Ranibizumab safe, effective over long term in HORIZON extension study

May 6, 2009

Multiple intravitreal ranibizumab (Lucentis, Genentech) was safe and effective over the long term for treating subfoveal choroidal neovascularization (CNV) in age-related degeneration (AMD) in the 2-year open-label, multicenter HORIZON extension study, said Michael Singer, MD, Medical Center Ophthalmology Associates, San Antonio, TX.

Fort Lauderdale, FL-Multiple intravitreal ranibizumab (Lucentis, Genentech) was safe and effective over the long term for treating subfoveal choroidal neovascularization (CNV) in age-related degeneration (AMD) in the 2-year open-label, multicenter HORIZON extension study, said Michael Singer, MD, Medical Center Ophthalmology Associates, San Antonio, TX.

The HORIZON study included 853 patients (600 previously had been treated with ranibizumab initially, 184 had crossed over to treatment with ranibizumab, and 69 had not been treated with ranibizumab) who had completed one of the three 2-year, randomized, controlled trials of monthly intravitreal ranibizumab treatment (MARINA, ANCHOR, or FOCUS trial). The patients had been treated with 0.3 or 0.5 mg of ranibizumab versus sham (MARINA) or 0.3 or 0.5 mg of ranibizumab versus photodynamic (PDT) (ANCHOR), and 0.5 mg of ranibizumab plus PDT with PDT alone (FOCUS).

Of 853 patients, 91% enrolled at 30 days or sooner after completing the initial trial. Of 600 initial ranibizumab-treated patients, 69% received injections a median 4 injections during 2 years in HORIZON. Two-year visual acuity (VA) data were available for 384 of the 600 patients (64%). These patients could receive 0.5-mg ranibizumab at 30-day or longer intervals as needed, according to Dr. Singer.

One case each of endophthalmitis, uveitis, and vitreous hemorrhage developed. There were no cases of retinal detachment, retinal tear, or lens damage. Any systemic adverse events were the same as those seen in the previous studies. Repeated injections were well tolerated.

“Of the patients who received initial treatment with ranibizumab during the ANCHOR, MARINA, and FOCUS trials, there was a mean 10.2-letter increase in VA during the first 2 years of the studies,” Dr. Singer said. “During the first year of the HORIZON study and the third year of the original trials, there was a 5.1-letter loss. At month 24 there was a 2-letter gain on an 8-letter loss from the start of the HORIZON trial.”

Among subjects with chronic lesions, those who crossed over and had not been exposed to ranibizumab previously, there were four times as many subjects who gained three lines of vision compared with those who received ranibizumab initially, Dr. Singer said.

“In the extension study, the initial VA increase decreased by a mean eight letters with less frequent dosing in years 3 and 4,” he concluded. “Delay in the initiation of treatment is associated with poor visual outcomes. Continued but less frequent dosing in years 3 and 4 was associated with visual decline.”