Vabysmo

VABYSMO for injection 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.
Excipients/Inactive Ingredients: L-Histidine, Acetic Acid 30%, L-Methionine, Sodium Chloride, D-Sucrose, Polysorbate 20 and 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.
Pharmacodynamic effects: A decrease from baseline of ocular free Ang-2 and free VEGF-A concentrations was observed from day 7 onwards throughout the treatment interval (in most patients) in the four Phase III clinical studies.
In Phase III studies in patients with nAMD (TENAYA, 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 week 48 with VABYSMO, and were comparable to those observed with aflibercept. The mean CST reduction from baseline to 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.
There was a comparable effect of VABYSMO and aflibercept on the reduction of intraretinal fluid (IRF), subretinal fluid (SRF), and pigment epithelial detachment (PED). At the primary endpoint visits (min-max, weeks 40-48), the proportion of patients in TENAYA and LUCERNE, respectively, with absence of IRF was: 76%-82% and 78%-85% in VABYSMO vs. 74%-85% and 78%-84% in aflibercept; absence of SRF: 70%-79% and 66%-78% in VABYSMO vs. 66%-78% and 62%-76% in aflibercept; absence of PED: 3%-8% and 3%-6% in VABYSMO vs. 8%-10% and 7%-9% in aflibercept.
At week 48, there was comparable change in total CNV lesion area from baseline across treatment arms (0.0 mm2 and 0.4 mm2 in VABYSMO vs. 0.4 mm2 and 1.0 mm2 in aflibercept, in TENAYA and LUCERNE, respectively). There was a comparable reduction in CNV leakage area from baseline across treatment arms (-3.8 mm2 and -3.2 mm2 in VABYSMO and -3.0 mm2 and -2.2 mm2 in aflibercept, in TENAYA and LUCERNE, respectively).
In Phase III studies in patients with DME (YOSEMITE and RHINE), anatomic parameters related to macular edema were part of the disease activity assessments guiding treatment decisions.
The reductions in mean CST from baseline were numerically greater in patients treated with VABYSMO every 8 weeks (Q8W) and VABYSMO up to Q16W adjustable dosing as compared to aflibercept Q8W from week 4 to week 100 in both YOSEMITE and RHINE. Greater proportions of patients in both VABYSMO arms achieved absence of IRF and absence of DME (defined as reaching CST below 325 µm) as measured on Spectral Domain Optical Coherence Tomography (SD-OCT) over time in both studies, compared to the aflibercept arm. Comparable reductions in SRF were observed across both 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 48-56) was 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. These mean CST reductions were maintained through year 2. The proportion of patients with absence of DME at primary endpoint visits (min-max, weeks 48-56) were 77%-87% and 80%-82% in patients treated with VABYSMO Q8W and VABYSMO up to Q16W adjustable dosing, as compared to 64%-71% in aflibercept Q8W patients in YOSEMITE; results were 85%-90%, 83%-87%, and 71%-77%, respectively in RHINE. These results were maintained through year 2.
At week 16, the proportion of patients with absence of IRF was numerically greater in patients receiving VABYSMO Q8W or VABYSMO up to Q16W adjustable dosing versus aflibercept Q8W dosing in both studies (YOSEMITE: 16% and 22% vs. 13%; RHINE: 20% and 20% vs. 13%). The proportions of patients with absence of IRF at primary endpoint visits (min-max, weeks 48-56) were 42%-48% and 34%-43% in patients treated with VABYSMO Q8W and VABYSMO up to Q16W adjustable dosing, as compared to 22%-25% in aflibercept Q8W patients in YOSEMITE; results were 39%-43%, 33%-41%, and 23%-29%, respectively in RHINE.
Clinical efficacy and safety: Treatment of nAMD: The safety and efficacy of VABYSMO (faricimab) were assessed in two randomized, multi-center, double-masked, active comparator-controlled studies in patients with nAMD, TENAYA (NCT03823287) and LUCERNE (NCT03823300). A total of 1,329 patients were enrolled in these studies, and 1,326 patients received at least one dose (664 with VABYSMO). Patient ages ranged from 50 to 99 with a mean of 75.9 years.
In both studies, patients were randomized 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 randomized 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 visual and anatomic criteria as well as treating physician clinical assessment. Patients remained on these fixed dosing intervals until week 60 without supplemental therapy.
The primary efficacy endpoint was the change from baseline in BCVA based on an average at weeks 40, 44, and 48, measured by the Early Treatment Diabetic Retinopathy Study (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.
The proportion of patients on each of the different treatment intervals at week 48 in TENAYA and LUCERNE, respectively was: Q16W: 46%, 45%; Q12W: 34%, 33%; Q8W: 20%, 22%. (See Table 1 and Figures 1 & 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.
Treatment of DME: The safety and efficacy of VABYSMO were assessed in two randomized, multi-centre, double-masked, active comparator-controlled 2-year studies (YOSEMITE and RHINE) in patients with DME. A total of 1,891 patients were enrolled in the two studies with 1,622 (86%) patients completing the studies through week 100. A total of 1,887 patients 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 naive patients (78%) and patients who had been previously treated with a VEGF inhibitor prior to study participation (22%). In both studies, patients were randomized 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 Q16W adjustable dosing arm, the dosing interval could be increased in 4-week increments or could be decreased in 4- or 8-week increments based on automated objective assessment of pre-specified visual and anatomic disease activity criteria.
Both studies demonstrated efficacy in the primary endpoint, defined as the 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.
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 & 4.)

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Efficacy results in patients who were anti-VEGF treatment naive 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.
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 National Eye Institute Visual Function Questionnaire (NEI VFQ-25) composite score that was 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 pre-specified 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.
An additional key efficacy outcome in DME 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 non-proliferative 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. The proportion of patients with a ≥ 2-step improvement on the ETDRS-DRSS at baseline, week 16, week 52 and at week 96 are shown in Figures 5 and 6 as follows. (See Table 3 and Figure 5 & 6.)

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The proportions of patients with new proliferative DR diagnosis (defined by ETDRS-DRSS 61 or worse) from baseline to week 96 were comparable between the VABYSMO Q8W, VABYSMO up to Q16W adjustable dosing and aflibercept Q8W dosed patients in both YOSEMITE and RHINE studies.
Almost no patients required vitrectomy (0 to 4 per group) or Panretinal Photocoagulation (PRP) (1 to 2 per group) during the two year duration of the studies.
DR treatment effects in the subgroup of patients who were anti-VEGF naive 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.
Treatment effects in subgroups by DR severity at baseline were different and showed the greatest ≥ 2-step DRSS improvements among patients with moderately severe and severe non-proliferative DR with approximately 90% of patients achieving improvements. These results were comparable across the study arms, and comparable in overall and anti-VEGF treatment-naive populations.
Immunogenicity: Immunogenicity assay results are highly dependent on several factors including assay sensitivity and specificity, assay methodology, sample handling, timing of sample collection, concomitant medications and underlying disease. For these reasons, comparison of incidence of antibodies to VABYSMO with the incidence of antibodies to other products may be misleading.
In the nAMD and DME studies, the pre-treatment incidence of anti-faricimab antibodies was approximately 1.8% and 0.8%, respectively. After initiation of dosing, anti-faricimab antibodies were detected in approximately 10.4% and 8.4% of patients with nAMD and DME respectively, treated with VABYSMO across studies and across treatment groups. As with all therapeutic proteins, there is the potential for immune response to VABYSMO.
Pharmacokinetics: Absorption: 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 (Cmax) are estimated to occur approximately 2 days post-dose. Mean (± SD) plasma Cmax are estimated 0.23 (0.07) µg/mL and 0.22 (0.07) µg/mL respectively in nAMD and in DME/DR 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.
Distribution: Maximum plasma free faricimab concentrations are predicted to be approximately 600 and 6000-fold lower than in aqueous and vitreous humor respectively and are below the binding affinity for VEGF and Ang-2. Therefore, systemic pharmacodynamic 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.
Metabolism: The metabolism of faricimab has not been directly studied, as monoclonal antibodies are cleared principally by catabolism.
Elimination: The estimated mean apparent systemic half-life of faricimab is 7.5 days after IVT administration.
Pharmacokinetics in special populations: Pediatric Population: The safety and efficacy of VABYSMO in pediatric patients have not been established.
Geriatric Population: In the four Phase III clinical studies, approximately 60% (1,149/1,929) of patients randomized to treatment with VABYSMO were ≥ 65 years of age. Population pharmacokinetic analysis has shown an effect of age on ocular pharmacokinetics of faricimab. The effect was considered not clinically meaningful.
Renal impairment: No formal pharmacokinetic study has been conducted in patients with renal impairment.
Hepatic impairment: No formal pharmacokinetic study has been conducted in patients with hepatic impairment.
Other: The systemic pharmacokinetics of VABYSMO are not influenced by race. Gender was not shown to have a clinically meaningful influence on systemic pharmacokinetics of VABYSMO.
Toxicology: Preclinical safety data: Impairment of fertility: While the anti-VEGF and anti-Ang2 components could mean a potential theoretical mechanism-based risk to reproduction, the systemic exposure stemming from intravitreal treatment suggests that this risk may be negligible. No effects on fertility were observed in a 6-month cynomolgus monkey study with VABYSMO.
Genotoxicity: No studies have been performed to establish the mutagenic potential of VABYSMO.
Reproductive toxicity: 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 information Ang-2 inhibition may lead to effects comparable to VEGF inhibition. Systemic exposure after ocular administration of VABYSMO is very low.
No effects on reproductive organs were observed in a 6-month cynomolgus monkey study with VABYSMO. No effects on pregnancy or fetuses were observed in an embryo-fetal development study in pregnant cynomolgus monkeys given 5 weekly IV injections of VABYSMO starting on day 20 of gestation at 1 mg/kg or 3 mg/kg. Serum exposure (Cmax) 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.
Carcinogenicity: No carcinogenicity studies have been performed to establish the carcinogenic potential of VABYSMO.

VABYSMO is a bispecific angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF) inhibitor indicated for the treatment of: Neovascular (wet) age-related macular degeneration (nAMD); Diabetic macular edema (DME).

General: For intravitreal injection only. 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 VABYSMO is 6 mg (0.05 mL) administered by intravitreal injection every 4 weeks (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). 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 VABYSMO is 6 mg (0.05 mL) administered by intravitreal injection every 4 weeks (monthly) for the first 4 doses, followed by 6 mg (0.05 mL) via intravitreal injection at intervals of up to every 16 weeks (4 months). Monitoring between the dosing visits should be scheduled based on the patient's status and at the physician's discretion.
Method of administration: 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. 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.
Comprehensive instructions for the administration of VABYSMO are given in the Instructions for Use.
Duration of treatment: VABYSMO is intended for long-term treatment.
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, VABYSMO should be discontinued.
Dose Modifications: No dose modifications of VABYSMO are recommended.
Special Dosage Instructions: Pediatric use: The safety and efficacy of VABYSMO in pediatric patients have not been established.
Geriatric use: In the four Phase III clinical studies, approximately 60% (1,149/1,929) of patients randomized to treatment with VABYSMO were ≥ 65 years of age. Population pharmacokinetic analysis has shown an effect of age on ocular pharmacokinetics of faricimab. The effect was considered not clinically meaningful. No dose adjustment is required in patients ≥ 65 years of age (see Use in the Elderly under Precautions and Pharmacology: Pharmacokinetics: Pharmacokinetics in special populations under Actions).
Renal Impairment: No specific studies in patients with renal impairment have been conducted with VABYSMO. Pharmacokinetic analysis of patients in all 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 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.

VABYSMO is contraindicated in patients with ocular or periocular infections.
VABYSMO is contraindicated in patients with active intraocular inflammation.
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 VABYSMO have been associated with endophthalmitis, intraocular inflammation, rhegmatogenous retinal detachment and retinal tear. 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.
Transient increases in intraocular pressure (IOP) have been seen within 60 minutes of intravitreal injection, including those with VABYSMO. 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 and/or vision must be monitored and managed appropriately.
Systemic effects: Systemic adverse events including arterial thromboembolic events have been reported following intravitreal injection of VEGF inhibitors and there is a theoretical risk that these may be related to VEGF inhibition.
Immunogenicity: As with all therapeutic proteins, there is the potential for immune response to VABYSMO. 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 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 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 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 and DME 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.
Drug Abuse and Dependence: There is no evidence that 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 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).
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.
Use in Children: The safety and efficacy of VABYSMO in pediatric patients have not been established.
Use in the Elderly: In the four Phase III clinical studies, approximately 60% (1,149/1,929) of patients randomized to treatment with VABYSMO were ≥ 65 years of age. No significant differences in efficacy or safety of 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).

Fertility: 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 VABYSMO. 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 (see Pharmacology: Toxicology: Preclinical safety data: Impairment of fertility under Actions).
Contraception: Women of childbearing potential should use contraception during treatment with VABYSMO and for at least 3 months following the last dose of VABYSMO.
Pregnancy: There are no data from the use of VABYSMO in pregnant women.
No adverse effects were observed in a study in pregnant cynomologus monkeys given VABYSMO intravenously throughout the period of organogenesis at doses achieving more than 500 times the predicted systemic human exposure of VABYSMO after treatment of a single eye (see Pharmacology: Toxicology: Preclinical safety data: Reproductive toxicity under Actions).
It is not known whether VABYSMO 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, VABYSMO should not be used during pregnancy unless the potential benefit to the patient outweighs the potential risk to the fetus.
Labor and Delivery: The safe use of VABYSMO during labor and delivery has not been established.
Lactation: It is not known whether VABYSMO is excreted in human breast milk. No studies have been conducted to assess the impact of 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 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 VABYSMO and any potential adverse effects on the breastfed child from VABYSMO.

Clinical Trials: Summary of the safety profile: A total of 3,213 patients constituted the safety population in the four Phase III clinical studies (1,926 VABYSMO treated patients; 664 in nAMD and 1,262 in DME).
The most serious adverse reactions were uveitis (0.5%), endophthalmitis (0.3%), vitritis (0.3%), retinal tear (0.2%), and rhegmatogenous retinal detachment (< 0.1%).
The most frequently reported adverse reactions in patients treated with VABYSMO were cataract (11%), conjunctival hemorrhage (7%), IOP increased (4%), vitreous floaters (4%), eye pain (3%) and retinal pigment epithelial tear (nAMD only) (3%).
Tabulated summary of adverse drug reactions from clinical trials: The safety data described as follows include all adverse reactions from the pooled data across four Phase III clinical studies in the indications nAMD and DME, 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). (See Table 4.)

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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 VABYSMO clinical trials in patients with nAMD and DME. Across indications no notable difference between the groups treated with VABYSMO and the comparator were observed.
Postmarketing Experience: Not applicable.

No drug-drug interaction studies have been performed with VABYSMO.

Incompatibilities: In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Special precautions for disposal and other handling: Preparation for Administration: VABYSMO is a sterile, preservative-free, clear to opalescent, colorless to brownish-yellow solution.
Do not shake.
VABYSMO should be inspected visually upon removal from the refrigerator and prior to administration. If particulates, cloudiness, or discoloration are visible, the vial must not be used.
The contents of the vial and 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.
Use aseptic technique for preparation of the intravitreal injection.
Instructions for administration: See Dosage & Administration.
For detailed instructions on administration, refer to the Instructions for Use.
Packs: 1 vial containing solution for injection co-packaged with a transfer filter needle.
Disposal of unused/expired medicines: The release of pharmaceuticals in 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 at 2°C - 8°C protected from light.
Do not freeze.
Keep the vial in the original carton to protect from light.
Prior to use, the unopened vial of 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.

Other Eye Preparations

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

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