Phase 2 signals for EyePoint’s vorolanib intravitreal insert include an approximately 88% reduction in treatment burden at six months in DME, with over 80% of patients supplement-free or requiring only one supplemental anti-VEGF injection. Across more than 190 patients treated in four trials, no serious ocular adverse events attributable to the insert have been reported. New in vitro data show greater than 50% reduction in IL-6 activity via JAK pathway inhibition, adding a mechanistic rationale beyond VEGF blockade that may align with the early and sustained gains observed in the VERONA study.
EyePoint has now detailed its pivotal DME program: two identical non-inferiority trials, COMO and CAPRI, each enrolling roughly 240 patients (both treatment-naïve and previously treated). Participants will be randomized on Day 1 to the vorolanib insert 2.7 mg with planned redosing every six months or to on-label aflibercept 2 mg. The primary endpoint is the blended change from baseline in BCVA at weeks 52 and 56. First patient dosing is anticipated in the first quarter of 2026. The design mirrors the company’s ongoing Phase 3 wet AMD program, which is also testing six-month redosing against the standard of care.
Strategically, the company is pursuing a pragmatic non-inferiority path that prioritizes durability and operational simplicity over superiority claims. Positioning the product as a six-month TKI-based insert with potential multi-mechanism activity aims to differentiate it from short-acting anti-VEGF agents and from more complex delivery systems that have faced safety and adoption hurdles. The choice of aflibercept 2 mg as a comparator aligns with a well-trodden regulatory route but invites a commercial relevance question as Eylea HD 8 mg and faricimab continue to extend dosing intervals in practice. The IL-6/JAK story is mechanistically appealing in a multifactorial disease, but it remains preclinical; regulators will focus on clinical readouts for rescue rates, durability, and inflammation control.
For research sites, the insert could lower visit cadence and injection volume if the six-month schedule holds, while introducing procedure and handling workflows specific to a bioerodible intravitreal device. The inclusion of both naïve and previously treated patients broadens referral pathways and may ease recruitment, though heterogeneity could complicate subgroup analyses. CROs and sponsors operating in retinal trials should note a moderate sample size and duplicated trial architecture that can accelerate enrollment if site networks are already primed from wet AMD studies. Safety monitoring will need to be attentive to intraocular inflammation, ocular hypertension, and any JAK-related signals, even if systemic exposure is minimal. Payers will ultimately weigh durability and clinic throughput against device cost and the need for supplemental injections.
Key watch items are executional and regulatory. Site start-up and geographic breadth will determine whether first-patient timing slips into mid-2026 amid competition for DME patients. The clinical relevance of the comparator, the rescue injection algorithm, and real-world-like retreatment criteria will heavily influence payer and physician adoption. Manufacturing readiness for a preloaded, sterile bioerodible insert is a nontrivial dependency, particularly given the company’s prior regulatory scrutiny of its facility. Near-term catalysts include mid-2026 wet AMD Phase 3 data and early enrollment metrics for DME. If Phase 3 replicates VERONA’s signal with acceptable safety and low rescue use, the insert could establish a durable foothold; if not, the field’s pivot toward longer-interval biologics may narrow its window.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
