Vabysmo

Approved Indications:

• Neovascular (Wet) Age-related Macular Degeneration (nAMD):
• Treatment of choroidal neovascularization secondary to age-related macular degeneration.
• Applicable to both treatment-naïve and previously treated patients.
• Diabetic Macular Edema (DME):
• Treatment of macular edema due to diabetic retinopathy.
• Approved for patients with visual impairment due to DME.

Clinically Accepted Off-Label Uses:

• Macular Edema Secondary to Retinal Vein Occlusion (RVO): Being explored in trials; not officially approved, but considered for future indication.
• Polypoidal Choroidal Vasculopathy (PCV): Investigational use in some regions, with ongoing clinical study support.

Route: Intravitreal injection only
Strength: 120 mg/mL solution in 0.05 mL dose (6 mg)
Form: Single-use vial or prefilled syringe

For nAMD (Neovascular Age-related Macular Degeneration):

• Initial dosing: 6 mg intravitreal injection every 4 weeks (monthly) for 4 doses.
• Maintenance phase:
  • Based on disease activity, may extend to every 8, 12, or 16 weeks.
  • Clinical response assessed by retinal fluid status and vision.

For DME (Diabetic Macular Edema):

• Initial dosing: 6 mg intravitreal injection every 4 weeks for 4 doses.
• Maintenance phase:
  • Extend to every 8, 12, or 16 weeks depending on stability of disease.

Special Populations:

• Pediatrics: Not established; safety and efficacy not approved in patients under 18 years.
• Elderly: No specific dose adjustment required; monitor for adverse ocular effects.
• Hepatic Impairment: No dose adjustment required; systemic exposure is minimal.
• Renal Impairment: No adjustment needed; not systemically cleared.

Administration Notes:

• Administer under aseptic conditions.
• Avoid multiple injections on the same day in the same eye.
• Monitor intraocular pressure (IOP) and conduct perfusion check immediately post-injection.

Faricimab is a bispecific monoclonal antibody that uniquely targets both Angiopoietin-2 (Ang-2) and Vascular Endothelial Growth Factor-A (VEGF-A). By inhibiting VEGF-A, Faricimab prevents abnormal blood vessel growth and vascular permeability. Concurrently, Ang-2 blockade stabilizes blood vessels and prevents inflammation-induced vascular destabilization. The dual inhibition helps restore and maintain retinal vascular integrity, reduces macular edema, and improves visual outcomes in conditions such as nAMD and DME. This dual-target mechanism offers longer durability and more extended dosing intervals compared to anti-VEGF monotherapies.

• Absorption: Minimal systemic absorption post-intravitreal injection; detectable in low concentrations in plasma.
• Distribution: Localized distribution in ocular tissues; limited systemic exposure.
• Metabolism: Catabolized into small peptides and amino acids via standard proteolytic pathways.
• Elimination: Slow elimination from the vitreous; systemic elimination via the reticuloendothelial system.
• Half-life:
  • In vitreous: Approx. 9–12 days
  • In plasma: ~7 days
• Bioavailability: Local bioavailability is high post-intravitreal administration.
• Steady-State: Achieved after repeated monthly dosing.

Pregnancy:

• FDA Pregnancy Classification: Not assigned (modern labeling avoids letter categories).
• Summary: No adequate data in pregnant women. Animal studies indicate minimal systemic exposure. Use only if potential benefit justifies potential fetal risk.
• Recommendation: Avoid use during pregnancy unless clearly necessary.

Lactation:

• Unknown whether Faricimab is excreted in human milk.
• Systemic exposure is low; unlikely to affect breastfed infant.
• Decision should consider risk to infant and benefit to mother.
• Use caution during lactation due to lack of conclusive safety data.

• Primary Class: Dual pathway antiangiogenic agent
• Subclass: Bispecific monoclonal antibody targeting Ang-2 and VEGF-A
• Therapeutic Category: Intravitreal biologic for retinal vascular diseases
• Generation: First-in-class dual-action antibody for ophthalmologic use

• Known hypersensitivity to Faricimab or any of its excipients
• Active ocular or periocular infections (e.g., conjunctivitis, keratitis, endophthalmitis)
• Active intraocular inflammation (e.g., uveitis)
• Recent intraocular surgery with incomplete healing

• Endophthalmitis and Retinal Detachment: Risk following intravitreal injection. Use sterile injection technique and monitor patients closely.
• Intraocular Pressure Elevation: Transient increase may occur post-injection; monitor IOP.
• Arterial Thromboembolic Events: Potential systemic VEGF inhibition risk; low incidence but monitor high-risk patients.
• Inflammation: Cases of intraocular inflammation (IOI), including retinal vasculitis and occlusive vasculitis, have been reported; prompt evaluation recommended if inflammation is suspected.
• Bilateral Use: Not approved for bilateral simultaneous use.
• Pediatric Use: Not established; avoid in patients under 18 years.

Common Adverse Effects (≥1%):

• Ocular:
• Conjunctival hemorrhage
• Vitreous floaters
• Eye pain
• Intraocular pressure increase
• Blurred vision

Less Common:

• Eye irritation
• Foreign body sensation
• Dry eye
• Photophobia

Serious Adverse Effects (rare):

• Endophthalmitis
• Retinal detachment
• Retinal vasculitis
• Arterial occlusive events
• Intraocular inflammation

Timing & Dose-Dependence:

• Serious ocular events typically occur within days to weeks post-injection.
• Risk increases with improper administration or pre-existing inflammation.

• Systemic Drug Interactions: Unlikely due to negligible systemic exposure.
• Enzyme Pathways: Not metabolized by CYP450 enzymes.
• Drug-Food/Alcohol Interactions: None reported.
• Concomitant Intravitreal Therapies: Not recommended with other anti-VEGF agents or corticosteroids unless specifically indicated.

Precaution: Avoid use with other ocular immunosuppressive or anti-angiogenic therapies unless clinically justified.

• 2022 – FDA & EMA Approval: Faricimab approved as Vabysmo® for both nAMD and DME, marking the first dual-action antibody in ophthalmology.
• 2023 – Real-World Data: Supported extended dosing intervals (up to 16 weeks) in stable patients.
• 2024 – NICE (UK) Guidance: Recommended as a cost-effective alternative to aflibercept for nAMD and DME under extended interval protocols.
• 2025 – Ongoing Trials: Evaluating potential use in retinal vein occlusion (RVO) and other retinal disorders.

• Temperature Range: Store at 2°C to 8°C (36°F to 46°F)
• Do Not Freeze
• Light Protection: Store in original carton to protect from light
• Handling:
  • Do not shake
  • Inspect visually before use; do not use if discolored or contains particulate matter
  • Use immediately after opening vial/syringe
  • Discard any unused portion