Clinical efficacy and safety of ranibizumab in the treatment of wet age-related macular degeneration

ABSTRACT

Introduction: Although several approaches have been studied for treating wet age-related macular degeneration (w-AMD), currently, the most effective strategy in the management of this visual disorder is represented by anti-VEGF drugs. Among them, ranibizumab (RBZ) is widely adopted in clinical practice for treating w-AMD.

Areas covered: VEGF (vascular endothelial growth factor) is a hypoxia-induced growth factor promoting neoangiogenesis, which has been correlated to the pathogenesis of w-AMD.

RBZ is a humanized, recombinant, monoclonal antibody fragment (Fab), which binds all the isoform of VEGF-A and, therefore, exerts an inhibitory activity on the growth of new pathological vessels leading to the reabsorption of VEGF-related macular edema. The pivotal trials ANCHOR and MARINA revealed its clinical efficacy and good safety profile for treating w-AMD, leading ultimately to its FDA approval. Further trials have analyzed the best dosage and regimen modality, reporting RBZ at 0.5 mg with a ‘pro re nata’ regimen (PRN) to be non-inferior to the 0.5 mg formulation administered monthly. The treat-to-extend (TAE) regimen has also been investigated, demonstrating encouraging results in terms of clinical efficacy and nonetheless, it was proven to be a well-tolerated option with the possibility of reducing the treatment burden for the patients.

Conclusions: RBZ has been proven to be an effective anti-VEGF agent for treating w-AMD; however, more optimal therapeutic regimens and drug delivery systems are being investigated in order to improve patients’ compliance and treatment burden.

KEYWORDS:

• Ranibizumab
• macular degeneration
• retina
• OCT
• angiogenesis
• targeted therapy

Article Highlights

• RBZ is a human, monoclonal fragment (Fab) binding all the isoforms of VEGF-A and, thanks to its small molecular size (48 kDa), it can easily penetrate all the retinal and choroidal layers.

• The pivotal ANCHOR and MARINA trials led to RBZ approval for treating w-AMD. These trials showed its clinical efficacy in treating both classic and occult choroidal neovascularizations (CNV) in comparison with usual care (photodynamic therapy).

• Extrapolated data from HARBOR, PIER, SUSTAIN and EXCITE Trials revealed that the monthly regimen is more effective in gaining visual acuity (VA) in comparison with quaternary or as-needed regimens.

• The Treat and Extend (TAE) regimen has shown comparable results with monthly injections in the TAE and TREND Trials. Moreover, this protocol would allow to reduce the treatment burden for the patient and is being largely employed in the clinical practice.

• Ongoing phase II/III Trials are investigating new deliveries modalities, like RBZ Port Delivery System (RPDS), in the management of w-AMD.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.