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Jump to Key Points Tarcocimab, a reformulated investigational biologic that combines a conjugated and unconjugated antibody protein, delivers sustained improvement in vision for patients with diabetic retinopathy after 1 year of treatment, according to the results of the phase 3 randomized controlled trial GLOW2.
“I think this drug is stronger than what we expected,” Margaret Chang, MD, MS, retina specialist in Sacramento, California, who reported the findings of the clinical trial at the American Academy of Ophthalmology (AAO) 2026 Annual Meeting in New Orleans.
Tarcocimab is an investigational anti-VEGF biologic consisting of 4 mg of an antibody biopolymer conjugate and 1 mg of an unconjugated free antibody for intravitreal injection into the eye. Chang said the addition of the latter makes tarcocimab “much less viscous” than its previous formulation.
The trial enrolled 255 patients with moderately severe nonproliferative diabetic retinopathy to mild proliferative diabetic retinopathy. The treatment group (n = 130) received an injection of 5 mg of tarcocimab on enrollment, at 4 and 8 weeks, and then again at 20 and 44 weeks.
- Tarcocimab: 62.5% achieved ≥2-step DRSS improvement at 48 weeks.
- Sham group: 3.3% reached ≥2-step DRSS improvement; P<.0001.
- Sight-threatening complications ↓ 85% vs sham: 2.4% vs 15.8%.
- DRSS benefit durable ≥6 months after 4th injection; minimal waning by 48 weeks.
- Visual acuity stable; ocular AEs similar between groups.
Trial Results
Among the treatment group, 62.5% of patients experienced at least a two-step improvement in the Diabetic Retinopathy Severity Scale (DRSS) at 48 weeks compared with 3.3% of patients in the sham group (P < .0001), Chang said.
The treatment group also had an 85% lower risk of developing a sight-threatening complication with an incidence of 2.4% vs 15.8% in the sham group (P = .0001), she said.
No patients taking tarcocimab had more than a two- or three-step worsening in the DRSS at week 48 compared with 13.1% with the former and 4.6% with the latter, respectively, of those in the sham arm, Chang said.
Further, 6 months after the fourth treatment, 59.3% of patients in the tarcocimab group experienced at least a two-step improvement in the DRSS. Four weeks later, at the 48-week mark, that percentage increased to 62.5%. Those results demonstrated the durability of the therapy, Chang said.
“One month later, there isn’t a significant change in DRSS improvement, suggesting that the efficacy of tarcocimab is at least 6 months or greater in this population,” she said.
Use of a GLP-1 receptor agonist did not appear to interfere with tarcocimab, Chang added; 60% vs 64.3% of GLP-1 users vs nonusers met the primary endpoint of at least a two-step improvement in DRSS at 48 weeks.
“There have been some studies that suggest that GLP-1s can be associated with initial worsening of diabetic retinopathy due to the rapid reduction of blood sugar,” Chang told Medscape Medical News. “Since so many of our patients are currently on or starting GLP-1s, it is reassuring that tarcocimab is still effective in these patients.”
Visual acuity remained stable through the study period in both groups, but patients taking tarcocimab experienced an 18.3-µm decrease in central subfield thickness, a key anatomic biomarker of retinal health, whereas those in the sham group showed a 6.7-µm increase. Both changes were considered slight, according to the GLOW2 researchers.
Furthermore, ocular adverse events were not appreciably different between the two groups, she said, with 29 and 34 patients in the tarcocimab and sham groups, respectively, reporting complications.
Drug Durability
The new formulation combines unconjugated free anti-VEGF antibodies with a large anti-VEGF antibody biopolymer conjugate that allows the anti-VEGF antibodies to persist in the vitreous for extended periods of time, leading to greater durability, Chang said. Tarcocimab has an average ocular half-life in humans of about 20 days, whereas faricimab has a half-life of 7.5 days, according to a 2024 analysis, she added.
Moreover, at the AAO 2026 Annual Meeting, Charles Wykoff, MD, PhD, chairman of research at Retina Consultants of Texas in Houston, reported the results of the DAYBREAK trial of tarcocimab in age-related macular degeneration. In that study, 54% of patients showed 6-month durability after a year.
“Although anti-VEGF treatments are very effective for our patients, the treatment burden is truly a problem that prevents many patients from obtaining optimal vision results in the real world,” Chang said.
The trial results show the potential of a treatment for diabetic retinopathy that has longer durability than existing anti-VEGF drugs, John Kitchens, MD, retina specialist in Lexington, Kentucky, told Medscape Medical News.
“Twice-yearly dosing with a better than 60% chance of a two-step improvement and not a single tarcocimab-treated eye worsening by two or more steps could finally make preventive treatment of diabetic retinopathy a reality,” Kitchens said.
Kodiak Sciences Inc. sponsored the trial. Chang is a consultant to Genentech and received grant support from Kodiak Sciences. Kitchens is a consultant to Genentech and Regeneron Pharmaceuticals.
Richard Mark Kirkner is a medical journalist based in the Philadelphia area.
