OLN324 shows comparable vision gains, potential durability advantage vs faricimab in phase 1b wAMD, DME study

A phase 1b randomized, head-to-head study suggests that the investigational VEGF/Ang2 bispecific antibody OLN324 may offer comparable or improved anatomic and functional outcomes relative to faricimab in patients with neovascular age-related macular degeneration (wAMD) and diabetic macular edema (DME), according to 20-week data released by the sponsor.¹ The findings, while preliminary, highlight ongoing efforts to extend durability and improve anatomic responses beyond current anti-VEGF–based standards of care.

In the JADE trial, OLN324 demonstrated numerically greater visual acuity gains and evidence of sustained retinal drying with fewer retreatments during a treatment-free follow-up period, compared with faricimab.¹ However, the study was not powered for definitive efficacy comparisons, and results remain exploratory pending peer-reviewed publication and larger phase 3 trials.

Trial overview and key findings

JADE is a randomized, US-based phase 1b study enrolling 164 patients with either DME or wAMD. Participants received three monthly intravitreal injections of OLN324 (2 mg or 4 mg) or faricimab (6 mg), followed by a 12-week observation period with retreatment permitted based on prespecified criteria.¹

The primary objective was safety and tolerability, with exploratory efficacy endpoints including best-corrected visual acuity (BCVA) and optical coherence tomography (OCT)–based anatomic measures.¹

At week 20, patients with DME treated with OLN324 4 mg showed greater reductions in central subfield thickness compared with faricimab, along with numerically greater visual gains.¹ A higher proportion of OLN324-treated patients completed the 12-week off-treatment period without retreatment (93% vs 89%).¹

In wAMD, both groups achieved similar reductions in retinal thickness through week 12, which were maintained to week 20.¹ BCVA improvements were numerically greater with OLN324, with a reported mean difference of +2.2 letters at week 20.¹ Retreatment rates were similar between groups (82% vs 81%).¹

Newly reported analyses also suggested greater reductions in pigment epithelial detachment (PED) thickness with OLN324 compared with faricimab at week 12, with durability through week 20.¹ Persistent PEDs are associated with fibrosis and long-term visual decline, representing an ongoing therapeutic challenge in wAMD.²

No cases of intraocular inflammation, retinal vasculitis, or occlusive retinal vasculitis were reported in the OLN324 arms through 20 weeks; one case of intraocular inflammation occurred in the faricimab group.¹ The small sample size and short follow-up limit conclusions about comparative safety.

Clinical context

Anti-VEGF therapy remains the cornerstone of treatment for both wAMD and DME, with agents such as aflibercept, ranibizumab, and faricimab demonstrating efficacy in reducing retinal fluid and improving vision.³⁻⁵ Faricimab, a bispecific antibody targeting both VEGF-A and angiopoietin-2 (Ang2), was approved based on phase 3 TENAYA/LUCERNE and YOSEMITE/RHINE trials, which demonstrated extended dosing intervals in some patients.⁴^,⁵

Despite these advances, treatment burden and incomplete anatomic responses—particularly persistent fluid and PEDs—remain unmet needs.³ Dual-pathway inhibition of VEGF and Ang2 is intended to improve vascular stability and reduce leakage and inflammation, though the magnitude of incremental benefit over VEGF inhibition alone continues to be evaluated.⁴

Drug background

OLN324 is an investigational, next-generation bispecific antibody targeting VEGF and Ang2.¹ According to the sponsor, it is engineered with higher Ang2 binding potency, a smaller molecular format, and higher molar dosing compared with currently approved agents.¹ These design features are hypothesized to enhance tissue penetration and durability, although clinical validation is ongoing.

Interpretation and limitations

The JADE study provides early comparative data suggesting that intensified Ang2 inhibition may influence anatomic outcomes such as PED resolution and retinal drying. However, several limitations warrant caution.

First, the trial was a phase 1b study with a relatively small sample size and exploratory efficacy endpoints.¹ The study was not powered to detect statistically significant differences in visual acuity or retreatment rates. Second, follow-up was limited to 20 weeks, precluding assessment of long-term durability and safety. Third, results have not yet been published in a peer-reviewed journal, and detailed subgroup analyses are not available.

Additionally, while OCT-based anatomic improvements are clinically relevant, their translation into sustained visual benefit remains variable across studies.³

Next steps

The sponsor has indicated plans to initiate global phase 3 trials in both DME and wAMD.¹ These studies will be necessary to determine whether the observed trends translate into clinically meaningful improvements in vision, treatment burden, and long-term safety relative to established therapies.

References

1. Ollin Biosciences. Ollin announces final data from randomized head-to-head study of OLN324 compared to faricimab in wAMD and DME. Business Wire. March 27, 2026. Accessed March 30, 2026. https://www.businesswire.com/news/home/20260327639180/en/Ollin-Biosciences-Announces-Final-Data-From-Randomized-Head-to-Head-Study-of-OLN324-Compared-to-Faricimab-Vabysmo-in-Wet-Age-Related-Macular-Degeneration-and-Diabetic-Macular-Edema

2. Schmidt-Erfurth U, et al. Guidelines for the management of neovascular age-related macular degeneration. Prog Retin Eye Res. 2014;40:1-26. https://doi.org/10.1016/j.preteyeres.2014.02.001

3. Wykoff CC, et al. Optimizing anti-VEGF treatment outcomes for patients with neovascular AMD. Am J Ophthalmol. 2022;234:1-13. https://doi.org/10.1016/j.ajo.2021.07.014

4. Heier JS, et al. Efficacy, durability, and safety of faricimab in neovascular age-related macular degeneration (TENAYA and LUCERNE). Lancet. 2022;399(10326):729-740. https://doi.org/10.1016/S0140-6736(22)00010-1

5. Wykoff CC, et al. Faricimab in diabetic macular edema (YOSEMITE and RHINE). Lancet. 2022;399(10326):741-755. https://doi.org/10.1016/S0140-6736(22)00018-6