Imaavy

HOS-100842 · has-adverse-reaction-information · PDF-Seite 7

Summary of the safety profile The most commonly reported adverse reactions were muscle spasms (12%) and peripheral oedema (12%). Tabulated list of adverse reactions A total of 250 adult gMG patients were treated with nipocalimab in Phase 2 and Phase 3 studies. Of these, 205 patients were treated in the Phase 3 study, including 98 in the double-blind phase. In total, 178 were exposed to the recommended maintenance dose (15 mg/kg every 2 weeks, see section 4.2) for at least 6 months, and 132 were exposed for at least 12 months. Adverse reactions are listed in Table 2 below, classified by MedDRA System Organ Class (SOC). Within each SOC, the adverse reactions are ranked by frequency, with the most frequent reactions first. Frequency categories are defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100) or rare (≥ 1/10 000 to < 1/1 000). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Table 2: Adverse reactions System organ class Adverse reaction Frequency category Infections and infestations Herpes zoster1 Common Urinary tract infection* Common Lower respiratory tract infection*2 Common Metabolism and nutrition Lipids increased*3 Very common disorders Decreased serum albumin* Very common Psychiatric disorders Insomnia Common Nervous system disorders Dizziness Common Gastrointestinal disorders Diarrhoea Common Abdominal pain4 Common Nausea Common Musculoskeletal and Muscle spasms Very Common connective tissue disorders General disorders and Peripheral oedema5 Very Common administration site conditions Pyrexia Common * See paragraph Description of selected adverse reacti

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HOS-100838 · has-contraindication-information · PDF-Seite 3

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

HOS-100837 · has-indication-information · PDF-Seite 2

Imaavy is indicated as an add-on to standard therapy for the treatment of generalised Myasthenia Gravis (gMG) in adult and adolescent patients aged 12 years of age and older who are anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody positive.

HOS-100840 · has-interaction-information · PDF-Seite 5

Effects of nipocalimab on other medicinal products Concomitant use of nipocalimab is likely to reduce systemic exposure of medicinal products that bind to the immunoglobulin G (IgG) binding site of the human neonatal Fc receptor (FcRn) (e.g., IgG products, IgG-based monoclonal antibodies, antibody derivates containing the human Fc domain of the IgG subclass, or Fc fusion proteins). In a dedicated clinical interaction study in healthy participants, nipocalimab (single dose 30 mg/kg intravenously) reduced the systemic Cmax and AUC of fremanezumab (a full IgG-based monoclonal antibody), co-administered on the same day, by 42% and 66%, respectively. When, in this study, the same dose of nipocalimab was administered 14 days after the fremanezumab dose, Cmax of fremanezumab was not altered while its AUC was reduced by 53%. In another dedicated clinical interaction study in healthy participants, concomitant dosing of nipocalimab (15 mg/kg intravenously every 2 weeks) and etanercept, an Fc-fusion protein, reduced etanercept systemic exposure (Cmax by ~9% and AUC by ~28%). If patients on nipocalimab need treatment with medicinal products that bind to the IgG binding site of FcRn, it is recommended these medicinal products are started 2 weeks after the previous dose of nipocalimab. When concomitant long-term use of such medicinal products is essential for patient care, closely monitor for reduced effectiveness of such medicinal products and consider discontinuing nipocalimab or using alternative therapies. Effects of other medicinal products on nipocalimab Plasma exchange, immunoadsorption, and plasmapheresis may reduce circulating levels of nipocalimab. Vaccines The impact of nipocalimab on a T-cell dependent (Tdap) or a T-cell independent (PPSV23) vaccine response was assessed in healthy volunteers (n=16). Participants were able to mount a specific IgG response to these vaccines, but vaccine-specific IgG antibody levels were reduced during nipocalimab treatment with recovery to levels similar to the control group after treatment cessation (see sections 4.4 and 5.1). For patients that are being treated with nipocalimab, vaccination with live or live-attenuated vaccines is not recommended. If vaccination with live or live-attenuated vaccines is required, these vaccines should be administered at least 4 weeks before treatment and at least 2 weeks after the last dose of nipocalimab (see section 4.4).

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HOS-100841 · has-pregnancy-information · PDF-Seite 6

Pregnancy There are limited amount of data from the use of nipocalimab in pregnant women. There is no available data with nipocalimab use in pregnant women with gMG, and limited data from an open-label Phase 2 clinical study in 13 pregnant women at high-risk for Haemolytic Disease of the Foetus and Newborn, in which nipocalimab was studied in the second and third trimesters of pregnancy. In this study, maternal administration of nipocalimab did not result in pharmacologically active concentrations in neonates or infants, due to nipocalimab’s high affinity at neutral (extracellular) pH (see section 5.1). In an animal study where pregnant cynomolgus monkeys were dosed with nipocalimab during the late first, second and third trimesters of pregnancy, large, central placental infarctions and thrombosis of maternal spiral arteries were observed. In some cases, the findings were associated with foetal loss. However, this study does not indicate maternal toxicity or direct or indirect harmful effects on pre- or postnatal development. Reversible nipocalimab-induced reductions in infant monkey IgG levels were demonstrated (see section 5.3). Treatment of pregnant women with Imaavy should only be considered if the clinical benefit outweighs the risks. As nipocalimab is expected to reduce maternal IgG antibody levels, reduction in passive protection to the newborn is anticipated. Risks and benefits should be considered prior to administering live or live-attenuated vaccines to infants exposed to nipocalimab in utero. Breast-feeding There are limited data showing that nipocalimab administered during pregnancy is excreted in colostrum and human milk at low levels for up to 8 days post-partum. Maternal IgG is known to be present in breastmilk during the first days after birth, which decreases to low levels soon thereafter: consequently, a risk to breast-fed infants cannot be excluded during this short period. Afterwards, treatment of breast-feeding women with Imaavy could be considered if the clinical benefit outweighs the risks. Fertility There are no data on the effects of nipocalimab on fertility in humans. Animal studies do not indicate harmful effects with respect to fertility (see section 5.3).

HOS-100839 · has-warning-information · PDF-Seite 3

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. 3 Myasthenia Gravis Foundation of America (MGFA) Class V patients Treatment with nipocalimab in patients with MGFA Class V (i.e., myasthenic crisis), defined as intubation with or without mechanical ventilation except in the setting of routine postoperative care, has not been studied. The sequence of therapy initiation between established therapies for MG crisis and nipocalimab, and their potential interactions, should be considered (see section 4.5). Infusion-related and hypersensitivity reactions Administration of nipocalimab may result in infusion-related and hypersensitivity reactions. The most commonly reported infusion-related reactions were headache, rash, nausea, fatigue, dizziness, chills, and erythema. The most commonly reported hypersensitivity reactions were rash, urticaria and eczema. Most infusion-related and hypersensitivity reactions were non-serious, mild or moderate and did not lead to treatment discontinuation. A case of anaphylaxis has been reported that led to the discontinuation of treatment. The patient should be monitored for 30 minutes after each infusion for clinical signs and symptoms of infusion-related or hypersensitivity reactions. If a serious infusion-related or hypersensitivity reaction occurs during administration, the infusion should be discontinued and appropriate supportive measures should be instituted, if needed. Once resolved, administration may be resumed (see section 4.2). Increased plasma lipid levels Increased plasma lipid levels are very common during treatment with Imaavy, both in adolescent and adult patients of all ages (see section 4.8). Plasma lipid levels should therefore be measured approximately 12 weeks following treatment initiation. In adolescents (12 to <18 years) and in patients with high body weight/BMI (e.g. ≥125 kg or BMI >35 kg/m²), consider closer periodic monitoring thereafter. The evaluation whether to continue treatment with Imaavy should consider the potential negative impact on long-term cardiovascular risk, considering also other risk factors, and weigh this against the expected gMG treatment benefit. Continued monitoring of plasma lipid levels and alternative treatment options should be considered. Infections As nipocalimab causes reduction in IgG levels

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