Virtual ASRS Reporter’s Notebook

The American Society of Retina Specialists annual scientific meeting went virtual this year, but that didn’t diminish the multitude of reports on retina treatments in various stages of the development pipeline. Here we present some notable readouts of trials in exudative retinal disease with this caveat: This is by no means a comprehensive list.

Potential Geographic Atrophy Treatments

Treatments for geographic atrophy (GA) – the vision-debilitating disease secondary to dry age-related macular degeneration (AMD) – has drawn a lot of attention from drug developers because no cure exists. Two investigators reported on advances in clinical trials for emerging treatments.

Barruch D. Kupperman, MD, PhD, reported that the complement C5 inhibitor avacincaptad pegol (Zimura, IVERIC bio) resulted in a 27.38% reduction in the rate of GA growth over 12 months in 286 patients enrolled in the GATHER1 pivotal clinical trial. He noted that this showed that complement C5 is a viable target to prevent or slow the death of retinal pigment epithelium cells in patients with GA.

Results of a Phase I safety study of intravitreal aHtrA1 (Genentech/Roche) – a novel serine protease inhibitor known as anti-high temperature requirement A1 – showed the drug was well tolerated in single doses up to 20 mg and three monthly doses of 20 mg, reported W. Zachery Bridges Jr., MD. He noted a Phase II study evaluating the drug’s efficacy is in progress.

Disclosures: Dr. Kupperman has no relevant relationships to disclose. Dr. Bridges disclosed relationships with Genentech/Roche.

Sources: Kupperman BD. Avacincaptad pegol, a novel C5 inhibitor, reached statistical significance in a pivotal clinical trial for geographic atrophy secondary to dry AMD; Bridges WZ, et al. Phase 1 safety study of intravitreal (ITV) anti-high temperature requirement A1 (aHtrA1), a novel serine protease inhibitor, in patients with GA.

OPT-302 Proof-of-Concept Trial

David A. Boyer, MD, reported that a proof-of-concept trial of OPT-302 (Opthea) for treatment of diabetic macular edema (DME) in patients who failed on previous anti-VEGF treatments showed the drug was well tolerated and improved visual and anatomical outcomes. In the Phase Ib trial, patients received escalating doses of OPT-302 (0.3, 1, or 2 mg) along with aflibercept 2 mg (Eylea, Regeneron Pharmaceuticals) in three cohorts. The study assessed safety, vision, and anatomical outcomes of patients switched from anti-VEGF-A monotherapy to combination OPT-302 and aflibercept for persistent DME. OPT-302 inhibits VEGF-C/-D, which may contribute to treatment resistance with VEGF-A suppression.

Interim analysis showed best-corrected visual acuity (BCVA) at week 12 improved by a mean of 7.7 letters (95% CI: 2, 13.3) from baseline, and a dose-response relationship of improved BCVA with increasing doses of OPT-302 and aflibercept. As for anatomical outcomes, Dr. Boyer reported a reduction in central retinal subfield thickness at week 12, and six of nine patients had a greater than 50% reduction in excess foveal thickness as measured on spectral-domain optical coherence tomography (SD-OCT).

Disclosures: Dr. Boyer disclosed financial relationships with Regeneron Pharmaceuticals and Genentech/Roche.

Source: Boyer D. Switching to combination OPT-302 with aflibercept from prior anti-VEGF-A monotherapy in eyes with persistent diabetic macula edema (DME).

Port Delivery System Phase II, III Results

The Port Delivery System with ranibizumab (PDS, (Genentech/Roche), a refillable ocular implant for the treatment of wet AMD, was the subject of two prerecorded ASRS presentations: Peter A. Campochiaro, MD, presented top-line results from the Phase III Archway trial; and David A. Eichenbaum, MD, reported end-of-study results from the Phase II Ladder trial.

In Archway, 98.4% of PDS patients went six months without needing additional treatment, and achieved vision outcomes as good as patients receiving monthly ranibizumab (Lucentis) injections. The implant was generally well tolerated with a favorable benefit-risk profile, Dr. Campochiaro said.

Ladder evaluated three different doses of ranibizumab in the PDS: 10, 40, and 100 mg/mL. The trial compared those patients with a group on monthly intravitreal Lucentis therapy. Dr. Eichenbaum said PDS 100 mg/mL continuously maintained vision and anatomical outcomes through the 22 months of the study. The median time to the first refill in the 100-mg/mL arm was 15.8 months, and improvement in BCVA and central foveal thickness (CFT) were similar between the 100-mg/mL PDS and monthly treatment arms.

Disclosures: Dr. Campochiaro disclosed financial relationships with Allergan, Genentech, Novartis, and Regeneron Pharmaceuticals. Dr. Eichenbaum disclosed financial relationships with Novartis, Allergan, Genentech, and Regeneron Pharmaceuticals.

Sources: Campochiaro PA, et al. Primary analysis results of the Phase 3 Archway trial of the Port Delivery System with ranibizumab (PDS) for patients with neovascular AMD; Eichenbaum DA, et al. Ladder Phase 2 trial of the Port Delivery System with ranibizumab (PDS) end of study results.

Faricimab Phase II Results

Another wet AMD candidate in the Genentech/Roche pipeline is faricimab, the first bispecific antibody that targets two disease pathways: angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A). Carl J. Danzig, MD, reported on results of the Phase II STAIRWAY trial to assess the drug’s durability. Dosed at extended 16-week flex and 12-week fixed intervals, faricimab provided sustained anatomical and visual outcomes comparable to monthly Lucentis over a year in patients who had no previous treatment for AMD. Anatomical changes were measured by SD-OCT and fluorescein angiography. Vision and macular anatomy were maintained with approximately half as many injections of faricimab on the 16-week flex or 12-week fixed versus Lucentis monthly dosing.

Disclosure: Dr. Danzig has no commercial interests to disclose.

Source: Danzig CJ, et al. Clinical effects of blocking Ang-2 and VEGF with faricimab in the Phase 2 STAIRWAY Trial.

Abicipar Still Focus of Readouts

Despite AbbVie’s setback with abicipar pegol from the US Food and Drug Administration Complete Response Letter essentially rejecting the drug because of issues with intraocular inflammation, no fewer than four prerecorded ASRS presentations reported on trials evaluating the wet AMD treatment.

Tarak S. Hassan, MD, presented a first-time report on inflammation in 11 eyes that exited the Phase II Maple Trial. He noted the overall rate of inflammation was 8.9% in the study eyes (11/123). Inflammation was diagnosed after one injection in three eyes, after two injections in two eyes, and after four injections in six eyes. Nine cases were mild or moderate in severity. Severe inflammation was diagnosed as one case each of iritis and uveitis.

All 11 patients received treatment with topical corticosteroids, and four with moderate and/or severe inflammation were also given oral or intraocular steroids. All the cases resolved after the study and intraocular pressure returned to normal.

Three other presentations focused on results from the Phase III CEDAR and SEQUOIA trials of abicipar: Nancy M. Holekamp, MD, reported on two-year results of abicipar versus Lucentis; Peter K. Kaiser, MD, reported on two-year model simulations of visual outcomes; and Jeremy D. Wolfe, MD, MS, presented results of anatomical changes in the retina and visual acuity outcomes after 52 weeks.

Disclosures: Dr. Hassan disclosed relationships with Allergan, Genentech/Roche, Novartis, and Regeneron Pharmaceuticals.

Source: Hassan TS. Abicipar Phase 2 MAPLE trial: Evaluation of all patients with post-injection inflammation.