As reports of intraocular inflammation and vasculitis have cast caution onto the uptake of the newest approved anti-VEGF drug, Novartis’ Beovu (brolucizumab), the quest to build better mousetraps for treating exudative retinal disease proceeds unabated, as evidenced at this year’s Angiogenesis, Exudation and Degeneration conference. No fewer than eight candidates for treating exudative retinal disease are due to reach important milestones in their development this year. Here’s a review of what investigators reported there.
Brimo DDS (Allergan)
The Brimo DDS (for drug-delivery system) implant for geographic atrophy (GA) is moving forward with the Phase 3 IMAGINE and ENVISION trials, investigator Ryan Rich, MD, said. Brimo DDS uses the selective alpha2 adrenergic receptor bromonidine, long used for lowering intraocular pressure in glaucoma. The Phase 2A BEACON trial showed a reduction in GA progression in the treatment group compared with sham, with the difference maintained through the second year. A post-hoc analysis at 12 months showed a 32% reduction in GA progression.
KSI-301 (Kodiak Sciences)
Investigator Diana Do, MD, reported that pivotal studies of KSI-301 in retinal vein occlusion (RVO), diabetic macular edema (DME) and nonproliferative diabetic retinopathy (NPDR) are due to begin this year. KSI-301 is an intravitreal anti-VEGF antibody biopolymer conjugate. She provided updated Phase 1B data that showed 84% of eyes with neovascular age-related macular degeneration and 76% of DME eyes went 16 weeks or longer before needing retreatment (all eyes received three monthly loading doses).
Now that Opthea has completed the Phase 2b trial of OPT-302, investigator Pravin Dugel, MD, reported that the findings warrant moving onto Phase 3. OPT-302 is a fusion protein that targets vascular endothelial growth factor (VEGF) C and D, whereas Lucentis, with which OPT-302 has been paired in the Phase 2 trials, targets VEGF-A. Opthea reported last year the Phase 2B trial met its primary endpoint of demonstrating statistically significant superior gains in mean visual acuity at 24 weeks in patients treated with OPT-302 2 mg combination therapy with Lucentis vs. Lucentis monotherapy. Dr. Dugel noted that the inflammation in the 2-mg group was less than 1%. Opthea anticipates topline Phase 2A data later this year.
Aflibercept (Regeneron Pharmaceuticals)
Aflibercept was the subject of two presentations:
A pivotal trial in nAMD and a Phase 2 trial of the suprachoroidal drug-delivery platform are on deck for RGX-314 gene therapy for nAMD. Investigator Jeffrey S. Heier, MD, reported Phase 1/2A results that showed treated patients averaged 2.6 intravitreal injections over 12 months. In later cohorts, five of 12 and eight of 11 patients were free of intravitreal injections at six months.
The Phase 2 TOFU study of RBM-007 for nAMD enrolled its first patient days after the meeting. RBM-007 is an anti-FGF2 (fibroblast growth factor 2) RNA aptamer. Quan Dong Nguyen, MD, MS, reported the Phase 1/2A SUSHI dose-escalation study of a single intravitreal injection found the highest dose (2 mg) resulted in a reduction in subretinal fluid and subretinal hyper-reflective material on optical coherence tomography. Ribomic is based in Tokyo.
PDS with ranibizumab (Roche/Genentech)
The Port Delivery System with ranibizumab is the subject of two Phase 3 trials, investigator Carl Regillo, MD, reported: Archway in nAMD, which completed enrollment; and Pagoda in diabetic macular edema. PDS is a refillable implant designed to ease the treatment burden of monthly or bimonthly intravitreal injections of anti-VEGF agents. PDS with ranibizumab uses a 100 mg/mL concentration vs. 0.5 mg for Lucentis. The device is surgically implanted in the sclera and pars plana. Interim results have shown that 80% of patients who received the implant went six months or more before needing a refill and 60% went 12 months or longer; the median time to refill was 8.8 months, Dr. Regillo said.
Whether or not any of these products will make it to market (and be successful once there) remains the ultimate unknown. But in a week hit hard with bad news, there’s still a positive light shining in the retina development space.