AMD trial data are highlights at recent conferences

By Michelle Dalton, ELS

Clinical trial data focusing on treatment for age-related macular degeneration (AMD) have been a highlight at many recent ophthalmology meetings. Here are a few of the latest clinical trials that physicians need to be aware.

Proxima A analysis for GA

Proxima A, prospective, observational, multicenter study involving 91 global sites designed to better understand the natural disease progression of bilateral geographic atrophy (GA), found severe functional impact of GA on patients and the high rate of functional deterioration over time.

Data was presented during the 15th Annual Angiogenesis, Exudation, and Degeneration Meeting. Proxima A enrolled 296 patients; the mean patient age was 77 years, and the majority of patients enrolled on trial were white and female.

At 12 months, mean change in GA lesion size was +2.08 from baseline, said Nancy M. Holecamp, MD. Baseline lesion size ≥4-disc area and non-subfoveal baseline lesion location were associated with higher GA lesion progression rates.

Patients lost an average of 6 letters from baseline at 12 months, and maximum reading speeds decreased as well. Monocular maximum reading speed decreased by 15 wpm while binocular maximum reading speed decreased by 19 wpm.

These data demonstrate the significant toll GA takes on vision overtime, with a high rate of functional deterioration consistent across end points. Researchers concluded that further research is needed to fully understand natural history and disease progression of GA.

Carotuximab for wet AMD

Santen presented topline results from the phase I/II study of DE-122 (carotuximab) for refractory wet AMD. Carotuximab is a novel antibody to endoglin, a protein overexpressed on endothelium essential for angiogenesis and upregulated by anti-VEGF.

The study assessed the safety, tolerability, and bioactivity of a single intravitreal injection of carotuximab at 4 dose levels in 12 patients. Three patients were randomly assigned per dose level and followed for up to 3 months.

The drug appears to be well tolerated. Researchers reported no serious adverse events with any level of carotuximab dosing. Data also suggested bioactivity of the drug in patients with neovascular AMD as measured by mean change in central subfield thickness (CST) based on the spectral domain optical coherence tomography.

Study investigator Victor H. Gonzalez, MD, called the results “very encouraging” and “support the ongoing clinical development of DE-122 as a potential treatment for patients with wet AMD.”

CNV subtypes/subretinal fibrosis

A post-hoc analysis of the HARBOR trial, presented during the 2017 American Academy of Ophthalmology (AAO) meeting, sought to determine if certain subtypes of choroidal neovascularization (CNV) gave patients with neovascular AMD an increased risk for subretinal fibrosis.¹

HARBOR, which enrolled 1,097 patients with wet AMD, was a 2-year, phase III, multicenter trial that evaluated ranibizumab 0.5 mg and 2.0 mg administered monthly or PRN after 3 monthly loading doses.

In the post-hoc analysis, researchers examined the presence of fibrosis by baseline CNV lesion subtype and visual acuity outcomes in patients with and without detectable fibrosis using fluorescein angiography and red-free fundus photography.

Most patients in HARBOR had minimally classic CNV (46.4%, n = 509) or occult CNV (38.1%, n = 418) at baseline; 15.5% (n = 170) of patients had predominantly classic CNV. Patients were excluded from HARBOR if fibrosis was detected during initial screening.

Researchers found that at 2 years, fibrosis was detected in 78% of patients with predominantly classic lesions, 51% of patients with minimally classic lesions, and 20% of patients with occult lesions at baseline (P < 0.001).

Visual gains (≥ 15 letters) occurred at 2 years regardless of fibrosis detection. Study authors concluded that the association between baseline lesion subtypes may be useful in informing future clinical trial designs.

Tx despite meeting switch criteria

In another subanalysis of HARBOR, also presented at the 2017 AAO meeting, researchers explored the clinical impact on patients with wet AMD who continued with their original therapy despite meeting switch criteria.

Month 3 switchers had to receive all initial doses of monthly ranibizumab, while month 6 switchers had to have at least 5 of 6 initial doses of monthly ranibizumab. Patients could switch therapies if they had a ≤ 5-letter gain from baseline, visual acuity of 20/40 or worse, or intraretinal or subretinal fluid with central foveal thickness (CFT) greater than CST.

At 3 months, 44 patients (4.2%, 1,059 eligible patients) did not switch treatments despite meeting the criteria, while that number was 37 patients (4.8%, 769 eligible patients) at 6 months.

Researchers found that patients who met switch criteria at 3 months continued to demonstrate visual gains (mean change in visual acuity at 12 months, 5.3 letters) and anatomic improvements (mean change in CFT at 12 months, −92.5 μm).

Visual gains were not quite as robust for month 6 switchers (mean change in visual acuity at 12 months, 1.6 letters), however, the anatomic improvements were similar (mean change in CFT at 12 months, −99.6 μm).

Reference

1. Ho AC, Busbee BG, Regillo CD, et al. Twenty-Four-Month Efficacy and Safety of 0.5 mg or 2.0 mg Ranibizumab in Patients with Subfoveal Neovascular Age-Related Macular Degeneration. Ophthalmology;121(11):2181-92.