Vyvgart · 4.3 Contraindications · 2

HOS-100164 · has-adverse-reaction-information · PDF-Seite 19

Summary of the safety profile The most frequently observed adverse reactions were injection site reactions (33%), upper respiratory tract infections (10.7%) and urinary tract infections (9.5%). The overall safety profile of Vyvgart subcutaneous for both cyclic and continuous dose regimens was consistent with the known safety profile of the intravenous formulation. Tabulated list of adverse reactions Adverse reactions described in this section were identified in clinical trials and from post-marketing reports. These reactions are presented by system organ class and preferred term. Frequency categories are defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100), rare (≥ 1/10 000 to < 1/1 000) or not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Table 1. Adverse reactions System organ class Adverse reaction Frequency category Infections and infestations* Upper respiratory tract infections Very common Urinary tract infections Common Bronchitis Common Immune system disorders Anaphylactic reaction a Not known Gastrointestinal disorders Nausea b Common Musculoskeletal and connective Myalgia Common tissue disorders General disorders and Injection site reactions c, d Very common administration site conditions* Injury, poisoning and Procedural headache e Common procedural complications* * See paragraph “Description of selected adverse reactions” a From spontaneous post-marketing reporting with intravenous route of administration 19 b From spontaneous post-marketing reporting. c Subcutaneous administration only. d (e.g. injection site rash, injection site erythema, injection site pruritus, injection site pain) e Intravenous administration only. Description of selected adverse reactions Injection site reactions In the pooled dataset from two clinical stud

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HOS-100158 · has-adverse-reaction-information · PDF-Seite 6

Summary of the safety profile The most frequently observed adverse reactions were upper respiratory tract infections and urinary tract infections (10.7% and 9.5%, respectively). Tabulated list of adverse reactions The safety of Vyvgart was evaluated in 167 patients with gMG in the Phase 3 double-blind placebo-controlled clinical study. Adverse reactions are listed in Table 1 by system organ class and preferred term. Frequency categories are defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100). rare (≥ 1/10 000 to < 1/1 000) or not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Table 1. Adverse reactions System organ class Adverse reaction Frequency category Infections and infestations* Upper respiratory tract infections Very common Urinary tract infections Common Bronchitis Common Immune system disorders Anaphylactic reaction a Not known 6  System organ class Adverse reaction Frequency category Gastrointestinal disorders Nausea a Common Musculoskeletal and Myalgia Common connective tissue disorders Injury, poisoning and Procedural headache Common procedural complications* * See paragraph “Description of selected adverse reactions” a From spontaneous post-marketing reporting Description of selected adverse reactions Infections The most frequently reported adverse reactions were infections, and the most reported infections were upper respiratory tract infections (10.7% [n = 9] of patients treated with efgartigimod alfa and 4.8% [n = 4] of patients treated with placebo) and urinary tract infections (9.5% [n = 8] of patients treated with efgartigimod alfa and 4.8% [n = 4] of patients treated with placebo). These infections were mild to moderate in severity in patients who received efgartigimod alfa (≤ Grade 2 according to the Common Terminology Criteria for Adverse Events). Overall, treatment emergent infections were

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HOS-100154 · has-contraindication-information · PDF-Seite 4

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

HOS-100160 · has-contraindication-information · PDF-Seite 16

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

HOS-100159 · has-indication-information · PDF-Seite 14

Vyvgart is indicated as - an add-on to standard therapy for the treatment of adult patients with generalised Myasthenia Gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody positive. - monotherapy for the treatment of adult patients with progressive or relapsing active chronic inflammatory demyelinating polyneuropathy (CIDP) after prior treatment with corticosteroids or immunoglobulins.

HOS-100153 · has-indication-information · PDF-Seite 2

Vyvgart is indicated as an add-on to standard therapy for the treatment of adult patients with generalised Myasthenia Gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody positive.

HOS-100156 · has-interaction-information · PDF-Seite 5

No interaction studies have been performed. Efgartigimod alfa may decrease concentrations of compounds that bind to the human neonatal Fc Receptor (FcRn), i.e., immunoglobulin products, monoclonal antibodies, or antibody derivatives containing the human Fc domain of the IgG subclass. If possible, it is recommended to postpone initiation of treatment with these products to 2 weeks after the last dose of any given treatment cycle of Vyvgart. As a precaution, patients receiving Vyvgart while on treatment with these products should be closely monitored for the intended efficacy response of those products. Plasma exchange, immunoadsorption, and plasmapheresis may reduce circulating levels of efgartigimod alfa. All vaccines should be administered according to immunisation guidelines. The potential interaction with vaccines was studied in a nonclinical model using Keyhole limpet hemocyanin (KLH) as the antigen. The weekly administration of 100 mg/kg to monkeys did not impact the immune response to KLH immunisation. For patients that are being treated with efgartigimod alfa, vaccination with live or live-attenuated vaccines is generally 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 a treatment cycle efgartigimod alfa (see section 4.4). 5

HOS-100162 · has-interaction-information · PDF-Seite 18

No interaction studies have been performed. Efgartigimod alfa may decrease concentrations of compounds that bind to the human neonatal Fc Receptor (FcRn), i.e., immunoglobulin products, monoclonal antibodies, or antibody derivatives containing the human Fc domain of the IgG subclass. If possible, it is recommended to postpone the initiation of treatment with these products to 2 weeks after the last dose of Vyvgart. As a precaution, patients receiving Vyvgart while on treatment with these products should be closely monitored for the intended efficacy response of those products. Plasma exchange, immunoadsorption, and plasmapheresis may reduce circulating levels of efgartigimod alfa. All vaccines should be administered according to immunisation guidelines. The potential interaction with vaccines was studied in a nonclinical model using Keyhole limpet hemocyanin (KLH) as the antigen. The weekly administration of 100 mg/kg to monkeys did not impact the immune response to KLH immunisation. For patients that are being treated with efgartigimod alfa, vaccination with live or live-attenuated vaccines is generally 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 efgartigimod alfa (see section 4.4).

HOS-100157 · has-pregnancy-information · PDF-Seite 6

Pregnancy There is no available data on the use of efgartigimod alfa during pregnancy. Antibodies including therapeutic monoclonal antibodies are known to be actively transported across the placenta (after 30 weeks of gestation) by binding to the FcRn. Efgartigimod alfa may be transmitted from the mother to the developing foetus. As efgartigimod alfa is expected to reduce maternal antibody levels, and is also expected to inhibit the transfer of maternal antibodies to the foetus, reduction in passive protection to the newborn is anticipated. Therefore, risks and benefits of administering live/live-attenuated vaccines to infants exposed to efgartigimod alfa in utero should be considered (see section 4.4). Treatment of pregnant women with Vyvgart should only be considered if the clinical benefit outweighs the risks. Breast-feeding There is no information regarding the presence of efgartigimod alfa in human milk, the effects on the breastfed child or the effects on milk production. Animal studies on the transfer of efgartigimod alfa into milk have not been conducted, and therefore, excretion into maternal milk cannot be excluded. Maternal IgG is known to be present in human milk. Treatment of lactating women with efgartigimod alfa should only be considered if the clinical benefit outweighs the risks. Fertility There is no available data on the effect of efgartigimod alfa on fertility in humans. Animal studies showed no impact of efgartigimod alfa on male and female fertility parameters (see section 5.3).

HOS-100163 · has-pregnancy-information · PDF-Seite 18

Pregnancy There is no available data on the use of efgartigimod alfa during pregnancy. Antibodies including therapeutic monoclonal antibodies are known to be actively transported across the placenta (after 30 weeks of gestation) by binding to FcRn. Efgartigimod alfa may be transmitted from the mother to the developing foetus. As efgartigimod alfa is expected to reduce maternal antibody levels, and is also expected to inhibit the transfer of maternal 18 antibodies to the foetus, reduction in passive protection to the newborn is anticipated. Therefore, risks and benefits of administering live/live-attenuated vaccines to infants exposed to efgartigimod alfa in utero should be considered (see section 4.4). Treatment of pregnant women with Vyvgart should only be considered if the clinical benefit outweighs the risks. Breast-feeding There is no information regarding the presence of efgartigimod alfa in human milk, the effects on the breastfed child or the effects on milk production. Animal studies on the transfer of efgartigimod alfa into milk have not been conducted, and therefore, excretion into maternal milk cannot be excluded. Maternal IgG is known to be present in human milk. Treatment of lactating women with efgartigimod alfa should only be considered if the clinical benefit outweighs the risks. Fertility There is no available data on the effect of efgartigimod alfa on fertility in humans. Animal studies showed no impact of efgartigimod alfa on male and female fertility parameters (see section 5.3).

HOS-100155 · has-warning-information · PDF-Seite 4

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. Myasthenia Gravis Foundation of America (MGFA) Class V patients Treatment with efgartigimod alfa 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 efgartigimod alfa, and their potential interactions, should be considered (see section 4.5). Infections As efgartigimod alfa causes transient reduction in IgG levels the risk of infections may increase (see sections 4.8 and 5.1). The most common infections observed in clinical trials were upper respiratory tract infections and urinary tract infections (see section 4.8). Patients should be monitored for clinical signs and symptoms of infections during treatment with Vyvgart. In patients with an active infection, the benefit-risk of maintaining or withholding treatment with efgartigimod alfa should be considered until the infection has resolved. If serious infections occur, delaying treatment with efgartigimod alfa should be considered until the infection has resolved. Infusion reactions and hypersensitivity reactions Infusion reactions such as rash or pruritus may occur. In the clinical trial, infusion reactions were mild to moderate and did not lead to treatment discontinuation. Patients should be monitored during administration and for 1 hour thereafter for clinical signs and symptoms of infusion reactions. Should a reaction occur and based on the severity of the reaction the infusion should be administered at a slower rate, interrupted or discontinued and appropriate supportive measures should be instituted. Once resolved, administration may be cautiously resumed, based on clinical evaluation. Cases of anaphylactic reaction have been reported in the post-marketing setting. If an anaphylactic reaction is suspected, administration of Vyvgart should be immediately discontinued and appropriate medical treatment initiated. Patients should be informed of the signs and symptoms of hypersensitivity and anaphylactic reactions and advised to contact their healthcare provider immediately should they occur. Immunisations All vaccines should be administered according to immunisation guidelines. The safety of immunisation with

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HOS-100161 · has-warning-information · PDF-Seite 16

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. 16 Myasthenia Gravis Foundation of America (MGFA) Class V patients Treatment with efgartigimod alfa 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 efgartigimod alfa, and their potential interactions, should be considered (see section 4.5). Infections As efgartigimod alfa causes transient reduction in IgG levels the risk of infections may increase (see sections 4.8 and 5.1). The most common infections observed in clinical trials were upper respiratory tract infections and urinary tract infections (see section 4.8). Patients should be monitored for clinical signs and symptoms of infections during treatment with Vyvgart. In patients with an active infection, the benefit-risk of maintaining or withholding treatment with efgartigimod alfa should be considered until the infection has resolved. If serious infections occur, delaying treatment with efgartigimod alfa should be considered until the infection has resolved. Injection reactions and hypersensitivity reactions Injection reactions such as rash or pruritus were reported in the clinical trials (see section 4.8). These were mild to moderate. Cases of anaphylactic reaction have been reported with efgartigimod alfa intravenous in the post-marketing setting. The first administrations of Vyvgart must be performed under the supervision of a healthcare professional (see section 4.2). Patients should be monitored for 30 minutes after administration for clinical signs and symptoms of injection reactions. Should a reaction occur and based on the severity of the reaction, appropriate supportive measures should be initiated. Subsequent injections may be cautiously administered, based on clinical evaluation. If an anaphylactic reaction is suspected, administration of Vyvgart should be immediately discontinued and appropriate medical treatment initiated. Patients should be informed of the signs and symptoms of hypersensitivity and anaphylactic reactions and advised to contact their healthcare professional immediately should they occur. Immunisations All vaccines should

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