VABYSMO Solution for injection Ref.[50239] Active ingredients: Faricimab

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered medicinal product should be clearly recorded.

Intravitreal injection-related reactions

Intravitreal injections, including those with faricimab, have been associated with endophthalmitis, intraocular inflammation, rhegmatogenous retinal detachment, retinal tear, and iatrogenic traumatic cataract (see section 4.8). Proper aseptic injection techniques must always be used when administering Vabysmo. Patients should be instructed to report any symptoms, such as pain, loss of vision, photophobia, blurred vision, floaters, or redness, suggestive of endophthalmitis or any of the above-mentioned adverse reactions without delay, to permit prompt and appropriate management. Patients with increased frequency of injections may be at increased risk of procedural complications.

Intraocular pressure increases

Transient increases in intraocular pressure (IOP) have been seen within 60 minutes of intravitreal injection, including those with faricimab (see section 4.8). Special precaution is needed in patients with poorly controlled glaucoma (do not inject Vabysmo while the IOP is ≥30 mmHg). In all cases, both the IOP and perfusion of the optic nerve head must be monitored and managed appropriately.

Systemic effects

Systemic adverse events including arterial thromboembolic events have been reported following intravitreal injection of vascular endothelial growth factor (VEGF) inhibitors and there is a theoretical risk that these may be related to VEGF inhibition. A low incidence rate of arterial thromboembolic events was observed in the faricimab clinical trials in patients with nAMD, DME, and RVO. There are limited data on the safety of faricimab treatment in DME patients with high blood pressure (≥140/90 mmHg) and vascular disease, and in nAMD and RVO patients ≥85 years of age.

Immunogenicity

As this is a therapeutic protein, there is a potential for immunogenicity with faricimab (see section 4.8). Patients should be instructed to inform their physician of any signs or symptoms of intraocular inflammation such as vision loss, eye pain, increased sensitivity to light, floaters or worsening eye redness, which might be a clinical sign attributable to hypersensitivity against faricimab (see section 4.8).

Bilateral treatment

The safety and efficacy of faricimab administered in both eyes concurrently have not been studied. Bilateral treatment could cause bilateral ocular adverse reactions and/or potentially lead to an increase in systemic exposure, which could increase the risk of systemic adverse reactions. Until data for bilateral use become available, this is a theoretical risk for faricimab.

Concomitant use of other anti-VEGF

There are no data available on the concomitant use of faricimab with anti-VEGF medicinal products in the same eye. Faricimab should not be administered concurrently with other anti-VEGF medicinal products (systemic or ocular).

Withholding treatment

Treatment should be withheld in patients with:

• Rhegmatogenous retinal detachment, stage 3 or 4 macular holes, retinal break; treatment should not be resumed until an adequate repair has been performed.
• Treatment related decrease in Best Corrected Visual Acuity (BCVA) of ≥30 letters compared with the last assessment of visual acuity; treatment should not be resumed earlier than the next scheduled treatment.
• An intraocular pressure of ≥30 mmHg.
• A subretinal haemorrhage involving the centre of the fovea, or, if the size of the haemorrhage is ≥50%, of the total lesion area.
• Performed or planned intraocular surgery within the previous or next 28 days; treatment should not be resumed earlier than the next scheduled treatment.

Retinal pigment epithelial tear

Retinal pigment epithelial (RPE) tear is a complication of pigment epithelial detachment (PED) in patients with nAMD. Risk factors associated with the development of a retinal pigment epithelial tear after anti-VEGF therapy for nAMD, include a large and/or high pigment epithelial detachment. When initiating faricimab therapy, caution should be used in patients with these risk factors for retinal pigment epithelial tears. RPE tears are common in nAMD patients with PED, treated with intravitreal anti-VEGF agents including faricimab. There was a higher rate of RPE tear in the faricimab group (2.9%) compared to aflibercept group (1.5%). The majority of events occurred during the loading phase, and were mild to moderate, without impact on vision.

Populations with limited data

There is only limited experience in the treatment of nAMD and RVO patients ≥85 years, and DME patients with type I diabetes, patients with HbA1c over 10%, patients with high-risk proliferative diabetic retinopathy (DR), high blood pressure (≥140/90 mmHg) and vascular disease, sustained dosing intervals shorter than every 8 weeks (Q8W), or nAMD, DME, and RVO patients with active systemic infections. There is limited safety information on sustained dosing intervals of 8 weeks or less and these may be associated with a higher risk of ocular and systemic adverse reactions, including serious adverse reactions. There is also no experience of treatment with faricimab in diabetic or RVO patients with uncontrolled hypertension and patients with RVO who have failed previous therapy. This lack of information should be considered by the physician when treating such patients.

Sodium content

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially “sodium-free”.

No interaction studies have been performed. Based on the biotransformation and elimination of faricimab (see section 5.2), no interactions are expected. However, faricimab should not be administered concurrently with other systemic or ocular anti-VEGF medicinal products (see section 4.4).

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.

Pregnancy

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 (see section 5.3).

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

Breast-feeding

It is unknown whether faricimab is excreted in human milk. A risk to the breast-fed newborn/infant cannot be excluded. Vabysmo 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.

Fertility

No effects on reproductive organs or fertility were observed in a 6-month cynomolgus monkey study with faricimab (see section 5.3).

Vabysmo 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%) (see section 4.4).

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 (see section 4.4). 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 (see section 4.4). 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 (see section 4.4). 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.

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.