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CHICAGO -- A novel antibody-biopolymer conjugate (ABC) achieved visual acuity comparable to aflibercept (Eylea) for retinal vein occlusion (RVO) with less frequent dosing, according to a randomized trial reported here.

Best-corrected visual acuity (BCVA) in patients with branch RVO (BRVO) improved by 14.2 letters at 24 weeks with tarcocimab dosed every 8 weeks, which met statistical criteria for noninferiority to the 15.6-letter improvement with aflibercept every 4 weeks. Change in retinal thickness (CST) did not differ significantly between tarcocimab and aflibercept. A hierarchical analysis of all RVO (central [CRVO] and BRVO) also demonstrated noninferiority of tarcocimab to aflibercept, as reported at the American Academy of Ophthalmology (AAO) meeting.

"Tarcocimab is the first anti-VEGF therapy to show comparable visual acuity outcomes to monthly aflibercept while doubling the treatment interval," said Michael Singer, MD, of UT Health San Antonio and Medical Center Ophthalmology Associates. "During the matched phase [baseline to week 8], strong efficacy was observed with comparable vision and anatomic improvement as early as week 1. During the maintenance phase, the [CST] and visual gains were similar with half the number of doses. The safety profile was favorable with low rates of intraocular inflammation and no cases of endophthalmitis or vascular occlusion."

"The successful outcomes from this study lend confidence to the ongoing trials in wet AMD [age-related macular degeneration], DME [diabetic macular edema], and non-PDR [proliferative diabetic retinopathy]," Singer added.

New-Generation Anti-VEGF

Tarcocimab represents a new generation of VEGF-targeted therapies for retinal diseases, consisting of an anti-VEGF monoclonal antibody linked to a high molecular weight phosphorylcholine polymer to increase durability and efficacy. The construct blocks all VEGF-A isoforms, said Singer.

In a phase Ib trial including patients with AMD, DME, and RVO, tarcocimab led to early and sustained improvement in vision and reductions in retinal thickening. The results supported continued investigation in advanced-phase trials, including the randomized phase III in patients with RVO.

Eligible patients had untreated RVO (BRVO or CRVO), BCVA of 80 to 25 letters, and CST ≥320 µm. Participants were randomized to aflibercept once every 4 weeks or to tarcocimab administered at baseline, week 4, and then every 8 weeks. At 24 weeks patients in each arm switched to individualized dosing to month 12, followed by individualized open-label dosing of tarcocimab for all patients during months 12-18.

The primary endpoint was mean change in BCVA at week 24. Investigators performed a hierarchical test for noninferiority in patients with BRVO and then in those with BRVO and CRVO if noninferiority was achieved in the initial analysis.

Data analysis included 568 randomized patients. About 77% of patients had BRVO, baseline BCVA averaged about 60 letters (a majority in the range of 50-69 letters), baseline mean CST was 570-590 µm, and about 90% of the patients had a disease duration of less than 3 months.

Key Findings

The trial met the primary endpoint of noninferiority in the BRVO subgroup at 24 weeks (P=0.0004). Reduction in CST averaged 269.3 µm with aflibercept and 253.8 with tarcocimab, which also met criteria for noninferiority. The analysis of all patients with RVO showed mean BCVA improvement at 24 weeks of 13.0 letters with tarcocimab versus 15.5 with aflibercept (P=0.0243 for noninferiority), and mean CST reduction of 278.4 versus 315.5 µm.

In the BRVO subgroup and all patients, tarcocimab and aflibercept had similar effects on BCVA and CST in both the matched and maintenance phases of the study. Similar proportions of patients gained at least 15 letters and almost all patients in both treatment groups avoided BCVA loss of 15 or more letters. Additionally, a similar number of patients treated with tarcocimab or aflibercept achieved good vision (≥20/40) and avoided poor vision (≤20/200) at week 24.

Tarcocimab achieved similar results with an average of 3.9 injections versus 5.8 for aflibercept, said Singer.

Ocular adverse events (AEs) occurred slightly more often with tarcocimab (30.3% vs 25.0%), including serious ocular AEs in 1.4% vs 0%. Non-ocular AEs occurred in 43.3% versus 38.0%, including serious non-ocular AEs in 5.3% of each treatment arm. Intraocular inflammation occurred in 1.4% of patients in the tarcocimab arm and 0.4% with aflibercept. No patient in either treatment group developed endophthalmitis up to week 24.

The practical implications of the findings were reflected in a of tarcocimab and aflibercept in patients with DME. The primary finding was that decreased frequency of treatment was associated with decreased improvement in visual acuity.

"If we're able to decrease the treatment burden from six doses to four doses and maintain visual outcomes, that's really meaningful for our patients," said Singer. "Tarcocimab is the first anti-VEGF therapy to demonstrate comparable visual gains while doubling the treatment interval from monthly to every-other-month dosing."

Calling the results "very impressive," AAO discussion panelist Eleonora Lad, MD, PhD, of Duke University Medical Center in Durham, North Carolina, asked how tarcocimab might fit into clinical practice.

"Have you looked at patients with ischemic versus non-ischemic RVOs?" she asked. "Would you still use laser? How would you change your management should this drug be approved?"

Singer said the data related to ischemic versus non-ischemic RVO have yet to be analyzed. The implications for clinical practice are clearer.

"Right now, if we treat people on label for either branch or central retinal vein occlusion, we have to give continuous shots," he said. "Having something we can give every other month is pretty exciting because we all know that life is messy. If we're able to give fewer shots and keep the great vision, that makes me feel better."

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