Fremanezumab

There is a limited amount of data from the use of fremanezumab in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. As a precautionary measure, it is preferable to avoid the use of fremanezumab during pregnancy.

It is unknown whether fremanezumab is excreted in human milk. Human 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 fremanezumab could be considered during breast-feeding only if clinically needed.

Fertility

There are no fertility data in humans. Available non-clinical data do not suggest an effect on fertility.

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

Summary of the safety profile

A total of over 2,500 patients (more than 1,900 patient years) have been treated with fremanezumab in registration studies. More than 1,400 patients were treated for at least 12 months.

Commonly reported adverse drug reactions (ADRs) were local reactions at the injection site (pain [24%], induration [17%], erythema [16%] and pruritus [2%]).

List of adverse reactions

ADRs from clinical studies are presented according to MedDRA system organ classification. Within each frequency grouping, ADRs are presented in the order of decreasing seriousness. Frequency categories are based on 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). Within each system organ class, ADRs are ranked by frequency, most frequent reactions first.

The following ADRs have been identified in the fremanezumab clinical development programme.

Adverse reactions in clinical studies:

General disorders and administration site conditions

Very common: Injection site pain, Injection site induration, Injection site erythema

Common: Injection site pruritus

Uncommon: Injection site rash

Description of selected adverse reactions

Injection site reactions

The most frequently observed local reactions at the injection site were pain, induration and erythema. All local injection site reactions were transient and predominantly mild to moderate in severity. Pain, induration and erythema were typically observed immediately after injection while pruritus and rash appeared within a median of 24 and 48 hours, respectively. All injection site reactions resolved, mostly within a few hours or days. Injection site reactions generally did not necessitate discontinuation of the medicinal product.

Immunogenicity

In placebo-controlled studies, 0.4% of patients (6 out of 1,701) treated with fremanezumab developed anti-drug antibodies (ADA). The antibody responses were of low titer. One of these 6 patients developed neutralising antibodies. With 12 months of treatment, ADA were detected in 2.3% of the patients (43 out of 1,888) with 0.95% of the patients developing neutralising antibodies. The safety and efficacy of fremanezumab were not affected by ADA development.