Lucentis

Ranibizumab injection

GENENTECH

Monoclonal antibody approved for age-related macular degeneration

Efficacy. The efficacy of ranibizumab in the treatment of neovascular AMD was evaluated in 3 randomized, double-blinded, sham- or active-controlled studies in 1,323 patients. In Study 1, patients with minimally classic or occult (without classic) choroidal neovascularization (CNV) lesions received monthly ranibizumab 0.3- or 0.5-mg intravitreal injections or monthly sham injections. In Study 2, patients with predominantly classic CNV lesions received 1 of the following: 1) monthly ranibizumab 0.3-mg intravitreal injections and sham photodynamic therapy (PDT); 2) monthly ranibizumab 0.5-mg intravitreal injections and sham PDT; 3) sham intravitreal injections and active verteporfin PDT. In both studies, the primary efficacy end point was the proportion of patients who maintained vision, defined as losing fewer than 15 letters of visual acuity at 12 months compared with baseline. Nearly all ranibizumab-treated patients (approximately 95%) maintained their visual acuity, and 34% to 40% of ranibizumab- treated patients experienced a clinically significant improvement in vision, defined as gaining 15 or more letters at 12 months. The mean change in visual acuity (letters) for the ranibizumab 0.5-mg arm in Study 1 was +7.2 at 12 months versus –10.5 for the sham arm (P<.01). In Study 2, the mean change in visual acuity at 12 months was +11.3 for patients receiving 0.5-mg ranibizumab injections compared with –9.5 for patients receiving sham therapy (P<.01). Study 3 was a randomized, double-blinded, sham-controlled, 2-year study designed to assess the safety and efficacy of ranibizumab in patients with neovascular AMD (with or without a classic CNV component). Patients enrolled in the trial received ranibizumab 0.3- or 0.5-mg intravitreal injections or sham injections once every 3 months, with the efficacy end point being the change in visual acuity at 12 months compared with baseline. On average, patients dosed with ranibizumab lost visual acuity, returning to baseline at Month 12, with 90% maintaining visual acuity from that point.

Safety. Ranibizumab is contraindicated in patients with ocular or periocular infections. Intravitreal injections, including those with ranibizumab, have been associated with endophthalmitis and retinal detachments. Proper aseptic injection technique should always be used when administering ranibizumab, and patients should be monitored during the week following the injection to permit early treatment should an infection occur. Increases in intraocular pressure have been reported within 60 minutes of intravitreal injection with ranibizumab. Accordingly, intraocular pressure as well as the perfusion of the optic nerve head should be monitored and managed appropriately. A theoretical risk of arterial thromboembolic events exists following intravitreal use of VEGF inhibitors such as ranibizumab. The most commonly reported adverse events associated with ranibizumab intravitreal injection include conjunctival hemorrhage, eye pain, vitreous floaters, increased intraocular pressure, and intraocular inflammation.

Dosing. Ranibizumab 0.5 mg should be administered via an intravitreous injection once a month. Although less effective, treatment may be reduced to 1 injection every 3 months after the first 4 injections if monthly injections are not feasible. Compared with continued monthly dosing, dosing every 3 months will result in an approximate 5-letter (1-line) loss of visual acuity benefit, on average, over the following 9 months. Patients should be evaluated regularly when employing this dosing schedule.