Faricimab

Registered South African indications:

• Neovascular (wet) age-related macular degeneration (nAMD)
• Diabetic macular oedema (DME)
• Macular oedema secondary to retinal vein occlusion (RVO)

Registered South African contraindications

• Hypersensitivity to the active ingredient or any of its excipients
  - May present as rash, pruritus, urticaria, erythema, or severe intraocular inflammation
• Ocular or periocular infections
• Active intraocular inflammation

Caution in the following patient groups

• Pregnancy
• Breastfeeding
• Women of childbearing age

General

• To ensure the traceability of biological medicinal products, the name and batch number of the administered product must be clearly recorded

Sucrose content

• Faricimab contains D sucrose. Patients with the rare hereditary conditions of galactose intolerance lactase deficiency, glucose-galactose malabsorption intolerance should not take faricimab
• Faricimab contains D sucrose which may have an effect on the glycaemic control of patients with diabetes mellitus

Intravitreal injection-related reactions

• Special precautions are necessary for patients receiving intravitreal injections, as there is a risk of adverse events including endophthalmitis, intraocular inflammation, retinal detachment/tear, and iatrogenic traumatic cataract. Aseptic injection techniques must be used, and the patient should be instructed to immediately report symptoms like pain, loss of vision, or redness
• There is a transient increase in intraocular pressure (IOP) within 60 minutes of injection; therefore, this medicine should not be injected if the patient has an IOP ≥30mmHg or poorly controlled glaucoma, requiring monitoring of IOP and optic nerve head perfusion

Systemic effects

• Intravitreal injection of vascular endothelial growth factor (VEGF) inhibitors is associated with a theoretical risk of systemic adverse events, including arterial thromboembolic events, potentially related to VEGF inhibition, although a low incidence rate was observed in clinical trials

Immunogenicity

• As this is a therapeutic protein, there is a potential for immunogenicity (the development of an immune response) with faricimab; patients should report any signs or symptoms of intraocular inflammation (e.g., vision loss, eye pain, or worsening eye redness), which may be indicative of a hypersensitivity reaction

Bilateral treatment

• The safety and efficacy of faricimab administered concurrently in both eyes have not been established

Concomitant use of other anti-VEGF

• There is no available data regarding the concomitant use of faricimab with other anti-VEGF medicinal products in the same eye

Withholding treatment

• Treatment with faricimab must be withheld in patients with a rhegmatogenous retinal detachment, stage 3 or 4 macular holes, or a retinal break, and it should not resume until an adequate repair is performed. Treatment must also be withheld if there is a treatment-related decrease in Best Corrected Visual Acuity (BCVA) of ≥30 letters compared with the last assessment, or if the patient had performed or planned intraocular surgery within the previous or next 28 days; in these cases, treatment should not be resumed earlier than the next scheduled treatment

Retinal pigment epithelial tear

• Caution is necessary when initiating anti-VEGF therapy with faricimab in patients with risk factors for a retinal pigment epithelial tear specifically, those with a large and/or high pigment epithelial detachment, as these pre-existing conditions increase the risk of this adverse event

Populations with limited data

• Physicians should consider the limited clinical experience when treating patients who have diabetic macular edema (DME) with HbA1c over 10%, high-risk proliferative diabetic retinopathy (DR), or patients with neovascular age-related macular degeneration (nAMD), DME, or retinal vein occlusion (RVO) who have active systemic infections. Additionally, there is no experience treating diabetic or RVO patients with uncontrolled hypertension

Drug abuse and dependence

• There is no evidence that faricimab has the potential for drug abuse and dependence

Effects on ability to drive and use machines

• Faricimab may have a minor influence on the ability to drive and use machines due to possible temporary visual disturbances following the intravitreal injection and the associated eye examination
• Patients should not drive or use machines until visual function has recovered sufficiently

Forms avail. in SA and covered in this monograph: inj

South African registered indications and dosages

For intravitreal injection only. Faricimab must be administered by a qualified physician experienced in intravitreal injections. Each vial should only be used for the treatment of a single eye

Neovascular (wet) age-related macular degeneration (nAMD)

• Intravitreal (inj): First 4 doses: 6mg, every 4 weeks (monthly); Thereafter: Assess anatomic or visual outcomes at 20 and/or 24 weeks after initiation to guide individualised treatment; In patients without disease activity: Admin. every 16 weeks (4 months) should be considered; In patients with disease activity: Treatment every 8 weeks (2 months) or 12 weeks (3 months) should be considered;  Adjust interval as outcomes change; shorten if deterioration occurs

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There is limited safety data on treatment intervals of 8 weeks or less between injections

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Diabetic macular oedema (DME)

• Intravitreal (inj): First 4 doses: 6mg, every 4 weeks (monthly); Thereafter: Individualise using a treat-and-extend approach; Dosing interval may be extended up to every 16 weeks (4 months) based on patient’s anatomic and/or visual outcomes, in increments of up to 4 weeks; Adjust interval as outcomes change; shorten if deterioration occurs

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Treatment intervals shorter than 4 weeks between injections have not been studied

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Macular oedema secondary to retinal vein occlusion (RVO)

• Intravitreal (inj): 6mg, every 4 weeks (monthly); 3 or more consecutive, monthly injections may be needed; Followed by: 6mg, at intervals of up to every 16 weeks (4 months)

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Applicable to all indications
Monitoring between the dosing visits should be scheduled based on the patient's status and at the physician's discretion, but there is no requirement for monthly monitoring between injections

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Duration of treatment: Faricimab is intended for long-term treatment

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Method of administration
Faricimab should be inspected visually for particulate matter and discolouration prior to administration. Immediately following the intravitreal injection, patients should be monitored for elevation in intraocular pressure. Appropriate monitoring may consist of a check for perfusion of the optic nerve head or tonometry. If required, sterile equipment for paracentesis should be available. Following intravitreal injection patients should be instructed to report any symptoms suggestive of endophthalmitis (e.g. vision loss, eye pain, redness of the eye, photophobia, blurring of vision) without delay. For comprehensive instructions for the administration of faricimab, refer to the product's professional information usually included in its packaging

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Delayed or missed dose
If a dose is delayed or missed, the patient should return to be assessed by physician at the next available visit and continue dosing depending on physician’s discretion. If visual and/or anatomic outcomes indicate that the patient is not benefitting from continued treatment, faricimab should be discontinued

Not established for use in children and adolescents

Pregnancy

South African recommendations

• Caution; not recommended
• There are no data from the use of faricimab in pregnant women
• No adverse effects were observed in a study in pregnant cynomologus monkeys given faricimab intravenously throughout the period of organogenesis at doses achieving more than 500 times the predicted systemic human exposure of faricimab after treatment of a single eye
• It is not known whether faricimab can cross the placenta or cause harm to the foetus when administered to pregnant women. Based on the mechanism of action of VEGF and Ang-2 inhibitors, there is a potential risk to female reproductive capacity, and to embryo-foetal development
• Although the systemic exposure after ocular administration is very low, faricimab should not be used during pregnancy unless the potential benefit to the patient outweighs the potential risk to the foetus

Labor and delivery

• The safe use of faricimab during labor and delivery has not been established

Women of childbearing potential

• Women of childbearing potential should use contraception during treatment with faricimab and for at least 3 months following the last dose of faricimab

Breastfeeding

South African recommendations

• Caution
• It is not known whether faricimab is excreted in human breast milk
• No studies have been conducted to assess the impact of faricimab on milk production or its presence in breast milk because many drugs are excreted in human milk with the potential for absorption and harm to infant growth and development exists, caution should be exercised when faricimab is administered to a nursing woman
• The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for faricimab and any potential adverse effects on the breastfed child from faricimab

Fertility

South African recommendations

• No reproductive or fertility studies have been conducted. No effects on reproductive organs or fertility were observed in a 6-month cynomolgus monkey study with faricimab
• VEGF inhibition has been shown to affect follicular development, corpus luteum function and fertility
• Based on the mechanism of action of VEGF and Ang-2 inhibitors, there is a potential risk to female reproductive capacity, and to embryo-foetal development, however the risk is considered low due to the low systemic exposure after ocular administration

South African recommendations

• No dose adjustment recommended

South African recommendations

• No dose adjustment recommended

South African recommendations

• No dose adjustment recommended

Eye disorders

Common

• Cataract
• Conjunctival haemorrhage
• Vitreous detachment
• Intraocular pressure increased
• Vitreous floaters
• Retinal pigment epithelial tear (nAMD only)
• Eye pain

Uncommon

• Corneal abrasion
• Eye irritation
• Increased lacrimation
• Eye pruritus
• Ocular discomfort
• Ocular hyperaemia
• Blurred vision
• Iritis
• Reduced visual acuity
• Uveitis
• Endophthalmitis
• Sensation of foreign body
• Vitreous haemorrhage
• Vitritis
• Iridocyclitis
• Conjunctival hyperaemia
• Procedural pain
• Retinal tear
• Rhegmatogenous retinal detachment

Rare

• Traumatic cataract
• Visual acuity reduced transiently

Post marketing experience:

Rare

• Retinal vasculitis
• Retinal occlusive vasculitis

• None known

• Intraocular pressure (IOP) monitoring (IOP elevation should be monitored immediately following the intravitreal injection, appropriate monitoring may consist the below)
  - A check for perfusion of the optic nerve head
  - Tonometry
  - Special precaution is needed in patients with poorly controlled glaucoma (do not inject faricimab while the IOP is ≥30mmHg)
• Ophthalmic examination/ visual outcomes

Additional observations

• Symptoms (Patients should be instructed to report any of the following symptoms)
  - Endophthalmitis (e.g. vision loss, eye pain, redness of the eye, photophobia, blurring of vision)
  - Rhegmatogenous retinal detachment
  - Retinal tear
  - Iatrogenic traumatic cataract
• Intraocular inflammation
  - 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

Faricimab is a humanised bispecific immunoglobulin G1 (IgG1) antibody that acts through inhibition of two distinct pathways by neutralisation of both angiopoietin-2 (Ang-2) and vascular endothelial growth factor A (VEGF-A). Ang-2 causes vascular instability by promoting endothelial destabilisation, pericyte loss, and pathological angiogenesis, thus potentiating vascular leakage and inflammation. It also sensitises blood vessels to the activity of VEGF-A, resulting in further vascular destabilisation. Ang-2 and VEGF-A synergistically increase vascular permeability and stimulate neovascularisation. By dual inhibition of Ang-2 and VEGF-A, faricimab reduces vascular permeability and inflammation, inhibits pathological angiogenesis and restores vascular stability.