Faricimab

There are no or limited amount of data from the use of faricimab in pregnant women. The systemic exposure to faricimab is low after ocular administration, but due to its mechanism of action (i.e. VEGF inhibition), faricimab must be regarded as potentially teratogenic and embryo-/foetotoxic.

Faricimab should not be used during pregnancy unless the potential benefit outweighs the potential risk to the foetus.

It is unknown whether faricimab is excreted in human milk. A risk to the breast-fed newborn/infant cannot be excluded. Faricimab should not be used during breast-feeding. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from faricimab therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Women of childbearing potential

Women of childbearing potential should use effective contraception during treatment and for at least 3 months following the last intravitreal injection of faricimab.

Fertility

No effects on reproductive organs or fertility were observed in a 6-month cynomolgus monkey study with faricimab.

Faricimab has a minor influence on the ability to drive and use machines. Temporary visual disturbances may occur following the intravitreal injection and the associated eye examination. Patients should not drive or use machines until visual function has recovered sufficiently.

Summary of the safety profile

The most frequently reported adverse reactions were cataract (10%), conjunctival haemorrhage (7%), vitreous detachment (4%), IOP increased (4%), vitreous floaters (4%), eye pain (3%), and retinal pigment epithelial tear (nAMD only) (3%).

The most serious adverse reactions were uveitis (0.5%), endophthalmitis (0.4%), vitritis (0.4%), retinal tear (0.2%), rhegmatogenous retinal detachment (0.1%), and traumatic cataract (<0.1%).

Tabulated list of adverse reactions

The adverse reactions reported in clinical studies or during post-marketing surveillance are listed according to the MedDRA system organ class and ranked by frequency 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) or not known (frequency cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Table 1. Frequencies of adverse reactions:

Terms marked with asterisk (*) are adverse reactions which have been identified based on post-marketing spontaneous reports. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency.

Description of selected adverse reactions

Retinal Vasculitis and Retinal Occlusive Vasculitis

Rare cases of retinal vasculitis and/or retinal occlusive vasculitis have been spontaneously reported in the post-marketing setting. Retinal vasculitis and retinal occlusive vasculitis have also been reported in patients treated with IVT therapies.

Product-class-related adverse reactions

There is a theoretical risk of arterial thromboembolic events, including stroke and myocardial infarction, following intravitreal use of VEGF inhibitors. A low incidence rate of arterial thromboembolic events was observed in the faricimab clinical trials in patients with nAMD, DME, and RVO. Across indications, no notable difference between the groups treated with faricimab and the comparator were observed.

Immunogenicity

There is a potential for an immune response in patients treated with faricimab. After dosing with faricimab for up to 112 (nAMD), 100 (DME), and 72 (RVO) weeks, treatment-emergent anti-faricimab antibodies were detected in approximately 13.8%, 9.6%, and 14.4% of patients with nAMD, DME, and RVO randomised to faricimab, respectively. The clinical significance of anti- faricimab antibodies on safety is unclear at this time. The incidence of intraocular inflammation in anti-faricimab antibody positive patients was 12/98 (12.2%; nAMD), 15/128 (11.7%; DME), and 9/95 (9.5%; RVO), and in anti-faricimab antibody negative patients was 8/562 (1.4%; nAMD), 5/1124 (0.4%; DME), and 10/543 (1.8%; RVO). The incidence of serious ocular adverse reactions in anti-faricimab antibody positive patients was 6/98 (6.1%; nAMD), 14/128 (10.9%; DME), and 7/95 (7.4%; RVO), and in anti-faricimab antibody negative patients was 23/562 (4.1%; nAMD), 45/1124 (4.0%; DME), and 34/543 (6.3%; RVO). Anti-faricimab antibodies were not associated with an impact on clinical efficacy or systemic pharmacokinetics.