Combined complement inhibitor, anti-VEGF may be safe for treatment of wet AMD

FORT LAUDERDALE, Fla. — Intravitreal injection of an anti-VEGF agent combined with a complement inhibitor was safe and well-tolerated in patients treated for age-related macular degeneration, a speaker said here.

Scott W. Cousins, MD, presented results of a phase 1 study at the Association for Research in Vision and Ophthalmology meeting that was designed to assess the safety and tolerability of the aptamer ARC1905, a complement factor 5 inhibitor (Ophthotech) combined with Lucentis (ranibizumab, Genentech).

Study results strongly suggested a link between complement activity and neovascular AMD and dry AMD, Dr. Cousins said.

“We conclude that the drug is safe, well-tolerated, and the phase 1 results indicate that a randomized controlled trial is warranted and that is being planned,” he said. “Not only is the drug well-tolerated, but there is a suggestion in some cases of potential drusen regression.”

ARC1905 prevents the enzymatic cleavage of intact C5 into two active products, C5a and C5b, Dr. Cousins said.

Treatment of wet AMD

The prospective, open-label, dose-escalating, non-controlled, multicenter study was designed to test the safety of intravitreal injections of ARC1905 combined with ranibizumab in patients with neovascular AMD. It included 58 patients with all clinical subtypes of subfoveal neovascular AMD.

Key inclusion criteria were subfoveal choroidal neovascularization and AMD, any lesion subtype, lesion size less than five disc areas and visual acuity of 20/63 to 20/200.

Primary endpoints were dosing and toxicity. Secondary endpoints were visual acuity, optical coherence tomography measurements of central foveal thickness and other outcome measures.

Patients received three to six monthly injections of 0.03 mg, 0.3 mg, 1 mg or 2 mg of ARC1905 in conjunction with 0.5 mg of ranibizumab. Outcomes were evaluated 4 weeks after final dosing.

“Study results showed that increased dosing was safe and tolerable for all patients,” Dr. Cousins said. “In addition, patients with less initial foveal thickness regained better vision.”

Data showed that 60% of patients who received ARC1905 with 2-mg injections of ranibizumab gained three or more lines of vision, Dr. Cousins said.

“Not surprisingly, the OCT thickness dramatically reduced during the course of this study,” he said. “Results showed that eyes with thinner initial OCTs showed a better visual acuity gain than those that started with a thicker OCT. It would suggest, or at least raise a hypothesis, that antipermeability effects may not be the only driver of visual improvement, that maybe we’re blocking the inflammatory contribution to vision loss.”

The only adverse effect was a single patient with posterior subcapsular cataract formation, Dr. Cousins said.

Clinical trial for dry AMD

An unexpected preliminary finding from the study suggested that ARC1905 also caused drusen regression in some of the patients, Dr. Cousins told Ocular Surgery News. Previous research by others has shown a strong correlation between complement and drusen formation, the hallmark of dry AMD.

Ophthotech is conducting a trial of ARC1905 in non-neovascular AMD. Results are expected next year, Dr. Cousins said. – by Matt Hasson

• Scott. W. Cousins, MD, can be reached at Duke University Eye Center, DUMC Box 3802, Durham, NC 27710; 919-684-3090; fax: 919-681-6474; e-mail: scott.cousins@duke.edu.