Zilucoplan

Based on the potential inhibitory effect of zilucoplan on complement-dependent cytotoxicity of rituximab, zilucoplan may reduce the expected pharmacodynamic effects of rituximab.

There are no data from the use of zilucoplan in pregnant women.

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity.

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

It is unknown whether zilucoplan is excreted in human milk or absorbed systemically after oral ingestion by the newborns/infants. A risk to the newborns/infants cannot be excluded.

A decision must be made whether to discontinue breast-feeding or to discontinue zilucoplan therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.

Fertility

The effect of zilucoplan on human fertility has not been evaluated. In some non-human primate fertility and repeat-dose toxicity studies, findings of uncertain clinical relevance were observed in male and female reproductive organs.

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

Summary of the safety profile

The most frequently reported adverse reactions were injection site reactions (injection site bruising (13.9%) and injection site pain (7.0%)) and upper respiratory tract infections (nasopharyngitis (5.2%), upper respiratory tract infection (3.5%) and sinusitis (3.5%)).

Tabulated list of adverse reactions

The table below presents the adverse reactions from the pooled placebo-controlled (n=115) and open-label extension (n=213) studies in gMG together with a classification of the frequency in the zilucoplan treated patients, using the following convention: 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). Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.

Adverse reactions:

^* See paragraph Description of selected adverse reactions.
^a Morphoea was reported only in long-term open-label clinical studies. The maximum duration of exposure to ZLP during the long-term clinical studies was more than 4 years.

Description of selected adverse reactions

Injection site reactions

The most common reactions were injection site bruising, pain, nodule, pruritus and haematoma. All cases were mild or moderate in severity, and less than 3% of reactions led to treatment discontinuation.

Upper respiratory tract infections

The most common infections were nasopharyngitis, upper respiratory tract infection and sinusitis. More than 95% of the cases were mild or moderate in severity and did not lead to treatment discontinuation. In pooled placebo-controlled studies, upper respiratory tract infections were reported in 13.0% of patients treated with zilucoplan and in 7.8% of patients treated with placebo.

Pancreatic enzymes increased

Cases of lipase increase (5.2%) and/or amylase increase (6.1%) were observed. These elevations were transient and rarely led to treatment discontinuation. The majority occurred within 2 months of starting zilucoplan and normalized within 2 months.

Blood eosinophils increased

Elevations of blood eosinophils were observed. These were transient and not leading to treatment discontinuation. The majority occurred within 2 months of starting zilucoplan and normalized within 1 month.

Morphoea

Cases of morphoea were observed after long-term treatment during the open-label extension study. The majority of the cases had a time to onset longer than one year after start of treatment, were mild or moderate in severity and did not lead to treatment discontinuation.