Vabysmo

Faricimab.

Clear to opalescent, colourless to brownish-yellow solution, with a pH of 5.5 and an osmolality of 270-370 mOsm/kg.
1 mL solution for injection contains 120 mg of faricimab.
Each vial contains 28.8 mg faricimab in 0.24 mL solution. This provides a usable amount to deliver a single dose of 0.05 mL solution containing 6 mg of faricimab.
Faricimab is a humanised bispecific antibody produced in mammalian Chinese Hamster Ovary (CHO) cell culture by recombinant DNA technology.
Excipients/Inactive Ingredients: L-histidine, Acetic acid 30% (for pH adjustment), L-methionine, Polysorbate 20, Sodium chloride, D-Sucrose, Water for injection.

Pharmacotherapeutic group: Ophthalmologicals, other ocular vascular disorder agents. ATC code: S01LA09.
Pharmacology: Pharmacodynamics: Mechanism of action: 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.
Pharmacodynamic effects: A suppression from baseline of median ocular free Ang-2 and free VEGF-A concentrations was observed from day 7 onwards in the four Phase III studies described hereafter.
nAMD: nAMD is characterised by pathological choroidal neovascularisation (CNV). Leakage of blood and fluid from CNV may cause retinal thickening with sub and/or intraretinal fluid accumulation (SRF, IRF) and haemorrhages, which can result in vision loss.
In TENAYA and LUCERNE, objective, pre-specified visual and anatomic criteria, as well as treating physician clinical assessment, were used to guide treatment decisions at the disease activity assessment time points (week 20 and week 24).
Reductions in mean central subfield thickness (CST) were observed from baseline through to week 48 with Vabysmo, and were comparable to those observed with aflibercept. The mean CST reduction from baseline through the primary endpoint visits (averaged at weeks 40-48) was -137 μm and -137 μm for Vabysmo dosed up to every 16 weeks (Q16W) versus -129 μm and -131 μm with aflibercept, in TENAYA and LUCERNE, respectively.
At Week 48, in both studies there was a comparable effect of Vabysmo and aflibercept on the reduction of IRF, SRF, and pigment epithelial detachment (PED). There were also comparable changes in total CNV lesion area and reductions in CNV leakage area from baseline for patients in the Vabysmo and aflibercept treatment arms.
DMO: DMO is a consequence of DR and is characterised by increased vasopermeability and damage to the retinal capillaries, mediated in part due to VEGF and Ang2, which may result in vision loss.
In YOSEMITE and RHINE, anatomic parameters related to macular oedema were part of the disease activity assessments guiding treatment decisions in the Vabysmo up to Q16W adjustable dosing arm.
The mean CST reduction from baseline at the primary endpoint visits (averaged at weeks 48-56) were numerically greater than those observed with aflibercept, with -207 μm and -197 μm in patients treated with Vabysmo Q8W and Vabysmo up to Q16W adjustable dosing as compared to -170 μm in aflibercept Q8W patients in YOSEMITE; results were 196 μm, 188 μm and 170 μm, respectively in RHINE. Consistent reductions in CST were observed through Year 2.
Greater proportions of patients in both Vabysmo arms achieved absence of IRF and absence of DMO (defined as reaching CST below 325 μm) over time through year 2 as compared to aflibercept in both studies.
Clinical efficacy and safety: nAMD: The safety and efficacy of Vabysmo were assessed in two randomised, multi-centre, double-masked, active comparator-controlled, 2-year studies in patients with nAMD, TENAYA and LUCERNE. A total of 1,329 treatment-naïve patients were enrolled in these and 1,326 patients received at least one dose (664 with Vabysmo). Patient ages ranged from 50 to 99 years with a mean of 75.9 years.
In both studies, patients were randomised in a 1:1 ratio to one of two treatment arms: Vabysmo 6 mg up to Q16W after four initial monthly doses; Aflibercept 2 mg Q8W after three initial monthly doses.
After the first four monthly doses (weeks 0, 4, 8, and 12) patients randomised to the Vabysmo arm received Q16W, every 12 weeks (Q12W) or Q8W dosing based on an assessment of disease activity at weeks 20 and 24, using objective pre-specified ETDRS-measured BCVA and SD-OCT CST criteria as well as treating physician clinical assessment of the presence/absence of macular haemorrhage. Patients remained on these fixed dosing intervals until week 60 without supplemental therapy.
Results: Both studies demonstrated efficacy in the primary endpoint, defined as the mean change from baseline in BCVA when averaged over the week 40, 44, and 48 visits and measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) letter score (Table 1). In both studies, Vabysmo up to Q16W treated patients had a comparable mean change from baseline in BCVA, as the patients treated with aflibercept Q8W. Improvements from baseline BCVA at week 48 are shown in Figure 1 and Figure 2.
The proportion of patients on each of the different treatment intervals at week 48 in TENAYA and LUCERNE respectively was: Q16W, 46% and 45%; Q12W, 34% and 33%; Q8W, 20% and 22%. (See Table 1 and Figures 1 and 2.)

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In both TENAYA and LUCERNE, improvements from baseline in BCVA and CST at week 60 were comparable across the two treatment arms and consistent with those seen at week 48.
Efficacy results in all evaluable subgroups (e.g. age, gender, race, baseline visual acuity, lesion type, lesion size) in each study, and in the pooled analysis, were consistent with the results in the overall populations.
In both studies, Vabysmo up to Q16W demonstrated clinically meaningful improvements from baseline to week 48 in the National Eye Institute Visual Function Questionnaire (NEI VFQ-25) composite score that was comparable to aflibercept Q8W. Patients in Vabysmo arms in TENAYA and LUCERNE achieved a ≥4 point improvement from baseline in the NEI VFQ-25 composite score at week 48.
DMO: The safety and efficacy of Vabysmo were assessed in two randomised, multi-centre, double-masked, active comparator-controlled 2-year studies (YOSEMITE and RHINE) in patients with DMO. A total of 1,891 patients were enrolled in the two studies with 1,622 (85.8%) patients completing the studies through week 100. A total of 1,887 were treated with at least one dose through week 56 (1,262 with Vabysmo). Patient ages ranged from 24 to 91 with a mean of 62.2 years. The overall population included both anti-VEGF naïve patients (78%) and patients who had been previously treated with a VEGF inhibitor prior to study participation (22%). In both studies, patients were randomised in a 1:1:1 ratio to one of the three treatment regimens: Vabysmo 6 mg Q8W after the first 6 monthly doses; Vabysmo 6 mg up to Q16W adjustable dosing administered in 4, 8, 12 or 16-week intervals after the first 4 monthly doses; Aflibercept 2 mg Q8W after the first 5 monthly doses.
In the up to Q16W adjustable dosing arm, the dosing followed a standardised treat-and-extend approach. The interval could be increased in 4-week increments or decreased in 4- or 8-week increments based on CST change as measured on OCT and/or BCVA change as measured by ETDRS letters, using data obtained only at study drug dosing visits.
Results: Both studies demonstrated efficacy in the primary endpoint, defined as the mean change from baseline in BCVA at year 1 (average of the week 48, 52, and 56 visits), measured by the ETDRS Letter Score. In both studies, Vabysmo up to Q16W treated patients had a comparable mean change from baseline in BCVA, as the patients treated with aflibercept Q8W at year 1, and these vision gains were maintained through year 2. Detailed results of both studies are shown in Table 2, Figure 3, and Figure 4 as follows.
After 4 initial monthly doses, the patients in the Vabysmo up to Q16W adjustable dosing arm could have received between the minimum of 6 and the maximum of 21 total injections through week 96. At week 52, 74% and 71% of patients in the Vabysmo up to Q16W adjustable dosing arm achieved a Q16W or Q12W dosing interval in YOSEMITE and RHINE, respectively (53% and 51% on Q16W, 21% and 20% on Q12W). Of these patients, 75% and 84% maintained ≥Q12W dosing without an interval reduction below Q12W through week 96; of the patients on Q16W at week 52, 70% and 82% of patients maintained Q16W dosing without an interval reduction through week 96 in YOSEMITE and RHINE, respectively. At week 96, 78% of patients in the Vabysmo up to Q16W adjustable dosing arm achieved a Q16W or Q12W dosing interval in both studies (60% and 64% on Q16W, 18% and 14% on Q12W). 4% and 6% of patients were extended to Q8W and stayed on ≤Q8W dosing intervals through week 96; 3% and 5% received only Q4W dosing in YOSEMITE and RHINE, respectively. The proportion of patients in YOSEMITE and RHINE, respectively, who received >15 injections in the PTI arms through week 96 was 13% and 18%.
Detailed results from the analyses of YOSEMITE and RHINE studies are listed in Table 2 and Figures 3 and 4 as follows. (See Table 2 and Figures 3 and 4.)

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Efficacy results in patients who were anti-VEGF treatment naïve prior to study participation and in all the other evaluable subgroups (e.g. by age, gender, race, baseline HbA1c, baseline visual acuity) in each study were consistent with the results in the overall populations.
An additional key efficacy outcome in DMO studies was the change in the Early Treatment Diabetic Retinopathy Study Diabetic Retinopathy Severity Scale (ETDRS-DRSS) from baseline to week 52. Of the 1,891 patients enrolled in Studies YOSEMITE and RHINE, 708 and 720 patients were evaluable for DR endpoints.
The ETDRS-DRSS scores ranged from 10 to 71 at baseline.
The majority of patients, approximately 60%, had moderate to severe nonproliferative DR (DRSS 43/47/53) at baseline.
At week 52, the proportion of patients improving by ≥2 steps on the ETDRS-DRSS was 43% to 46% across the Vabysmo Q8W and Vabysmo adjustable up to Q16W arms in both studies, compared to 36% and 47% in aflibercept Q8W arms of YOSEMITE and RHINE, respectively. The results at week 96 were 43% to 54% across the Vabysmo Q8W and Vabysmo adjustable up to Q16W arms in both studies, compared to 42% and 44% in aflibercept Q8W arms of YOSEMITE and RHINE, respectively. Comparable results across the treatment arms were observed in both studies in the proportions of patients improving by ≥3 steps on the ETDRS-DRSS from baseline at week 52, and these results were maintained at week 96.
The results from the ≥2-step and ≥3-step ETDRS-DRSS improvement analyses from baseline at week 52 and at week 96 are shown in Table 3 as follows. Clinically meaningful proportions of patients achieved ≥2-step DRSS improvement from baseline at Week 52 in all three treatment arms (faricimab Q8W, faricimab PTI and aflibercept Q8W), and these outcomes were maintained at Week 96. (See Table 3.)

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Across studies, Vabysmo Q8W and up to Q16W adjustable dosing showed improvements in the pre-specified efficacy endpoint of mean change from baseline to week 52 in the NEI VFQ-25 composite score that were comparable to aflibercept Q8W and exceeded the threshold of 4 points. Vabysmo Q8W and up to Q16W adjustable dosing also demonstrated clinically meaningful improvements in the prespecified efficacy endpoint of change from baseline to week 52 in the NEI VFQ-25 near activities, distance activities, and driving scores, that were comparable to aflibercept Q8W. The magnitude of these changes corresponds to a 15-letter gain in BCVA. Comparable proportions of patients treated with Vabysmo Q8W, Vabysmo up to Q16W adjustable dosing, and aflibercept Q8W experienced a clinically meaningful improvement of ≥4-points from baseline to week 52 in the NEI VFQ-25 composite score, a pre-specified efficacy endpoint. These results were maintained at week 100.
DR treatment effects in the subgroup of patients who were anti-VEGF naïve prior to study participation were comparable to those observed in the overall DR evaluable population. Treatment effects in evaluable subgroups (e.g. by age, gender, race, baseline HbA1c, and baseline visual acuity) in each study were generally consistent with the results in the overall population.
Pharmacokinetics: Vabysmo is administered intravitreally (IVT) to exert local effects in the eye.
Absorption and Distribution: Based on a population pharmacokinetic analysis (including nAMD and DMO N = 2,246), maximum free (unbound to VEGF-A and Ang-2) faricimab plasma concentrations (Cmax) are estimated to occur approximately 2 days post-dose. Mean (±SD [standard deviation]) plasma Cmax are estimated 0.23 (0.07) μg/mL and 0.22 (0.07) μg/mL respectively in nAMD and in DMO patients. After repeated administrations, mean plasma free faricimab trough concentrations are predicted to be 0.002-0.003 μg/mL for Q8W dosing.
Faricimab exhibited dose-proportional pharmacokinetics (based on Cmax and AUC) over the dose range 0.5 mg-6 mg. No accumulation of faricimab was apparent in the vitreous or in plasma following monthly dosing.
Maximum plasma free faricimab concentrations are predicted to be approximately 600 and 6000-fold lower than in aqueous and vitreous humour respectively and below the binding affinity for VEGF and Ang-2. Therefore, systemic pharmacodynamics effects are unlikely, further supported by the absence of significant changes in free VEGF and Ang-2 concentration in plasma upon faricimab treatment in clinical studies.
Population pharmacokinetic analysis has shown an effect of age and body weight on ocular or systemic pharmacokinetics of faricimab respectively. Both effects were considered not clinically meaningful; no dose adjustment is needed.
Biotransformation and Elimination: Faricimab is a protein-based therapeutic hence its metabolism and elimination have not been fully characterised. Faricimab is expected to be catabolized in lysosomes to small peptides and amino acids, which may be excreted renally, in a similar manner to the elimination of endogenous IgG.
The faricimab plasma concentration-time profile declined in parallel with the vitreous and aqueous concentration-time profiles. The estimated mean ocular half-life and apparent systemic half-life of faricimab is 7.5 days.
Special populations: Elderly: In the four Phase III clinical studies, approximately 60% (1,149/1,929) of patients randomised to treatment with Vabysmo were ≥65 years of age. Population pharmacokinetic analysis has shown an effect of age on ocular pharmacokinetics of faricimab, which was not considered clinically meaningful. No dose adjustment is required in patients 65 years and above.
Renal impairment: No specific studies in patients with renal impairment have been conducted with Vabysmo. Pharmacokinetic analysis of patients in all Phase III clinical studies of which 64% had renal impairment (mild 38%, moderate 24%, and severe 2%), revealed no differences with respect to systemic pharmacokinetics of faricimab after intravitreal administration of Vabysmo. No dose adjustment is required in patients with renal impairment.
Hepatic impairment: No specific studies in patients with hepatic impairment have been conducted with Vabysmo. However, no special considerations are needed in this population because metabolism occurs via proteolysis and does not depend on hepatic function. No dose adjustment is required in patients with hepatic impairment.
Other special populations: The systemic pharmacokinetics of faricimab are not influenced by race. Gender was not shown to have a clinically relevant influence on systemic pharmacokinetics of faricimab. No dose adjustment is needed.
Toxicology: Preclinical safety data: No studies have been conducted on the carcinogenic or mutagenic potential of Vabysmo.
In pregnant cynomolgus monkeys, IV injections of Vabysmo resulting in serum exposure (Cmax) more than 500-times the maximum human exposure did not elicit developmental toxicity or teratogenicity, and had no effect on weight or structure of the placenta, although, based on its pharmacological effect Vabysmo should be regarded as potentially teratogenic and embryo-/foetotoxic.
Systemic exposure after ocular administration of Vabysmo is very low.

Vabysmo is indicated for the treatment of adult patients with: neovascular (wet) age-related macular degeneration (nAMD) (see Pharmacology: Pharmacodynamics under Actions); visual impairment due to diabetic macular oedema (DMO) (see Pharmacology: Pharmacodynamics under Actions).

Vabysmo must be administered by a qualified healthcare professional trained in intravitreal injections. Each vial should only be used for the treatment of a single eye.
Posology: nAMD: The recommended dose for Vabysmo is 6 mg (0.05 mL solution) administered by intravitreal injection every 4 weeks for the first 4 doses.
Thereafter, an assessment of disease activity based on anatomic and/or visual outcomes is recommended 20 and/or 24 weeks after treatment initiation so treatment can be individualised. In patients without disease activity, administration of Vabysmo every 16 weeks should be considered. In patients with disease activity, treatment every 8 weeks or 12 weeks should be considered.
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.
DMO: The recommended dose for Vabysmo is 6 mg (0.05 mL solution) administered by intravitreal injection every 4 weeks for the first 4 doses.
Thereafter, treatment may be individualised using a treat-and-extend approach following an assessment of the individual patient's anatomic and visual outcomes. The dosing interval may be extended from every 4 to every 16 weeks, with extensions in increments of up to 4 weeks, based on the physician's judgement of the individual patient's anatomic and/or visual outcomes. If anatomic and/or visual outcomes change, the treatment interval should be adjusted accordingly, and interval reductions of up to 8 weeks may be implemented if deemed necessary (see Pharmacology: Pharmacodynamics under Actions).
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.
Duration of treatment: Vabysmo is intended for long-term treatment.
If visual and/or anatomic outcomes indicate that the patient is not benefitting from continued treatment, Vabysmo should be discontinued.
Delayed or missed dose: If a dose is delayed or missed, the patient should return for assessment at the next available visit and continue dosing depending on physician's discretion.
Special populations: Elderly (≥65 years): No dose adjustment is required in patients aged 65 years or above (see Pharmacology: Pharmacokinetics under Actions).
Renal impairment: No dose adjustment is required in patients with renal impairment (see Pharmacology: Pharmacokinetics under Actions).
Hepatic impairment: No specific studies in patients with hepatic impairment have been conducted with Vabysmo. No dose adjustment is required in patients with hepatic impairment (see Pharmacology: Pharmacokinetics under Actions).
Paediatric population: The safety and efficacy of Vabysmo in children and adolescents have not been established. No data are available.
Method of administration: Single-use vial for intravitreal use only.
Vabysmo should be inspected visually for particulate matter and discolouration prior to administration, and if present, the vial should not be used.
The intravitreal injection procedure should be carried out under aseptic conditions, which includes the use of surgical hand disinfection, sterile gloves, a sterile drape and a sterile eyelid speculum (or equivalent). The patient's medical history for hypersensitivity reactions should be carefully evaluated prior to performing the intravitreal procedure (see Adverse Reactions). Adequate anaesthesia and a broad-spectrum topical microbicide to disinfect the periocular skin, eyelid and ocular surface should be administered prior to the injection.
The injection needle should be inserted 3.5 to 4.0 mm posterior to the limbus into the vitreous cavity, avoiding the horizontal meridian and aiming towards the centre of the globe. The injection volume of 0.05 mL is then delivered slowly; a different scleral site should be used for subsequent injections.
After injection, any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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. Sterile equipment should be available in case paracentesis is required.
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 instructions on handling of the medicinal product before administration, see Special precautions for disposal under Cautions for Usage.

Overdosing with greater than recommended injection volume may increase intraocular pressure. In the event of overdose, IOP should be monitored and, if deemed necessary by the treating physician, appropriate treatment should be initiated.

Ocular or periocular infections.
Active intraocular inflammation.
Hypersensitivity to the active substance or to any of the excipients listed in Description.

Traceability: In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
Intravitreal injection-related reactions: Intravitreal injections, including those with Vabysmo have been associated with endophthalmitis, intraocular inflammation, rhegmatogenous retinal detachment and retinal tear (see Adverse Reactions). 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 previously mentioned events without delay, to permit prompt and appropriate management.
Intraocular pressure increases: Transient increases in intraocular pressure (IOP) have been seen within 60 minutes of intravitreal injection, including those with Vabysmo (see Adverse Reactions). Sustained (present at 2 or more consecutive visits) IOP increases >21 mmHg have also been reported. 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.
Vabysmo has not been studied in patients with poorly controlled glaucoma. Special precaution is needed in patients with poorly controlled glaucoma.
Systemic effects: Arterial thromboembolic events (ATEs): Systemic adverse events including arterial thromboembolic events have been reported following intravitreal injection of vascular endothelial growth factor (VEGF) inhibitors, including Vabysmo, and there is a theoretical risk that these may be related to VEGF inhibition.
There is limited data on the safety of Vabysmo in patients with history of stroke or transient ischemic attack or myocardial infarction.
Immunogenicity: As this is a therapeutic protein, there is a potential for immunogenicity with Vabysmo (see Adverse Reactions). 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 (see Adverse Reactions).
Bilateral treatment: The safety and efficacy of Vabysmo administered in both eyes concurrently have not been studied.
Concomitant use of other anti-VEGF: There are no data available on the concomitant use of Vabysmo with anti-VEGF medicinal products or other therapies (e.g., photodynamic therapy) for the treatment of nAMD or DMO in the same eye. Vabysmo 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); 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: 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 Vabysmo therapy, caution should be used in patients with these risk factors for retinal pigment epithelial tears.
Populations with limited data: In nAMD clinical trials, there is limited data on patients with a total lesion size >9 disc areas on fundus fluorescein angiography. There is only limited experience in the treatment of DMO patients with HbA1c over 10%, patients with high-risk proliferative diabetic retinopathy (DR), or nAMD and DMO patients with active systemic infections. There is also no experience of treatment with Vabysmo in diabetic patients with uncontrolled hypertension.
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".
Effects on ability to drive and use machines: Vabysmo 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.

Women of childbearing potential: Female patients of childbearing potential should use effective contraception during treatment with Vabysmo and for at least 3 months following the last intravitreal injection of Vabysmo.
Pregnancy: There are no or limited amount of data from the use of faricimab in pregnant women. Systemic exposure after ocular administration of Vabysmo is very low. Animal studies in pregnant cynomolgus monkeys did not indicate direct or indirect harmful effects with respect to reproductive toxicity including embryo-foetal development (see Pharmacology: Toxicology: Preclinical safety data under Actions).
As a precautionary measure it is preferable to avoid the use of Vabysmo 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 is not recommended during breast-feeding. A decision must be made whether to discontinue breastfeeding or to discontinue/abstain from Vabysmo 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 Pharmacology: Toxicology: Preclinical safety data under Actions).

Summary of the safety profile: Based on Phase III studies, the most frequently reported adverse reactions were cataract (10.7%), conjunctival haemorrhage (7.3%), vitreous floaters (3.6%), IOP increased (3.6%), retinal pigment epithelial tear (nAMD only) (2.9%), and eye pain (2.5%).
The most serious adverse reactions were cataract (0.9%), uveitis (0.5%), vitritis (0.3%), endophthalmitis (0.3%), retinal tear (0.2%), rhegmatogenous retinal detachment (<0.1%) (see Precautions).
Tabulated list of adverse reactions: The adverse reactions 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). Within each frequency grouping, adverse drug reactions are presented in order of decreasing seriousness. (See Table 4.)

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Description of selected adverse reactions: 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 Vabysmo clinical trials in patients with nAMD and DMO. Across indications, no notable difference between the groups treated with Vabysmo and the comparator were observed.
Immunogenicity: There is a potential for an immune response in patients treated with Vabysmo (see Precautions). After dosing with Vabysmo for up to 48 (nAMD) and 100 (DMO) weeks, treatment-emergent anti-faricimab antibodies were detected in approximately 10% of patients. The clinical significance of anti-faricimab antibodies on safety is unclear at this time. Among the patients with anti-faricimab antibodies a higher incidence of intraocular inflammation adverse reactions were observed however the overall incidence of anti-faricimab antibody positivity and intraocular inflammation in the entire trial population is approximately 1%. Anti-faricimab antibodies were not associated with an impact on clinical efficacy or systemic pharmacokinetics.
Retinal pigment epithelial tear: Retinal pigment epithelial (RPE) tear is a complication of pigment epithelial detachment (PED) in patients with nAMD. RPE tears are common in nAMD patients with PED, treated with IVT anti-VEGF agents including faricimab. There was a higher rate of RPE tear in the faricimab group (2.9%) compared to aflibercept group (1.4%). The majority of events were mild to moderate, without impact to vision and occurred during the loading phase.
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.

No studies evaluating the drug interaction potential of Vabysmo have been performed.

Special precautions for disposal: Do not shake.
The vial contains more than the recommended dose of 6 mg. The fill volume of the vial (0.24 mL) is not to be used in total. The excess volume should be expelled prior to injection. Injecting the entire volume of the vial results in overdose. The injection dose must be set to the 0.05 mL dose mark, i.e. 6 mg faricimab.
Vabysmo should be inspected visually upon removal from the refrigerator and prior to administration. If particulates or cloudiness are visible, the vial must not be used. The contents of the vial and the transfer filter needle are sterile and for single use only. Do not use if the packaging, vial and/or transfer filter needle are damaged or expired. Detailed instructions for use are provided in Instructions for use of vial as follows.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Instructions for use of vial: 1. Gather the following supplies: One Vabysmo vial (included); One sterile 5-micron blunt transfer filter needle 18-gauge x 1½ inch, 1.2 mm x 40 mm (included); One sterile 1 mL Luer lock syringe with a 0.05 mL dose mark (not included); One sterile injection needle 30-gauge x ½ inch (not included); Alcohol swab (not included). Note that a 30-gauge injection needle is recommended to avoid increased injection forces that could be experienced with smaller diameter needles.
2. To ensure all liquid settles at the bottom of the vial, place the vial upright on a flat surface (for about 1 minute) after removal from packaging. Gently tap the vial with the finger, as liquid may stick to the top of the vial.
3. Remove the flip-off cap from the vial and wipe the vial septum with an alcohol swab.
4. Aseptically and firmly attach the included 18-gauge x 1½ inch transfer filter needle onto a 1 mL Luer lock syringe.
5. Using aseptic technique, push the transfer filter needle into the center of the vial septum, push it all the way in, then tilt the vial slightly so that the needle touches the bottom edge of the vial.
6. Hold the vial slightly inclined and slowly withdraw all the liquid from the vial. Keep the bevel of the transfer filter needle submerged in the liquid, to avoid introduction of air.
7. Ensure that the plunger rod is drawn sufficiently back when emptying the vial, in order to completely empty the transfer filter needle.
8. Disconnect the transfer filter needle from the syringe and dispose of it in accordance with local regulations. Do not use the transfer filter needle for the intravitreal injection.
9. Aseptically and firmly attach a 30-gauge x ½ inch injection needle onto the Luer lock syringe.
10. Carefully remove the plastic needle shield from the needle by pulling it straight off.
11. To check for air bubbles, hold the syringe with the needle pointing up. If there are any air bubbles, gently tap the syringe with the finger until the bubbles rise to the top.
12. Carefully expel the air from the syringe and needle, and slowly depress the plunger to align the rubber stopper tip to the 0.05 mL dose mark. The syringe is ready for the injection. Ensure that the injection is given immediately after preparation of the dose.
13. Inject slowly until the rubber stopper reaches the end of the syringe to deliver the volume of 0.05 mL. Confirm delivery of the full dose by checking that the rubber stopper has reached the end of the syringe barrel. Any waste material or unused medicinal product should be disposed of in accordance with local regulations.
Incompatibilities: In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

Store Vabysmo in the refrigerator between 2°C to 8°C.
Do not freeze.
Keep the vial in the original carton to protect from light.
Prior to use, the unopened vial may be kept at room temperature, 20°C to 25°C, for up to 24 hours.
Ensure that the injection is given immediately after preparation of the dose.
Shelf life: 30 months.

Other Eye Preparations

S01LA09 - faricimab ; Belongs to the class antineovasculatisation agents. Used in the management of neovascular macular degeneration.

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