RYSTIGGO Solution for injection Ref.[108735] Active ingredients: Rozanolixizumab

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.

Myasthenic crisis

Treatment with rozanolixizumab in patients with impending or manifest myasthenic crisis has not been studied. The sequence of therapy initiation between established therapies for MG crisis and rozanolixizumab, and their potential interactions, should be considered (see section 4.5).

Aseptic meningitis

Aseptic meningitis (drug induced aseptic meningitis) has been reported following rozanolixizumab treatment at a higher dose with subsequent recovery without sequelae after discontinuation. If symptoms consistent with aseptic meningitis (headache, pyrexia, neck stiffness, nausea, vomiting) occur, diagnostic workup and treatment should be initiated as per standard of care.

Infections

As rozanolixizumab causes transient reduction in IgG levels the risk of infections may increase (see section 5.1). Upper respiratory tract infections and herpes simplex infections have been observed with a higher dose of rozanolixizumab. Overall, in phase 3 studies in gMG, infections were reported in 45.2% of all rozanolixizumab treated patients. No increase in the incidence of infections was observed from cycle to cycle. Serious infections were reported in 4.3% of patients. Treatment with rozanolixizumab should not be initiated in patients with a clinically important active infection until the infection resolves or is adequately treated. During treatment with rozanolixizumab, clinical signs and symptoms of infections should be monitored. If a clinically important active infection occurs, withholding rozanolixizumab until the infection has resolved should be considered.

Hypersensitivity

Infusion reactions such as rash or angioedema may occur (see section 4.8). In the clinical trial, these were mild to moderate. Patients should be monitored during treatment with rozanolixizumab and for 15 minutes after the administration is complete for clinical signs and symptoms of hypersensitivity reactions. If a hypersensitivity reaction occurs during administration (see section 4.8), rozanolixizumab infusion should be discontinued and appropriate measures should be initiated if needed. Once resolved, administration may be resumed.

Vaccination

Immunisation with vaccines during rozanolixizumab 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 pooled cyclic treatment data from the phase 3 program, after 1 treatment cycle of 6 rozanolixizumab weekly doses, 27.1% (42/155) of patients developed antidrug antibodies and 10.3% (16/155) had antibodies that were classified as neutralising. Upon reinitiating therapy, the proportion of patients who developed antidrug antibodies and neutralising antibodies increased to 65% (13/20) and 50% (10/20) respectively, after 5 treatment cycles. Development of neutralising antibodies was associated with a 24% decrease in overall plasma exposure of rozanolixizumab. There was no apparent impact of immunogenicity on efficacy and safety (see sections 5.1 and 5.2).

Excipients

This medicinal product contains 29 mg of proline in each ml.

The use in patients suffering from hyperprolinaemia should be restricted where no alternative treatment is available.

No interaction studies have been performed.

As rozanolixizumab interferes with the FcRn recycling mechanism of immunoglobulin G (IgG), the serum concentrations of IgG-based medicinal products (e.g. monoclonal antibodies and intravenous immunoglobulin [IVIg]) and Fc–peptide fusion proteins are expected to be decreased if administered concomitantly or within 2 weeks after administration of rozanolixizumab. It is recommended to initiate these treatments 2 weeks after administration of rozanolixizumab and to monitor for attenuated efficacy of these medicinal products when administered concomitantly.

Treatment with IV or SC immunoglobulins, PLEX/plasmapheresis and immunoadsorption may reduce circulating levels of rozanolixizumab.

Vaccination during treatment with rozanolixizumab has not been studied and the response to any vaccine is unknown. Because rozanolixizumab causes a reduction in IgG levels, vaccination with live-attenuated or live vaccines is not recommended during treatment with rozanolixizumab (see sections 4.4 and 5.3).

Pregnancy

There are limited amount of data from the use of rozanolixizumab in pregnant women. In animal studies, offspring from treated dams had very low levels of IgG at birth, as expected by the pharmacological mode of action of rozanolixizumab (see section 5.3). However, animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonic/foetal development, parturition or postnatal development. Treatment of pregnant women with rozanolixizumab should only be considered if the clinical benefit outweighs the risks.

As rozanolixizumab 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 rozanolixizumab in utero should be considered (see section 4.4, subsection “Vaccination”).

Breast-feeding

It is unknown whether rozanolixizumab is excreted in human milk. Maternal IgG is known to be excreted in breast milk during the first days after birth, which is decreasing to low concentrations soon afterwards; consequently, a risk to breast-fed infants cannot be excluded during this short period. Afterwards, use of rozanolixizumab could be considered during breast-feeding only if the clinical benefit outweighs the risks.

Fertility

The effect of rozanolixizumab on human fertility is not known. Animal studies do not indicate harmful effects with respect to fertility (see section 5.3).

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

Summary of the safety profile

The most commonly reported adverse reactions were headache (48.4%), diarrhoea (25.0%) and pyrexia (12.5%).

Tabulated list of adverse reactions

Adverse reactions from clinical studies in gMG are listed in Table 1 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 follows: 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); Very rare (<1/10 000), not known (cannot be estimated from the available data).

Table 1. List of adverse reactions:

¹ Includes headache and migraine.
² Includes rash, rash papular and rash erythematous 3 Includes swollen tongue 4 Includes injection site rash, reaction, erythema, inflammation, discomfort, and infusion site erythema, pain.

Description of selected adverse reactions

Headache

In MG0003, headache was the most common reaction reported in 31 (48.4%) and 13 (19.4%) of the patients treated with rozanolixizumab and placebo, respectively. Headache occurred most frequently after the first infusion of rozanolixizumab and within 1 to 4 days after infusion. Except for 1 (1.6%) severe headache, all headaches were either mild (28.1% [n=18]) or moderate (18.8% [n=12]) and there was no increase in incidences of headache with repeated cyclic treatment.

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 for infusion.