Ranibizumab

Ranibizumab (trade name Lucentis) is a monoclonal antibody fragment derived from the same parent murine antibody as bevacizumab (Avastin). It is much smaller than the parent molecule and has been affinity matured to provide stronger binding to VEGF-A. It is an anti-angiogenic that has been approved to treat the "wet" type of age-related macular degeneration (ARMD), a common form of age-related vision loss.

Ranibizumab was developed by Genentech and is marketed in the United States by Genentech and elsewhere by Novartis, under the brand name Lucentis.

Mechanism of action
Ranibizumab binds to and inhibits all subtypes of vascular endothelial growth factor A (VEGF-A). VEGF may trigger the growth of new vessels, which may leak blood and fluid into the eye. These leaky blood vessels may contribute to macular edema and choroidal neovascularization, resulting in the wet type of ARMD.

By blocking VEGF-A in the eye, ranibizumab may prevent and reverse vision loss caused by wet macular degeneration.

Administration
The drug is injected intravitreally (into the vitreous humour of the eye) once a month. If monthly injections are not feasible, the regimen may be reduced to 1 injection every 3 months after the first 4 months.

However, dosing every 3 months is linked to a loss of approximately 5 letters (1 line) in visual acuity for the following 9 months as compared with dosing on a monthly basis. Large phase 3 clinical trials (MARINA and ANCHOR) which randomized patients with wet macular degeneration showed that 95% of ranibizumab-treated patients maintained visual acuity compared with 62% of those administered placebo (P < .01) at 1 year; moreover, up to 40% demonstrated an improvement in vision of at least 3 lines. Vision maintenance and loss were defined as a loss of less than 15 letters and a gain of 15 or more letters in visual acuity, respectively, as measured using the Early Treatment of Diabetic Retinopathy eye chart.

Side effects
The most common side effects in clinical trials were conjunctival hemorrhage, eye pain, vitreous floaters, increased intraocular pressure, and intraocular inflammation.

Although there is a theoretical risk for arterial thromboembolic events in patients receiving VEGF-inhibitors by intravitreal injection, the observed incidence rate was low (< 4%) and similar to that seen in patients randomized to placebo.

Serious adverse events related to the injection procedure occurred with an incidence rate of less than 1% and included endophthalmitis, retinal detachment, and traumatic cataracts. Other serious ocular adverse events observed among ranibizumab-treated patients (incidence rate, < 2%) included intraocular inflammation and increased intraocular pressure.