VYVGART Solution for injection Ref.[116200] 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 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 be administered according to immunisation guidelines.

The safety of immunisation with live or live-attenuated vaccines and the response to immunisation with these vaccines during treatment with efgartigimod alfa are unknown. 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.

Other vaccines may be administered as needed at any time during treatment with efgartigimod alfa.

Immunogenicity

In the active-controlled study ARGX-113-2001, pre-existing antibodies that bind to efgartigimod alfa were detected in 12/110 (11%) patients with gMG. Anti-efgartigimod alfa antibodies were detected in 19/55 (35%) patients treated with efgartigimod alfa subcutaneous compared to 11/55 (20%) patients treated with the intravenous formulation. Neutralising antibodies were detected in 2 (4%) patients treated with efgartigimod alfa subcutaneous and 2 (4%) patients treated with efgartigimod alfa intravenous.

In study ARGX-113-1802, pre-existing antibodies that bind to efgartigimod alfa were detected in 13/317 (4.1%) patients with CIDP. Anti-efgartigimod alfa antibodies were detected in 20/317 (6.3%) of patients treated in the open-label part of the study (Stage A), and in 2/111 (1.8%) of patients treated in the placebo-controlled part (Stage B). Neutralising antibodies were detected in 1 (0.3%) patient in the open-label part of the study only (see section 5.1).

The impact of antibodies to efgartigimod alfa on clinical efficacy or safety, pharmacokinetics and pharmacodynamic cannot be assessed given the low incidence of neutralizing antibodies.

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.

Excipients with known effect

Sodium

This medicinal product contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially 'sodium-free'.

Polysorbates

This medicinal product contains 2.7 mg of polysorbate 20 in each vial which is equivalent to 0.4 mg/mL. Polysorbates may cause allergic reactions.

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).

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 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:

^* See paragraph "Description of selected adverse reactions"
^a From spontaneous post-marketing reporting with intravenous route of administration
^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 studies in gMG with efgartigimod alfa subcutaneous (n=168), all injection site reactions were mild to moderate in severity and did not lead to treatment discontinuation. 44.0% (n=74)) of patients experienced an injection site reaction. Injection site reactions occurred within 24 hours after administration in 78.4% (58/74) of patients and resolved without treatment in 85.1% (63/74) of the patients. The incidence of injection site reactions was the highest in the first treatment cycle, reported in 36.3% (61/168) of patients during the first treatment cycle and decreased to 20.1% (30/149), 15.4% (18/117) and 12.5% (10/80) of patients with the second, third and fourth treatment cycle. In a pooled dataset from 2 clinical studies in patients with CIDP who received continuous administration of efgartigimod alfa subcutaneous the incidence of injection site reactions was 26% (61/235). Analysis by 3-month intervals showed that the percentage of participants with injection-site reactions was highest in the first 3 months of treatment (73 [22.2%] participants) and decreased in subsequent 3-month intervals (range: 0 to 17 [6.8%] participants).

Infections

In the gMG ARGX-113-1704 placebo-controlled study with efgartigimod alfa intravenous, 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 intravenous and 4.8% [n=4] of patients treated with placebo) and urinary tract infections (9.5% [n=8] of patients treated with efgartigimod alfa intravenous and 4.8% [n=4] of patients treated with placebo). These infections were mild to moderate in severity in patients who received efgartigimod alfa intravenous (≤ 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 intravenous 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. In the placebo-controlled part of the ARGX-113-1802 study in patients with CIDP, continuous administration of efgartigimod alfa subcutaneous was not associated with any increase in the incidence of infections (31.5% [35/111] in the efgartigimod alfa subcutaneous group and 33.6% [37/110] in the placebo group) (see section 5.1).

Procedural headache

Procedural headache was reported in 4.8% of the patients treated with efgartigimod alfa intravenous 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.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.