Efgartigimod alfa

Limited safety and efficacy data in patients with mild renal impairment is available, no doseadjustment is required for patients with mild renal impairment. There is very limited safety and efficacy data in patients with moderate or severe renal impairment.

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 efgartigimod alfa. As a precaution, patients receiving efgartigimod alfa 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.

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.

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.

Treatment of pregnant women with efgartigimod alfa should only be considered if the clinical benefit outweighs the risks.

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.

Efgartigimod alfa 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 efgartigimod alfa 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.

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).

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).