Imlygic · 4.6 Fertility, pregnancy and lactation · 1

HOS-216546 · has-adverse-reaction-information · PDF-Seite 9

Summary of the 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, 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). 9 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. Table 3. Adverse reactions from clinical trials in patients with melanoma and post-marketing experience Infections and infestations Common Cellulitis*, Herpes infections** 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

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HOS-216542 · has-contraindication-information · PDF-Seite 6

• 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).

HOS-216541 · has-indication-information · PDF-Seite 3

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).

HOS-216544 · has-interaction-information · PDF-Seite 8

No interaction studies have been conducted with Imlygic. Acyclovir and other anti-viral agents may interfere with the effectiveness of the treatment 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.

HOS-216545 · has-pregnancy-information · PDF-Seite 8

Women of childbearing potential/contraception Women of childbearing potential should be advised to use an effective method of contraception to prevent pregnancy during treatment. All patients should be advised to use a latex condom during sexual contact to prevent possible transmission of Imlygic (see section 4.4). 8 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. 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 the medicinal product, 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).

HOS-216543 · has-warning-information · PDF-Seite 6

Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Previously treated patients Efficacy data for Imlygic in the current second or later line treatment settings are limited. Disseminated herpetic infection Disseminated herpetic infection, including serious cases of disseminated herpetic infection, have been reported in patients treated with Imlygic (see section 4.8). Imlygic has not been studied in immunocompromised patients. Based on epidemiological data, immunocompromised patients (such as those with HIV/AIDS, leukaemia, lymphoma, common variable immunodeficiency, or who require chronic high-dose steroids or other immunosuppressive agents) may be at increased risk of disseminated herpetic infection. Consider the risks and benefits of treatment before administering Imlygic to 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). 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. 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 6 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

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