EyeArt AI System Receives EU Approval for AMD and Glaucoma Screening

■ Eyenuk, a global artificial intelligence (AI) digital health company, has been approved to market its EyeArt AI eye screening system in the European Union for detection of age-related macular degeneration (AMD) and glaucomatous optic nerve damage, a sign of glaucoma. The EU had previously approved EyeArt AI for the detection of diabetic retinopathy (DR) and diabetic macular edema (DME).

The EyeArt AI system is integrated with retinal imaging cameras and can be operated by clinical support staff to provide fully autonomous screening for diabetic retinopathy, AMD, and glaucomatous optic nerve damage during a patient’s regular exam. Once the patient’s fundus images have been uploaded to the EyeArt AI system, the detection results are available in a PDF report in less than 30 seconds. The US Food and Drug Administration (FDA) has approved the device for detection of diabetic retinopathy.

“DR, AMD, and glaucoma are all asymptomatic in their early stages. The high sensitivity of the EyeArt AI system, and its ability to be delivered without a specialist, makes it easier to catch the diseases early and to take preventative measures to protect the vision of these patients,” said Kaushal Solanki, founder and CEO of Eyenuk, in a news release. “Our autonomous AI can now help many more patients at risk of vision loss—the population at risk of AMD and glaucoma, particularly seniors, in addition to people with diabetes.”

ZETA-1 Trial Data Indicates APX3330 May Slow Progression of Diabetic Retinopathy

■ Ocuphire Pharma announced topline efficacy and safety results from its ZETA-1 trial evaluating oral APX3330 for the treatment of diabetic retinopathy (DR) on January 25, 2023. The data indicated that APX3330 can potentially slow disease progression while demonstrating a favorable safety profile in diabetic patients.

ZETA-1 was a randomized, double-masked, placebo-controlled phase 2 trial designed to evaluate the efficacy and safety of APX3330 in 103 patients with at least one eye meeting criteria for moderately severe to severe non-proliferative diabetic retinopathy (NPDR) or mild proliferative DR (mild PDR). The ETDRS diabetic retinopathy severity scale (DRSS) is a categorical tool for clinical trials that contains 10 discreet steps, from no retinopathy to severe proliferative retinopathy, derived from the grading of fundus photographs for each eye at a central reading center. Each patient’s study eye had a baseline DRSS step of 5, 6 or 7. The patients were randomized to receive 600 mg APX3330 or placebo daily (BID) over 24 weeks. Primary and secondary endpoints evaluated +/- 1, 2, 3, and 4 step improvement and worsening in DRSS at week 12 and week 24, change in best-corrected visual acuity (BCVA), change in central subfield thickness (CST), and safety and tolerability.

APX3330 did not meet the primary endpoint (% of patients with a ≥2-step improvement in DRSS at week 24 in the study eye). Given the oral systemic delivery of APX3330, however, it is important to evaluate the effect on both eyes. A potential phase 3 registration primary endpoint is a ≥3-step worsening of DRSS as a composite of both eyes (binocular). This secondary endpoint was prespecified and evaluated in the ZETA-1 trial. APX3330 demonstrated statistically significant reduction of disease progression at 24 weeks: No (0%) APX3330-treated patients had a binocular ≥3-step worsening of DRSS from baseline compared with 16% for placebo-treated patients (P=0.04). This endpoint is the planned phase 3 primary endpoint for future registration trials that will be confirmed at the end of phase 2 meeting with the FDA.

Additional efficacy endpoints were directionally favorable to support the effect of APX3330 in slowing the progression of DR and preserving vision. Visual acuity was stable with APX3330 and a trend was seen with fewer APX3330 treated patients losing 5 or more letters of distance vision compared to placebo patients (6% vs 19%, P=0.07). APX3330 showed a favorable safety and tolerability profile. Treatment-related adverse events were uncommon, and most were mild in severity. There were no treatment-related serious adverse events.

“I am very encouraged by the data from ZETA-1 showing that APX3330 can potentially slow disease progression,” Peter K. Kaiser, MD, professor of ophthalmology at the Cole Eye Institute of the Cleveland Clinic Foundation, said in a news release. “If these results are confirmed in phase 3 and APX3330 is subsequently approved, healthcare providers would have an important new primary preventative therapeutic option that could be used in a large number of patients who are earlier in the course of disease. This would potentially reduce the number of patients who experience devastating vision loss.”

Analysis of the trial data is ongoing. Detailed results will be presented at multiple medical meetings, including Angiogenesis, Exudation and Degeneration (virtual seminar, February 10-11, 2023) and the Macula Society’s 46th Annual Meeting (Miami Beach, Florida, February 15-18, 2023). The data will also be submitted for peer review publication in 2023.

Frontera Begins Gene Therapy Trials

■ Frontera Therapeutics has begun phase 1 clinical trials of 2 gene therapy products at the Ophthalmology Hospital of Tianjin Medical University in Tianjin, China, the company announced on February 2, 2023. FT-001 is a gene therapy product that targets inherited retinal degenerations (IRDs) with a RPE65 mutation. FT-003 is being studied for the treatment of neovascular (wet) age-related macular degeneration (wAMD).

“I am excited by the momentum the Frontera team has achieved so far this year with the dosing of the first patients in two gene therapy phase 1 clinical trials during the month of January for FT-001 and FT-003,” said Yong Dai, PhD, the founder and CEO of Frontera. He expects to have initial clinical results for both FT-001 and FT-003 later this year.

OASIS Extension Study Reports Positive Data

■ Clearside Biomedical has announced positive results from the extension study of its OASIS phase 1/2a clinical trial of CLS-AX (axitinib injectable suspension) administered by suprachoroidal injection via Clearside’s SCS Microinjector in neovascular (wet) age-related macular degeneration (wAMD) participants. These results include the final six-month data from all participants in the extension study and augment the previously reported 3-month results and interim extension data.

“The positive data from our OASIS extension study reinforces our belief that CLS-AX has the potential to reduce treatment burden in patients with wet AMD while maintaining stable visual acuity,” Thomas A. Ciulla, MD, MBA, the chief medical officer and chief development officer of Clearside Biomedical, said in a news release. “In all participants in the trial, CLS-AX was well tolerated and demonstrated an excellent safety profile across all timepoints and doses. Importantly, the full extension data reported today showed promising durability with 67% of participants going at least six months without additional treatment, and 50% of participants going beyond six months. With these favorable data, we are actively preparing for and expect to initiate a randomized, controlled, double-masked, phase 2b clinical trial, called ODYSSEY, in the first quarter of this year, with the primary endpoint readout anticipated in mid-2024.”