Introduction
Byooviz™ (ranibizumab-nuna) is a biosimilar to Lucentis® (ranibizumab) that was approved by the FDA in September 2021. It is a vascular endothelial growth factor (VEGF) inhibitor indicated for the treatment of various retinal vascular conditions. Byooviz represents the first biosimilar approved for ophthalmologic use in the United States, offering a potentially more accessible treatment option for vision-threatening conditions.
Mechanism of Action
Ranibizumab-nuna is a recombinant humanized IgG1 kappa isotype monoclonal antibody fragment that binds to and inhibits biologically active forms of human vascular endothelial growth factor A (VEGF-A). By inhibiting VEGF-A, Byooviz prevents its binding to VEGF receptors (VEGFR-1 and VEGFR-2) on the surface of endothelial cells. This inhibition reduces endothelial cell proliferation, vascular leakage, and new blood vessel formation, thereby slowing the progression of neovascular retinal diseases.
Indications
Byooviz is FDA-approved for:
- Neovascular (wet) age-related macular degeneration (AMD)
- Macular edema following retinal vein occlusion (RVO)
- Diabetic macular edema (DME)
- Diabetic retinopathy (DR) in patients with DME
- Myopic choroidal neovascularization (mCNV)
Dosage and Administration
Recommended dosage: 0.5 mg (0.05 mL) administered by intravitreal injection once monthly Administration:- For wet AMD: 0.5 mg monthly
- For RVO, DME, and DR with DME: Initial monthly injections; may individualize based on treatment response
- For mCNV: Up to 3 monthly injections; may individualize thereafter
- Must be administered by a qualified physician using aseptic technique
- Prior to injection, administer topical anesthetic and broad-spectrum microbicide
- No dosage adjustment recommended for renal or hepatic impairment
- Safety and effectiveness in pediatric patients not established
Pharmacokinetics
Absorption: Administered via intravitreal injection with systemic absorption expected to be low Distribution: VEGF inhibition primarily occurs in the eye; systemic exposure is minimal Metabolism: Expected to undergo proteolytic degradation like other antibody fragments Elimination: Systemic elimination follows linear pharmacokinetics with an estimated half-life of approximately 9 days in serum Ocular pharmacokinetics: Mean vitreous elimination half-life of approximately 9 days in humansContraindications
- Ocular or periocular infections
- Active intraocular inflammation
- Hypersensitivity to ranibizumab-nuna or any component of the formulation
- Known hypersensitivity to other VEGF inhibitors
Warnings and Precautions
Boxed Warning: Endophthalmitis and retinal detachments may occur following intravitreal injections Additional warnings:- Increases in intraocular pressure within 60 minutes of injection
- Thromboembolic events (myocardial infarction, cerebrovascular accidents)
- Potential for arterial thromboembolic events
- Non-infectious intraocular inflammation
- Retinal pigment epithelial tears (primarily in AMD patients)
- Potential for immunogenicity
- Patients may experience temporary visual disturbances after injection
Drug Interactions
- Limited formal interaction studies conducted
- Theoretical potential for interactions with other VEGF inhibitors when administered systemically
- No clinically significant pharmacokinetic interactions expected with concomitant ocular medications
- Caution advised when using with other antiangiogenic agents due to potential additive effects
Adverse Effects
Most common adverse reactions (≥5%):- Conjunctival hemorrhage (25-80%)
- Eye pain (10-40%)
- Vitreous floaters (10-30%)
- Intraocular pressure increased (15-25%)
- Vitreous detachment (10-20%)
- Cataract (5-15%)
- Endophthalmitis (≤1%)
- Retinal detachment (≤1%)
- Rhegmatogenous retinal detachment
- Intraocular inflammation
- Arterial thromboembolic events (≤1%)
- Ocular hypersensitivity reactions
Monitoring Parameters
Prior to each injection:- Visual acuity assessment
- Intraocular pressure measurement
- Ophthalmoscopic examination
- Assessment for signs of ocular infection or inflammation
- Regular monitoring for changes in visual acuity
- Assessment for signs of intraocular inflammation/infection
- Monitoring for increased intraocular pressure
- Evaluation for arterial thromboembolic events in at-risk patients
- Regular retinal examinations
- Assessment for cataract development
- Monitoring for systemic adverse events in patients with cardiovascular risk factors
Patient Education
- Report any eye pain, redness, sensitivity to light, or vision changes immediately
- Understand that temporary visual disturbances may occur after injection
- Be aware of potential signs of infection (increasing eye redness, pain, vision changes)
- Understand the importance of regular follow-up appointments
- Inform all healthcare providers of Byooviz treatment
- Report any chest pain, limb weakness, or speech difficulties promptly
- Do not drive or operate machinery until vision has stabilized after injection
- Understand that multiple injections are typically required for optimal efficacy
References
1. FDA Approval Letter: Byooviz (ranibizumab-nuna). September 2021 2. Byooviz [package insert]. Cambridge, MA: Biogen Inc.; 2021 3. Heier JS, et al. Ranibizumab for treatment of neovascular age-related macular degeneration. Ophthalmology. 2012;119(12):2537-2548 4. Brown DM, et al. Ranibizumab for macular edema following central retinal vein occlusion. Ophthalmology. 2010;117(6):1124-1133 5. Nguyen QD, et al. Ranibizumab for diabetic macular edema. Ophthalmology. 2012;119(4):789-801 6. Schmidt-Erfurth U, et al. Efficacy and safety of monthly versus quarterly ranibizumab treatment in neovascular age-related macular degeneration. Ophthalmology. 2011;118(5):831-839 7. Rosenfeld PJ, et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006;355(14):1419-1431
This information is intended for educational purposes only and does not replace professional medical advice. Always consult with a qualified healthcare provider for personalized medical guidance.