VYVGART Concentrate for solution for infusion Ref.[50188] Active ingredients: Efgartigimod alfa

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 section 4.8 and section 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

Infusion reactions such as rash or pruritus may occur. In the clinical trial, these were mild to moderate and did not lead to treatment interruption or discontinuation. Patients should be monitored during administration and for 1 hour thereafter for clinical signs and symptoms of infusion reactions. Should a reaction occur the infusion should be interrupted and appropriate supportive measures should be instituted. Once resolved, administration may be resumed, if needed at a slower rate (see section 4.2).

Immunisations

Immunisation with vaccines during efgartigimod alfa therapy has not been studied. The safety of immunisation with live or live-attenuated vaccines and the response to immunisation with vaccines are unknown. All vaccines should be administered according to immunisation guidelines and at least 4 weeks before initiation of treatment. For patients that are on treatment, vaccination with live or live-attenuated vaccines is not recommended. For all other vaccines, they should take place at least 2 weeks after the last infusion of a treatment cycle and 4 weeks before initiating the next cycle.

Immunogenicity

In the double-blind placebo-controlled study, pre-existing antibodies that bind to efgartigimod alfa were detected in 25/165 (15%) patients with gMG. Treatment-induced antibodies to efgartigimod alfa were detected in 17/83 (21%) patients. In 3 of these 17 patients, treatment-induced anti-drug antibodies (ADAs) persisted until the end of the study. Neutralising antibodies were detected in 6/83 (7%) of patients treated with Vyvgart, including the 3 patients with persisting treatment-induced ADAs. Retreatment did not cause an increase in incidence or titres of efgartigimod alfa antibodies.

There was no apparent impact of antibodies to efgartigimod alfa on clinical efficacy or safety, nor on pharmacokinetics and pharmacodynamic parameters.

Immunosuppressant and anticholinesterase therapies

When non-steroidal immunosuppressants, corticosteroids and anticholinesterase therapies are decreased or discontinued, patients should be monitored closely for signs of disease exacerbation.

Sodium content

This medicinal product contains 67.2 mg sodium per vial, equivalent to 3.4% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

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.

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. Nevertheless, all vaccines should be administered according to immunisation guidelines and at least 4 weeks before initiation of a treatment cycle and not until 2 weeks after the last infusion of a treatment cycle. For patients that are on treatment, vaccination with live or live-attenuated vaccines is not recommended (see section 4.4).

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).

Vyvgart has no or negligible influence on the ability to drive and use machines.

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) or rare (≥1/10 000 to <1/1 000). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Table 1. Adverse reactions:

^* See paragraph "Description of selected adverse reactions"

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 reported in 46.4% (n=39) of patients treated with efgartigimod alfa and 37.3% (n=31) of patients treated with placebo. The median time from treatment initiation to emergence of infections was 6 weeks. Incidence of infections did not increase with subsequent treatment cycles. Treatment discontinuation or temporary interruption of treatment due to an infection occurred in less than 2% of patients.

Procedural headache

Procedural headache was reported in 4.8% of the patients treated with efgartigimod alfa and 1.2% of patients treated with placebo. Procedural headache was reported when a headache was judged to be temporally related to the intravenous infusion of efgartigimod alfa. All were mild or moderate except one event which was reported as severe (Grade 3).

All other adverse reactions were mild or moderate with the exception of one case of myalgia (Grade 3).

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.

This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.