Vabysmo

Active ingredient(s): Faricimab (genetically produced in CHO [Chinese Hamster Ovary] cells).
Faricimab (Vabysmo) for injection is a clear to opalescent, colorless to brownish-yellow solution in a single-dose glass vial, containing 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.
One single-dose (0.05 mL solution for injection) contains 0.028 mg sodium.
Sterile/Radioactive Statement: Sterile product.
Excipients/Inactive Ingredients: L-histidine, Acetic Acid, L-methionine, Polysorbate 20 (manufactured from genetically modified maize), Sodium Chloride, D-Sucrose (manufactured from genetically modified sugar beet), Water for Injection.

Pharmacotherapeutic group: Ophthalmologicals/Other ocular vascular disorder agents. ATC code: S01LA09.
Pharmacology: Pharmacodynamics: Mechanism of Action: Faricimab is a humanized bispecific immunoglobulin G1 (IgG1) antibody that acts through inhibition of two distinct pathways by neutralization of both Ang-2 and vascular endothelial growth factor A (VEGF-A). Ang-2 causes vascular instability by promoting endothelial destabilization, pericyte loss, and pathological angiogenesis, thus potentiating vascular leakage and inflammation. It also sensitizes blood vessels to the activity of VEGF-A resulting in further vascular destabilization. Ang-2 and VEGF-A synergistically increase vascular permeability and stimulate neovascularization. By dual inhibition of Ang-2 and VEGF-A, faricimab reduces vascular permeability and inflammation, inhibits pathological angiogenesis and restores vascular stability.
Pharmacodynamics: In the six phase III studies described in the following, a suppression in the median ocular concentrations of free Ang-2 and free VEGF-A was detected from Day 7 compared to baseline.
nAMD: Similar reductions in the mean thickness of the central region of the fovea (central subfield thickness, CST) to those for aflibercept were observed from baseline through week 48 with Faricimab (Vabysmo). The mean CST reduction from baseline to the primary endpoint visits (mean at weeks 40, 44 and 48) was -137 μm and -137 μm for Faricimab (Vabysmo) dosed at intervals of 8 weeks (q8w), 12 weeks (q12w) or 16 weeks (q16w) versus -129 μm and -131 μm with the use of aflibercept in the TENAYA and LUCERNE studies, respectively. These mean CST reductions were maintained throughout year 2. Faricimab (Vabysmo) and aflibercept had a comparable effect on the reduction of intraretinal fluid (IRF), subretinal fluid (SRF), and pigment epithelial detachment (PED). At the primary endpoint visits, the proportion of patients in the TENAYA and LUCERNE studies, respectively, without IRF was 76%-82% and 78%-85 % under treatment with Faricimab (Vabysmo) vs. 74%-85% and 78%-84% under treatment with aflibercept. The percentage of patients without SRF in the two studies was 70%-79% and 66%-78% under treatment with Faricimab (Vabysmo) vs. 66%-78% and 62%-76% under treatment with aflibercept. The percentage of patients without PED in the two studies was 3%-8% and 3%-6% under treatment with Faricimab (Vabysmo) vs. 8%-10% and 7%-9% under treatment with aflibercept. These reductions in IRF, SRF and PED were maintained in year 2 (weeks 104-108).
Comparable changes from baseline in the total area of lesions due to choroidal neovascularisation (CNV) and comparable reductions in CNV leakage area with excretion of blood and fluid were observed in both studies for patients under treatment with Faricimab (Vabysmo) and aflibercept at week 48.
DME: Reductions in mean CST from baseline observed in both the YOSEMITE study and the RHINE study were numerically greater in patients treated with Faricimab (Vabysmo) every 8 weeks (q8w) and Faricimab (Vabysmo) up to q16w adjustable dosing as compared to aflibercept q8w from week 4 to week 100. Greater proportions of patients in both Faricimab (Vabysmo) arms achieved absence of IRF and absence of DME (defined as reaching CST below 325 μm on OCT) over time in both studies, compared to the aflibercept arm. Comparable reductions in SRF were observed across the respective Faricimab (Vabysmo) and aflibercept treatment arms over time in both studies. The mean reduction of CST from baseline to the primary endpoint visits (averaged at weeks 48, 52 and 56) in the YOSEMITE study was 207 μm and 197 μm in patients treated with Faricimab (Vabysmo) q8w and Faricimab (Vabysmo) up to q16w adjustable dosing compared to 170 μm in patients treated with aflibercept q8w; results were 196 μm, 188 μm and 170 μm, respectively in the RHINE study. These mean CST reductions were maintained through year 2. The proportions of patients with absence of DME at primary endpoint visits (min-max) in the YOSEMITE study were 77%-87% and 80%-82% in patients treated with Faricimab (Vabysmo) q8w and Faricimab (Vabysmo) up to q16w adjustable dosing, respectively, as compared to 64%-71% in patients treated with aflibercept q8w; results were 85%-90%, 83%-87%, and 71%-77%, respectively in the RHINE study. These results were maintained through year 2.
In the YOSEMITE study, the proportions of patients with absence of IRF at primary endpoint visits (averaged at weeks 48, 52 and 56) were 42%-48% and 34%-43% in patients treated with Faricimab (Vabysmo) q8w and Faricimab (Vabysmo) up to q16w adjustable dosing, respectively, as compared to 22%-25% in patients treated with aflibercept q8w; results were 39%-43%, 33%-41%, and 23%-29%, respectively in the RHINE study. These results were maintained through year 2.
BRVO and CRVO: In phase III studies in patients with branch retinal vein occlusion (BRVO; BALATON) and central/hemiretinal vein occlusion (C/HRVO; COMINO), reductions in mean CST were observed from baseline to week 24 with Faricimab (Vabysmo) every 4 weeks (q4w) and were comparable to those seen with aflibercept q4w. The mean CST reduction from baseline to week 24 was 311.4 μm for Faricimab (Vabysmo) q4w versus 304.4 μm for aflibercept q4w, and 461.6 μm for Faricimab (Vabysmo) q4w versus 448.8 μm for aflibercept q4w, in BALATON and COMINO, respectively. CST reductions were maintained through week 72 when patients moved to a Vabysmo up to q16w adjustable dosing regimen.
Comparable proportions of patients in both Faricimab (Vabysmo) and aflibercept arms achieved absence of IRF, absence of SRF and absence of macular edema (defined as reaching CST below 325 μm) over time through week 24, in both studies. These results were maintained through week 72 when patients moved to a Faricimab (Vabysmo) up to q16w adjustable dosing regimen.
In BALATON, at week 24, the proportion of patients with absence of macular edema was 95.3% in patients treated with Faricimab (Vabysmo) q4w versus 93.9% in patients treated with aflibercept q4w; the proportion of patients with absence of IRF was 72.5% in patients treated with Faricimab (Vabysmo) q4w versus 66% in patients treated with aflibercept q4w. The proportion of patients with absence of SRF was 91.3% in patients in the Faricimab (Vabysmo) q4w arm, versus 90.3% in patients in the aflibercept q4w arm.
In COMINO, at week 24, the proportion of patients with absence of macular edema was 93.7% in patients treated with Faricimab (Vabysmo) q4w versus 92% in patients treated with aflibercept q4w. The proportion of patients with absence of IRF was 76.2% in patients treated with Faricimab (Vabysmo) q4w versus 70.8% in patients treated with aflibercept q4w; the proportion of patients with absence of SRF was 96.4% in patients treated with Faricimab (Vabysmo) q4w versus 93.4% in patients treated with aflibercept q4w.
Clinical/Efficacy Studies: Treatment of neovascular (wet) age-related macular degeneration (nAMD): The safety and efficacy of faricimab were evaluated in two 2-arm, randomized (1:1), multicentre, double-masked studies (TENAYA and LUCERNE) in patients with nAMD compared to anti-VEGF treatment. Treatment (faricimab 6 mg or aflibercept 2 mg) was administered by intravitreal injection, initially at 4-week intervals. In the aflibercept arm, the dosing interval after 3 initial aflibercept injections was 8 weeks for the remainder of the study (q8w). In the faricimab arm, the dosing interval was individually adjusted after 4 initial doses. The final (fixed) dosing interval was 8 weeks (q8w), 12 weeks (q12w) or a maximum of 16 weeks (q16w) depending on the change in CST measured using SD-OCT and/or BCVA change measured based on ETDRS letter scores, both defined in the protocol, as well as the treating physician's clinical assessment of the presence/absence of macular hemorrhage at weeks 20 and 24. From week 60 onwards, patients in the Faricimab (Vabysmo) arm were moved to an adjustable dosing regimen, where the dosing interval could be increased by up to 4-week increments (up to q16w) or could be decreased by up to 8 week increments (up to q8w) based on an automated objective assessment of pre-specified visual and anatomical disease activity criteria. Patients in the aflibercept arm remained on q8w dosing throughout the entire study period. Both studies were 112 weeks in duration.
The trials included a total of 1,329 treatment-naïve patients, of whom 1,135 (85%) patients completing the studies through week 112. A total of 1,326 received at least one dose (including 664 patients in the faricimab arm). The average age [age range] of the population that was investigated was 75.9 years [50 to 99 years]. The primary efficacy endpoint was the mean change from the baseline in BCVA within the first year (based on the mean over weeks 40, 44 and 48), determined using the Early Treatment Diabetic Retinopathy Study (ETDRS) letter chart at a distance of 4 metres. In both studies, the primary hypothesis (non-inferiority) was confirmed: Patients treated with Faricimab (Vabysmo) at an interval of up to q16w and patients treated with aflibercept q8w exhibited a comparable mean change from their respective baseline at year 1. Meaningful vision gains from baseline were seen through week 112 in both treatment arms. Detailed results for both studies are shown in Tables 1 and 2, as well as in Figure 1 as follows.
The proportion of patients in the personalized treatment interval groups at week 48 in the TENAYA and LUCERNE studies, respectively was: q16w: 46%, 45%; q12w: 34%, 33%; q8w: 20%, 22%.
The proportion of patients in the personalised treatment interval groups at week 112 in the TENAYA and LUCERNE, respectively, was: q16w: 59%, 67%; q12w: 15%, 14%; q8w: 26%, 19%. (See Tables 1, 2 and Figure 1.)

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In both the TENAYA and LUCERNE studies, 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 outcomes in all evaluable subgroups (e.g. according to age, gender, ethnic origin, baseline visual acuity, lesion type, lesion size) in each study, and in the pooled analysis, were consistent with the outcomes in the overall populations.
In both studies, Faricimab (Vabysmo) administered at intervals of 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 were comparable to those for aflibercept q8w. Patients in Faricimab (Vabysmo) arms in the TENAYA and LUCERNE studies achieved a ≥4-point improvement from baseline in the NEI VFQ-25 composite score at week 48. This improvement persisted until week 112.
Treatment of diabetic macular edema (DME): The safety and efficacy of faricimab were evaluated in two 3-arm, randomized (1:1:1), multicentre, double-masked studies (YOSEMITE and RHINE) conducted over a period of 2 years in patients with DME in comparison to anti-VEGF treatment. Patients in the three study arms received intravitreal injections of 6 mg faricimab q8w (after 6 monthly injections at the start of the treatment), 6 mg faricimab with a personalised injection interval up to a maximum of q16w (after 4 monthly injections at the start of the treatment or 2 mg aflibercept q8w (after 5 monthly injections at the start of the treatment). In the faricimab arm with extended dosing up to q16w, dosing followed a standardized treat-and-extend approach. Based on changes in CST as measured using OCT and/or changes in BCVA change as measured with the ETDRS letter score, the personalised injection interval in the faricimab group could be extended by 4 weeks or shortened by 4 or 8 weeks at each of the study drug dosing visits (see Dosage & Administration).
The trials included a total of 1,891 patients (of whom approximately 94% had type 2 diabetes mellitus), 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 Faricimab (Vabysmo)). The mean age [age range] of the patients studied was 62.2 years [24 to 91 years]. The study population included both anti-VEGF naïve patients (78%) and patients who had undergone previous anti-VEGF therapy (22%).
The primary efficacy endpoint was the mean change in BCVA from baseline to the end of the first year (mean at weeks 48, 52 and 56) determined using the Early Treatment Diabetic Retinopathy Study (ETDRS) letter chart at a distance of 4 metres. In both studies, the primary hypothesis (noninferiority) was confirmed for both treatment arms: patients treated with Faricimab (Vabysmo) q8w or patients treated with Faricimab (Vabysmo) on extended dosing up to q16w and patients treated with aflibercept q8w exhibited a comparable mean change from their respective baselines in BCVA at year 1, and these vision gains were maintained through year 2.
After 4 initial monthly doses, the patients in the Faricimab (Vabysmo) arm with up to q16w adjustable dosing interval could have received a total of at least 6 and a maximum of 21 injections through week 96. At week 52, 74% and 71%, respectively of patients in the respective Faricimab (Vabysmo) arms with up to q16w adjustable dosing in the YOSEMITE and RHINE studies achieved a dosing interval of q16w or q12w (53% and 51% on q16w, 21% and 20% on q12w). Of these patients in the YOSEMITE and RHINE studies, respectively, 75% and 84% maintained ≥q12w dosing without an interval reduction to 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. At week 96, 78% of patients in the respective Faricimab (Vabysmo) arm with up to q16w adjustable dosing achieved a q16w or q12w dosing interval in both studies (60% and 65% on q16w, 18% and 14% on q12w). In 4% and 6% of patients in the YOSEMITE and RHINE studies, respectively, the interval was extended to q8w and the patients maintained a dosing interval of ≤q8w through week 96; 3% and 5% were only given a q4w interval up to the end of week 96.
Detailed results from the analyses of the YOSEMITE and RHINE studies are given in Tables 3, 4, 5, 6 and in Figure 2 as follows. (See Tables 3, 4, 5, 6 and Figure 2.)

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Efficacy outcomes in patients who were anti-VEGF treatment naive prior to study participation and in all the other evaluable subgroups (e.g. according to age, gender, ethnic origin, baseline HbA1c, baseline visual acuity) in each study were consistent with the outcomes in the respective overall populations.
The treatment effect was independent of glycemic management, and comparable outcomes were achieved with faricimab treatment in patients whose HbA1c improved or worsened by >0.5% over time, or remained within 0.5% of baseline.
Treatment of Macular Edema Secondary to BRVO and CRVO: The safety and efficacy of faricimab was investigated in two multicentre studies in patients with macular oedema resulting from BRVO (BALATON) or C/HRVO (COMINO). Both studies consisted of an initial 24-week, randomized (1:1), actively controlled (aflibercept) treatment phase. After this, all patients (including those originally treated with aflibercept) were treated with faricimab based on an individually tailored dosage regimen up to week 68 (last visit in week 72). The dosing interval could be extended by 4 weeks up to a maximum of q16w and then shortened again by 4, 8 or 12 weeks, if necessary (deterioration in CST and/or visual acuity), based on disease activity (assessed using an automated objective evaluation of criteria relating to vision and anatomical criteria defined beforehand). The treatment interval was not extended again after stabilisation of disease activity in patients who required a shortening of the interval. This excluded patients with a minimum (4-week) interval between injections.
A total of 1282 patients (553 in BALATON and 729 in COMINO) were enrolled in the two studies, with 1,276 patients treated with at least one dose through week 24 (641 with Faricimab (Vabysmo)).
Both studies showed efficacy in the primary endpoint, defined as the change from baseline in BCVA at week 24, as measured by the ETDRS Letter Score. In both studies, Faricimab (Vabysmo) q4w treated patients had a non-inferior mean change from baseline in BCVA at week 24, compared to patients treated with aflibercept q4w and these vision gains were maintained through week 72 when patients moved to a Vabysmo up to q16w adjustable dosing regimen.
Between week 24 and week 68, 81.5% and 74.0% of the patients receiving Faricimab (Vabysmo) 6 mg up to q16w adjustable dosing regimen achieved a q16w or q12w dosing interval in BALATON and COMINO, respectively. Of these patients, 72.1% and 61.6% completed at least one cycle of q12w, and maintained q16w or q12w dosing interval without an interval reduction below q12w through week 68 in BALATON and COMINO, respectively; 1.2% and 2.5% of the patients received only q4w dosing through week 68 in BALATON and COMINO, respectively.
Detailed results of both studies are shown in Table 7 and 8, Figure 3 and Figure 4 as follows. (See Tables 7 and 8, Figures 3 and 4.)

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Immunogenicity: There is a potential for an immune response in patients treated with Faricimab (Vabysmo) (see Precautions).
After dosing with Faricimab (Vabysmo) for up to 112 (nAMD), 100 (DME) and 72 (BRVO/CRVO) weeks, treatment-emergent anti-faricimab antibodies were detected in approximately 13.8%, 9.6% and 14.4% of patients with nAMD, DME, and BRVO/ CRVO randomized to faricimab, respectively. The clinical significance of anti-faricimab antibodies regarding safety is unclear at this time. Among patients with anti-faricimab antibodies, a higher incidence of adverse reactions with intraocular inflammation was observed. However, the overall incidence of anti-faricimab antibody positivity and intraocular inflammation in the entire study population is approximately 1%. Anti-faricimab antibodies were not associated with an impact on clinical efficacy or systemic pharmacokinetics.
Pharmacokinetics: Absorption: Faricimab (Vabysmo) is administered intravitreally (IVT) to exert local effects in the eye. There have been no clinical studies performed with other routes of administration.
Based on a population pharmacokinetic analysis (including nAMD and DME N=2,246), maximum free (unbound to VEGF-A and Ang-2) faricimab plasma concentrations (C_max) are estimated to occur approximately 2 days post-dose. Mean (±SD) plasma C_max are estimated 0.23 (0.07) μg/mL and 0.22 (0.07) μg/mL respectively in nAMD and in DME patients. After repeated administrations, mean free plasma faricimab trough concentrations are predicted to be 0.002-0.003 μg/mL for Q8W dosing.
Faricimab exhibited dose-proportional pharmacokinetics (based on C_max and AUC) over the dose range 0.5 mg-6 mg. There was no accumulation of faricimab in the vitreous body or in plasma following monthly dosing based on exposure estimates from the population pharmacokinetic model.
Pharmacokinetic analysis of patients with nAMD, DME, BRVO and CRVO (N=2,977) has shown that the pharmacokinetics of faricimab are comparable in these patients.
Distribution: No information.
Metabolism: The metabolism of faricimab has not been studied directly. Faricimab is assumed to be catabolised into small peptides and amino acids in lysosymes, similar to endogenous lgG molecules.
Elimination: The faricimab plasma concentration-time profile declined in parallel with the concentration-time profiles in the vitreous body and intraocular fluid. The estimated mean ocular half-life and apparent systemic half-life of faricimab are each approximately 7.5 days.
Pharmacokinetics in Special Populations: Pediatric Population: The safety and efficacy of Faricimab (Vabysmo) in pediatric patients have not been established.
Geriatric Population: In the six phase III clinical studies, approximately 58% (1,496/2,571) of patients randomized to treatment with Faricimab (Vabysmo) were aged ≥65 years. Population pharmacokinetic analysis has shown an effect of age on the ocular pharmacokinetics of faricimab, which was not considered clinically meaningful (see Special Dosage Instructions under Dosage & Administration and Use in the Elderly under Precautions).
Renal impairment: No formal pharmacokinetic study has been conducted in patients with renal impairment. Pharmacokinetic analysis of patients in all clinical studies including 1,115 patients with mild, 669 with moderate and 54 with severe renal function disorder revealed no differences with respect to systemic pharmacokinetics of faricimab after intravitreal administration of Faricimab (Vabysmo).
Hepatic impairment: No formal pharmacokinetic study has been conducted in patients with hepatic impairment.
Other demographic factors: The population pharmacokinetic analysis revealed an effect of body weight on the ocular and systemic pharmacokinetics of faricimab. This effect was not considered clinically meaningful, such that, no dose adjustment is required.
A population-kinetic analysis provides no indication for any influences on the systemic pharmacokinetics of Faricimab (Vabysmo) based on ethnic origin or gender.
Toxicology: Nonclinical Safety: Carcinogenicity: No studies have been performed to establish the carcinogenic potential of Faricimab (Vabysmo).
Genotoxicity: No studies have been performed to establish the mutagenic potential of Faricimab (Vabysmo).
Impairment of Fertility: No effects on reproductive organs were observed in a 6-month cynomolgus monkey study at faricimab doses up to 3 mg/eye (8-10x clinical exposures based on AUC).
Reproductive Toxicity: No effects on pregnancy or fetuses were observed in an embryo-fetal development study conducted in pregnant cynomolgus monkeys given 5 weekly intravenous injections of Faricimab (Vabysmo) at 1 mg/kg or 3 mg/kg, starting on day 20 of gestation. Serum exposure (C_max) in monkeys at the no observed adverse effect level (NOAEL) dose of 3 mg/kg was more than 500 times that in humans at a dose of 6 mg given by intravitreal injection once every 4 weeks.

Faricimab (Vabysmo) is indicated for the treatment of: Neovascular (wet) age-related macular degeneration (nAMD); Diabetic macular edema (DME); Macular edema secondary to retinal vein occlusion (branch retinal vein occlusion BRVO and central vein occlusion CRVO).

General: For intravitreal injection only. Faricimab (Vabysmo) 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): The recommended dose for Faricimab (Vabysmo) is 6 mg (0.05 mL) administered by intravitreal injection every 4 weeks (approximately every 28 ± 7 days, monthly) for the first 4 doses, followed by 6 mg (0.05 mL) via intravitreal injection at a dosing interval of up to every 16 weeks (4 months). The dosing interval should be based on the physician's judgment of the individual patient's retinal thickness (Central Subfield Thickness, CST) and/or visual acuity. Some patients may be dosed as frequently as every 4 weeks (approximately every 28 ± 7 days, monthly).
Monitoring between the dosing visits should be scheduled based on the patient's status and at the physician's discretion.
Diabetic macular edema (DME): The recommended dose for Faricimab (Vabysmo) is 6 mg (0.05 mL) administered by intravitreal injection every 4 weeks (approximately every 28 days ± 7 days, monthly) for the first 4 doses. Thereafter, treatment may be individualised using a treat-and-extend approach. Based on the physician's judgement of the individual patient's CST and/or visual acuity, the dosing interval may be extended up to a maximum of every 16 weeks (4 months), in increments of up to 4 weeks. The treatment interval is to be shortened accordingly in the event of deterioration in the CST and/or visual acuity (see Pharmacology: Pharmacodynamics: Mechanism of Action 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.
Macular edema secondary to retinal vein occlusion (BRVO and CRVO): The recommended dose for Faricimab (Vabysmo) is 6 mg (0.05 mL) administered by intravitreal injection every 4 weeks (approximately every 28 days ± 7 days, or once a month); three or more consecutive, monthly injections may be needed, until maximum visual acuity is achieved and/or no signs of disease activity are seen. Thereafter, treatment may be individualised using a treat-and-extend approach. Based on the physician's judgement of the individual patient's CST and/or visual acuity, the dosing interval may be extended. The treatment interval is to be shortened accordingly in the event of deterioration in the CST and/or visual acuity and any renewed extension to the treatment interval after stabilisation must be weighed up carefully (see Pharmacology: Pharmacodynamics: Mechanism of Action under Actions). Treatment intervals longer than 4 months between injections have not been studied.
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.
Mode of administration: Faricimab (Vabysmo) should be inspected visually for particulate matter and discoloration 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. Sterile equipment for paracentesis should be available in the event it 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.
Comprehensive instructions for the administration of Faricimab (Vabysmo) are given in the Instructions for Use under Patient Counselling Information.
Duration of treatment: Faricimab (Vabysmo) is intended for long-term treatment.
Delayed or missed dose: If an injection 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 (Vabysmo) should be discontinued.
Dose modifications following undesirable effects/interactions: No dose modifications of Faricimab (Vabysmo) are recommended.
Special Dosage Instructions: Pediatric use: The safety and efficacy of Faricimab (Vabysmo) in pediatric patients have not been established.
Geriatric use: In the six Phase III clinical studies, approximately 58% (1,496/2,571) of patients randomized to treatment with Faricimab (Vabysmo) were ≥65 years of age. Population pharmacokinetic analysis has shown an effect of age on ocular pharmacokinetics of faricimab. But the effect was considered not clinically meaningful. No significant differences in efficacy or safety of faricimab were determined with increasing age in these studies. No dose adjustment is required in patients ≥65 years of age (see Pharmacology: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions).
Renal impairment: No specific studies in patients with renal impairment have been conducted with Faricimab (Vabysmo) (see Pharmacology: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions).
However, no dose adjustment is required in patients with renal disorders.
Hepatic impairment: No specific studies in patients with hepatic impairment have been conducted with Faricimab (Vabysmo) (see Pharmacology: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions).
However, no dose adjustment is required in patients with hepatic impairment.
Other special patient populations: No special dosage modification is required for any of the populations that have been studied (e.g., elderly, gender, race).

Doses higher than the recommended dosing regimen have not been studied. Overdosing with greater than recommended injection volume may increase intraocular pressure.
In the event of an overdose, IOP should be monitored and, if deemed necessary by the treating physician, appropriate treatment should be initiated.

Faricimab (Vabysmo) is contraindicated in patients with ocular or periocular infections.
Faricimab (Vabysmo) is contraindicated in patients with active intraocular inflammation.
Faricimab (Vabysmo) is contraindicated in patients with known hypersensitivity to faricimab or any of the excipients. Hypersensitivity reactions may manifest as rash, pruritus, urticaria, erythema, or severe intraocular inflammation.

General: In order to improve traceability of biological medicinal products, the trade name and the batch number of the administered product should be clearly recorded.
Intravitreal injection-related reactions: Intravitreal injections, including those with Faricimab (Vabysmo) have been associated with endophthalmitis, intraocular inflammation, rhegmatogenous retinal detachment, retinal tear and iatrogenic traumatic cataract. Proper aseptic injection techniques must always be used when administering Faricimab (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.
Transient increases in intraocular pressure (IOP) have been seen within 60 minutes of intravitreal injection, including those with Faricimab (Vabysmo). Special precaution is needed in patients with poorly controlled glaucoma (do not inject Faricimab (Vabysmo) while the IOP is ≥30 mmHg). In all cases, both the IOP and perfusion of the optic nerve head and/or vision must be monitored and managed appropriately.
Systemic effects: Systemic adverse events, including arterial thromboembolic events, have been reported and there is a theoretical risk that these may be related to VEGF inhibition. A low incidence of arterial thromboembolic events was observed in the faricimab clinical trials in patients with nAMD, DME, BRVO and CRVO.
Immunogenicity: The active substance in Faricimab (Vabysmo) is a therapeutic protein. An immunological reaction to Faricimab (Vabysmo) is therefore possible. Patients should be instructed to report 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.
Bilateral Treatment: The safety and efficacy of Faricimab (Vabysmo) administered in both eyes have not been studied.
Concomitant use of other anti-VEGF medicinal products: There are no data available on the concomitant use of Faricimab (Vabysmo) with anti-VEGF medicinal products in the same eye.
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 Faricimab (Vabysmo) therapy, caution should be used in patients with these risk factors for retinal pigment epithelial tears.
Populations with limited data: There is only limited experience in the treatment of DME patients with HbA1c over 10%, patients with high-risk proliferative diabetic retinopathy (DR), or nAMD-, DME-, BRVO- and CRVO-patients with active systemic infections. There is also no experience of treatment with Faricimab (Vabysmo) of diabetic patients with uncontrolled hypertension. This lack of information should be considered by the physician when treating such patients.
Other Information: Faricimab (Vabysmo) solution for injection for intravitreal use contains less than 1 mmol sodium (23 mg) per dose, i.e. is essentially sodium-free.
Drug Abuse and Dependence: There is no evidence that Faricimab (Vabysmo) has the potential for drug abuse and dependence.
Renal Impairment: No dose adjustment is required in patients with renal impairment (see Special Dosage Instructions under Dosage & Administration and Pharmacology: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions).
Hepatic Impairment: The safety and efficacy of Faricimab (Vabysmo) in patients with hepatic impairment has not been studied (see Special Dosage Instructions under Dosage & Administration and Pharmacology: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions).
Ability to Drive and Use Machines: Faricimab (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.
Use in Children: The safety and efficacy of Faricimab (Vabysmo) in pediatric patients have not been established.
Use in the Elderly: In the six Phase III clinical studies, approximately 58% (1,496/2,571) of patients randomized to treatment with Faricimab (Vabysmo) were ≥65 years of age. No significant differences in efficacy or safety of Faricimab (Vabysmo) were seen with increasing age in these studies (see Special Dosage Instructions under Dosage & Administration and Pharmacology: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions).

Females and Males of Reproductive Potential: Fertility: No reproductive or fertility studies have been conducted. No effects on reproductive organs were observed in a 6-month cynomolgus monkey study at faricimab doses up to 3 mg/eye (8-10x clinical exposures based on AUC). 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-fetal development, however the risk is considered low due to the low systemic exposure after ocular administration.
Contraception: Women of childbearing potential should use effective contraception during treatment with Faricimab (Vabysmo) and for at least 3 months following the last dose of Faricimab (Vabysmo).
Pregnancy: There is no data from the use of Faricimab (Vabysmo) in pregnant women.
No adverse effects were observed in a study in pregnant cynomolgus monkeys (see Pharmacology: Toxicology: Nonclinical Safety: Reproductive toxicity under Actions).
VEGF inhibition has been shown to cause malformations, embryo-fetal resorption, and decreased fetal weight. VEGF inhibition has also been shown to affect follicular development, corpus luteum function, and fertility. No dedicated studies addressing the effects of Ang-2 inhibition on pregnancy are available. Based on non-clinical data, Ang-2 inhibition may lead to effects comparable to VEGF inhibition. Systemic exposure after ocular administration of Faricimab (Vabysmo) is very low.
It is not known whether faricimab can cross the placenta or cause harm to the fetus 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-fetal development. Although the systemic exposure after ocular administration is very low, faricimab should not be used during pregnancy unless that treatment is required due to the clinical condition of the woman.
Labor and delivery: The safe use of Faricimab (Vabysmo) during labor and delivery has not been established.
Lactation: It is not known whether Faricimab (Vabysmo) is excreted in human breast milk. No studies have been conducted to assess the impact of Faricimab (Vabysmo) 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 (Vabysmo) 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 (Vabysmo) and any potential adverse effects on the breastfed child from Faricimab (Vabysmo).

Clinical Trials: Summary of the safety profile from clinical studies: The following safety data were derived from actively controlled (aflibercept) phase III studies.
A total of 4,489 patients constituted the safety population in the six phase III clinical studies (2,567 patients treated with Faricimab (Vabysmo); 664 with nAMD, 1,262 with DME and 641 with BRVO and CRVO). The most serious adverse reactions were serious cataracts (0.8%), uveitis (0.5%), endophthalmitis (0.4%), vitritis (0.4%), retinal tears (0.2%), rhegmatogenous retinal detachment (0.1%) and traumatic cataract (<0.1%).
The most frequently reported adverse reactions in patients treated with Faricimab (Vabysmo) were cataracts (10%), conjunctival hemorrhage (7%), vitreous detachment (4%), IOP increased (4%), vitreous opacities (4%), eye pain (3%) and retinal pigment epithelial tear (nAMD only) (3%).
List of adverse reactions: The safety data described as follows include all adverse reactions from the six phase III clinical studies in the indications nAMD, DME, BRVO and CRVO, as well as from post-marketing surveillance, with a reasonable possibility of causality attribution to the injection procedure or medicinal product. 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) and not known (frequency cannot be estimated from the available data). (See Table 9.)

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Description of selected adverse drug reactions from clinical trials: 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 (Vabysmo) clinical trials in patients with nAMD, DME, BRVO and CRVO. Across indications no notable difference between the groups treated with Faricimab (Vabysmo) and the comparator were observed.
Postmarketing Experience: Rare cases of retinal vasculitis and/or retinal occlusive vasculitis have been reported in the postmarketing setting. Retinal vasculitis and retinal occlusive vasculitis have also been reported in patients treated with other IVT therapies.

No drug-drug interaction studies have been performed with Faricimab (Vabysmo).

Special Instructions for Use, Handling and Disposal: Preparation for Administration: Faricimab (Vabysmo) is a sterile, preservative-free, clear to opalescent, colorless to brownish-yellow solution.
Do not shake.
Faricimab (Vabysmo) should be inspected visually upon removal from the refrigerator and prior to administration. The vial must not be used if particulates, cloudiness, or discoloration are visible.
The contents of the vial and transfer filter needle are sterile and intended for single use only. Do not use if the packaging, vial and/or transfer filter needle are damaged or have expired.
Use an aseptic technique during preparation of the intravitreal injection.
Instructions for administration: See Dosage & Administration for dosing instructions.
For detailed instructions on administration, refer to the Instructions for Use under Patient Counselling Information.
Incompatibilities: In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Disposal of unused/expired medicines: The release of pharmaceuticals into the environment should be minimized. Medicines should not be disposed of via wastewater, and disposal through household waste should be avoided.
The following points should be strictly adhered to regarding the use and disposal of syringes and other medicinal sharps: Needles and syringes should never be reused.
Place all used needles and syringes into a sharps container (puncture-proof disposable container).
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Store in a refrigerator at 2-8°C. Do not shake. Do not freeze.
Keep the vial in the original carton to protect from light.
Prior to use, the unopened vial of Faricimab (Vabysmo) may be kept at room temperature, 20°C to 25°C (68°F to 77°F), for up to 24 hours.
Ensure that the injection is given immediately after preparation of the dose.

Instructions for Use: The following information is intended for healthcare professionals only.
Preparation for Administration: Before you start: Read all the instructions carefully before using Faricimab (Vabysmo).
The Faricimab (Vabysmo) kit includes a glass vial and transfer filter needle. The glass vial is for a single dose only. The filter needle is for single use only.
Faricimab (Vabysmo) should be stored refrigerated at temperatures between 2°C to 8°C (36°F to 46°F).
Do not freeze.
Do not shake.
Allow Faricimab (Vabysmo) to reach room temperature, 20°C to 25°C (68°F to 77°F) before proceeding with the administration. Keep the vial in the original carton to protect from light.
The Faricimab (Vabysmo) vial may be kept at room temperature for up to 24 hours.
The Faricimab (Vabysmo) vial should be inspected visually prior to administration. Faricimab (Vabysmo) is a clear to opalescent and colorless to brownish-yellow liquid solution.
Do not use if particulates, cloudiness, or discoloration are visible.
Do not use if the packaging, vial and/or transfer filter needle are expired, opened, or have been tampered with.
Use aseptic technique to carry out the preparation of the intravitreal injection.
Instructions for use of vial: 1. Gather the following supplies: One Faricimab (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), note that a 30-gauge injection needle is recommended to avoid increased injection forces that could be experienced with smaller diameter needles; Alcohol swab (not included).
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 your 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 your 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.
Injection Procedure: 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.

Other Eye Preparations

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

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