imlygic also works by helping your immune 
system to recognise and destroy tumours throughout your body. 
 
 
2. What you need to know before and during Imlygic treatment 
 
You will not be given Imlygic: 
- if you are allergic to talimogene laherparepvec or any of the other ingredients of this medicine 

(listed in section 6). 
- if your healthcare professional has told you that you have a severely weakened immune system. 
 
Warnings and precautions 
 
Talk to your healthcare professional before being given Imlygic. 
 
Patients with weakened immune systems 
 
Life-threatening herpes infection may occur in patients with weakened immune systems. Tell your 
healthcare professional if you have or have ever had a weakened immune system, if you have 



 

36 

HIV/AIDS, blood or bone marrow cancer, or if you are taking steroids or other medicines that 
suppress your immune system. 
 
Accidental spread of Imlygic to yourself and others 
 
Imlygic can be spread to other parts of your body or to other people through direct contact with your 
body fluids or injection sites. 
 
You should do the following to avoid spreading Imlygic to other areas of your body or to your close 
contacts (close contacts include household members, caregivers, sex partners, or someone you share a 
bed with): 
 Avoid direct contact between your injection sites or body fluids (e.g. blood and urine) and close 

contacts (e.g. use latex condoms when engaging in sexual activity, avoid kissing close contacts 
if either of you has an open mouth sore) while you are being treated with Imlygic and up to 
30 days after your last dose. 

 Avoid touching or scratching the injection sites. 
 Keep injection sites covered with airtight and watertight dressings at all times. Apply the 

dressing as instructed by your healthcare professional. If the dressing comes loose or falls off, 
replace it immediately with a clean dressing. 

 Place all used dressings and cleaning materials in a sealed plastic bag and throw them away in 
your household waste. 

 
You should tell your close contacts to: 
 Avoid direct contact with your body fluids or injection sites. 
 Wear gloves while changing your dressing. 
 
If your close contacts are accidentally exposed to Imlygic, they should clean the affected area on their 
body with soap and water and/or a disinfectant. If they develop signs or symptoms of herpes infection, 
you should ask them to contact their healthcare professional. If herpetic lesions (blisters or sores) are 
suspected, patients or close contacts have the option of follow-up testing by the Marketing 
Authorisation Holder for further characterisation of the infection. Please discuss with your Healthcare 
Professional. 
 
Close contacts who are pregnant or who have a weakened immune system, and newborns 
 
Ensure that your close contacts who are pregnant or who have a weakened immune system do not 
touch injection sites, used dressings and cleaning materials. Keep used dressings and cleaning 
materials away from newborns. 
 
Herpes infection 
 
Cold sores or a more serious herpes infection may occur during or after treatment with Imlygic. Signs 
and symptoms related to treatment with Imlygic may be the same as for herpes infections, and include 
pain, burning or tingling in a blister around the mouth or genitals, or on the fingers or ears, eye pain, 
light sensitivity, discharge from the eyes, or blurry vision, weakness in arms or legs, extreme 
drowsiness (feeling sleepy), and mental confusion. If you have these signs, you should follow standard 
hygiene practices to prevent viral transmission to others. If herpetic lesions (blisters or sores) are 
suspected, patients or close contacts have the option of follow-up testing by the Marketing 
Authorisation Holder for further characterisation of the infection. Please discuss with your Healthcare 
Professional 
 
Infection and delayed healing at Imlygic injection site 
 
Imlygic may cause infection at the injection site. Signs and symptoms of infection include pain, 
redness, warmth, swelling, discharge or a sore (ulcer), fever, and chills. The injection site may take 
longer to heal than normal. You should tell your healthcare professional if you notice any of these 
symptoms. 



 

37 

 
Autoimmune reactions 
 
Imlygic may cause autoimmune reactions (an over-reaction of the body’s immune system). Some 
people taking Imlygic have developed inflammation in the kidneys (glomerulonephritis), narrowing or 
blockage of blood vessels (vasculitis), swelling of the lungs (pneumonitis), worsening skin scaling 
(psoriasis), and areas of skin without any colour (vitiligo). Inform your healthcare professional if you 
have a history of autoimmune disease. 
 
Plasmacytoma 
 
Imlygic may cause cancerous white blood cells to collect at or near the injection site (plasmacytoma). 
Inform your healthcare professional if you have a history of blood cancer including multiple myeloma. 
 
Difficulty breathing 
 
If you have a tumour in your neck, your healthcare professional may warn you that you might 
experience compression of your airways during treatment with Imlygic. 
 
Patients with no prior herpes infection 
 
If you have never had herpes infection in the past, you may be more likely to get fever, chills, and flu-
like illnesses within the period of the first 6 treatments with Imlygic. 
 
Children and adolescents 
 
Imlygic is not recommended for children and adolescents since the effects of Imlygic in people 
younger than 18 years old are not known. 
 
Other medicines and Imlygic 
 
Tell your healthcare professional if you are taking, have recently taken or might take any other 
medicines, including medicines, such as acyclovir, to treat or prevent herpes infections. Acyclovir and 
other anti-viral treatments may decrease the effects of Imlygic. 
 
Pregnancy and breast-feeding 
 
Ask your healthcare professional for advice if you: 
 think you may be pregnant 
 or are planning to have a baby. 
Your healthcare professional will determine if Imlygic is right for you. 
 
If you are pregnant or breast-feeding, ask your healthcare professional for advice before being given 
this medicine. Imlygic may harm your unborn baby. 
 
Women who are able to become pregnant should use effective contraception to avoid pregnancy 
during treatment with Imlygic. Talk to your healthcare professional about suitable methods of 
contraception. 
 
It is not known whether Imlygic is excreted in breast milk. It is important to tell your healthcare 
professional if you are breast-feeding or plan to do so. They will then help you decide whether to stop 
breast-feeding, or whether to stop taking Imlygic, taking into account the benefit of breast-feeding to 
the baby and the benefit of Imlygic to you. 
 



 

38 

Driving and using machines 
 
When you are being treated with Imlygic you may experience symptoms such as dizziness or 
confusion. This may impair your ability to drive or operate machinery. Use caution when driving or 
operating machinery until you are certain that Imlygic does not adversely affect you. 
 
Imlygic contains sodium and sorbitol 
 
This medicine contains approximately 30 mg sodium (main component of cooking/table salt) in each 
4 mL dose. This is equivalent to 1.5% of the recommended maximum daily dietary intake of sodium 
for an adult. 
 
This medicine contains 80 mg sorbitol in each 4 mL dose. 
 
 
3. How Imlygic is given 
 
Imlygic is given in a healthcare facility under the supervision of a healthcare professional. The initial 
recommended dose is up to 4 mL of Imlygic at a concentration of 106 (1 million) PFU/mL. Subsequent 
doses will be up to 4 mL of Imlygic at a concentration of 108 (100 million) PFU/mL. 
 
Your healthcare professional will inject Imlygic directly into your tumour(s) with a needle and 
syringe. Your second injection will be given 3 weeks after the first injection. After that, you will 
receive injections every 2 weeks for as long as you have the tumour(s). 
 
Your healthcare professional will decide which tumour(s) to inject and may not inject every tumour. 
Your existing tumour(s) may increase in size and new tumour(s) could appear while you are being 
treated with Imlygic. 
 
You can expect to be treated with Imlygic for at least 6 months or longer. 
 
If you miss a dose of Imlygic 
 
It is important for you to keep all your appointments to receive Imlygic. If you miss an appointment, 
ask your healthcare professional when to schedule your next dose. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Infection caused by bacteria (cellulitis) at the injection site has been commonly seen in patients 
receiving Imlygic. Keeping wounds clean and dressed can help prevent these types of infections. 
 
Very commonly, flu-like illnesses, fevers and chills have been seen in patients treated with Imlygic. 
These symptoms generally resolve within the first 72 hours after treatment. 
 
The following side effects have been reported in patients receiving Imlygic: 
 
Very common (may affect more than 1 in 10 people): 
 Tissue swelling (peripheral oedema) 
 Headache 
 Cough 
 Vomiting, diarrhoea, constipation, nausea 
 Muscle pain (myalgia), painful/swollen joints (arthralgia), limb pain 



 

39 

 Flu-like illness, fever (pyrexia), chills, fatigue, pain 
 Pain, redness, bleeding, swelling, inflammation, secretion, discharge, and warmth at the 

injection site 
 
Common (may affect up to 1 in 10 people): 
 Infection caused by bacteria (cellulitis), cold sores (oral herpes) 
 Tumour pain, infected tumour 
 Low red blood cell numbers (anaemia) 
 Side effects related to the immune system such as narrowing or blockage of blood vessels 

(vasculitis), inflammation of the lungs (pneumonitis), worsening scaling of the skin (worsening 
psoriasis), and inflammation of kidneys (glomerulonephritis) 

 Dehydration 
 Confusion, anxiety, depression, dizziness, difficulty sleeping (insomnia) 
 Pain in ear, throat, abdomen, groin, back and underarm 
 Faster heart rate at rest (tachycardia) 
 Blood clot within a deep vein (deep vein thrombosis), high blood pressure (hypertension), 

redness in the face (flushing) 
 Shortness of breath (dyspnoea), upper respiratory infection 
 Abdominal discomfort 
 Areas of skin without any colour (vitiligo), rash, inflamed skin (dermatitis) 
 Generally feeling unwell 
 Weight loss 
 Wound complication, secretion, bruising (contusion), pain after procedure 
 
Uncommon (may affect up to 1 in 100 people): 
 Incision site infection 
 Cancerous white blood cells at or near the injection site (plasmacytoma). 
 Eye infection caused by herpes (keratitis herpetic) 
 Compressed airways (obstructive airways disorder) 
 Allergic reaction (hypersensitivity) 
 
Reporting of side effects 
 
If you get any side effects, talk to your healthcare professional. 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 Imlygic is stored 
 
Imlygic will be stored by the healthcare professionals at your healthcare facility. 
 
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 label and carton after EXP. The 
expiry date refers to the last day of that month. 
 
Store and transport frozen at -90°C to -70°C. 
Store in the original carton in order to protect from light. 
 
 



 

40 

6. Contents of the pack and other information 
 
What Imlygic contains 
 
- The active substance is talimogene laherparepvec. 

Each vial contains 1 extractable mL of solution at a nominal concentration of 1 x 106 (1 million) 
plaque forming units (PFU)/mL or 1 x 108 (100 million) PFU/mL. 

- The other ingredients are di-sodium phosphate dihydrate, sodium dihydrogen phosphate 
dihydrate, sodium chloride, myo-inositol, sorbitol (E420), water for injections (see section 2). 

 
What Imlygic looks like and contents of the pack 
 
Imlygic is a clear to semi-translucent (106 PFU/mL) or semi-translucent to opaque (108 PFU/mL) 
liquid. It is supplied as a 1 mL preservative free solution in a single –use vial (cyclic olefin polymer 
plastic resin) with stopper (chlorobutyl elastomer) and seal (aluminium) with flip-off cap 
(polypropylene). 
 
The vial cap is colour coded: 106 PFU/mL is light green and 108 PFU/mL is royal blue. 
 
Marketing Authorisation Holder and Manufacturer 
Amgen Europe B.V. 
Minervum 7061 
NL-4817 ZK Breda 
The Netherlands 
 
Marketing Authorisation Holder 
Amgen Europe B.V. 
Minervum 7061 
NL-4817 ZK Breda 
The Netherlands 
 
Manufacturer 
Amgen NV 
Telecomlaan 5-7 
1831 Diegem 
Belgium 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
s.a. Amgen n.v. 
Tel/Tél: +32 (0)2 7752711 
 

Lietuva 
Amgen Switzerland AG Vilniaus filialas 
Tel: +370 5 219 7474 
 

България 
Амджен България ЕООД 
Тел.: +359 (0)2 424 7440 
 

Luxembourg/Luxemburg 
s.a. Amgen 
Belgique/Belgien 
Tel/Tél: +32 (0)2 7752711 
 

Česká republika 
Amgen s.r.o. 
Tel: +420 221 773 500 
 

Magyarország 
Amgen Kft. 
Tel.: +36 1 35 44 700 
 



 

41 

Danmark 
Amgen, filial af Amgen AB, Sverige 
Tlf: +45 39617500 
 

Malta 
Amgen B.V. 
The Netherlands 
Tel: +31 (0)76 5732500 
 

Deutschland 
AMGEN GmbH 
Tel.: +49 89 1490960 
 

Nederland 
Amgen B.V. 
Tel: +31 (0)76 5732500 
 

Eesti 
Amgen Switzerland AG Vilniaus filialas 
Tel: +372 586 09553 
 

Norge 
Amgen AB 
Tel: +47 23308000 
 

Ελλάδα 
Amgen Ελλάς Φαρμακευτικά Ε.Π.Ε. 
Τηλ.: +30 210 3447000 
 

Österreich 
Amgen GmbH 
Tel: +43 (0)1 50 217 
 

España 
Amgen S.A. 
Tel: +34 93 600 18 60 
 

Polska 
Amgen Biotechnologia Sp. z o.o. 
Tel.: +48 22 581 3000 
 

France 
Amgen S.A.S. 
Tél: +33 (0)9 69 363 363 
 

Portugal 
Amgen Biofarmacêutica, Lda. 
Tel: +351 21 4220606 
 

Hrvatska 
Amgen d.o.o. 
Tel: +385 (0)1 562 57 20 
 

România 
Amgen România SRL 
Tel: +4021 527 3000 
 

Ireland 
Amgen Ireland Limited 
Tel: +353 1 8527400 
 

Slovenija 
AMGEN zdravila d.o.o. 
Tel: +386 (0)1 585 1767 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
Amgen Slovakia s.r.o. 
Tel: +421 2 321 114 49 
 

Italia 
Amgen S.r.l. 
Tel: +39 02 6241121 
 

Suomi/Finland 
Amgen AB, sivuliike Suomessa/Amgen AB, filial 
i Finland 
Puh/Tel: +358 (0)9 54900500 
 

Kύπρος 
C.A. Papaellinas Ltd 
Τηλ.: +357 22741 741 
 

Sverige 
Amgen AB 
Tel: +46 (0)8 6951100 
 

Latvija 
Amgen Switzerland AG Rīgas filiāle 
Tel: +371 257 25888 
 

United Kingdom 
Amgen Limited 
Tel: +44 (0)1223 420305 
 

 
This leaflet was last revised in 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 



 

42 

 
 
The following information is intended for healthcare professionals only: 
 
Thawing Imlygic vials 
 
 Before use, thaw frozen Imlygic vials at room temperature (20ºC to 25ºC) until Imlygic is liquid 

(approximately 30 minutes). Gently swirl. Do NOT shake. 
 Vials should be thawed and stored in the original carton until administration in order to protect 

from light. 
 
After thawing 
 
 After thawing, administer Imlygic as soon as practically feasible. 
 Thawed Imlygic is stable when stored at temperatures of 2°C up to 25°C protected from light in 

its original vial, in a syringe, or in the original vial followed by a syringe. Do not exceed the 
storage times specified in table 1 and table 2. 

 If storing thawed Imlygic in the original vial followed by a syringe: 
o the same temperature range should be maintained throughout the duration of storage until 

administration. 
o the storage time in the syringe at ambient temperature up to 25°C cannot exceed 2 hours 

for 106 (1 million) PFU/mL and 4 hours for 108 (100 million) PFU/mL (see table 1). 
o the maximum cumulative storage time (storage time in vial plus storage time in syringe) 

cannot exceed the durations in table 2. 
 Imlygic must not be refrozen once it has thawed. Discard any thawed Imlygic in the vial or 

syringe stored longer than the specified times below. 
 
Table 1. Maximum storage time for thawed Imlygic in syringe 
 

 106 (1 million) PFU/mL 108 (100 million) PFU/mL 
2°C to 8°C 8 hours 8 hours 
up to 25°C 2 hours 4 hours 

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

 106 (1 million) PFU/mL 108 (100 million) PFU/mL 
2°C to 8°C 24 hours 1 week (7 days) 
up to 25°C 12 hours 24 hours 

 
This medicine contains genetically modified organisms. Unused medicine must be disposed of in 
compliance with the institutional guidelines for genetically modified organisms or biohazardous waste, 
as appropriate. 
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE ANDMANUFACTURERS RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETINGAUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE ANDEFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET