Novel TKI Insert Shows Promise in DME Treatment

Results of the VERONA phase II trial show the in-office administered vorolanib intravitreal insert (DURAVYU™) has the potential to substantially reduce treatment burden for patients with diabetic macular edema (DME) relative to current anti-VEGF treatment (2).

Vorolanib is a selective tyrosine kinase inhibitor (TKI) that inhibits VEGF receptors 1, 2, and 3 and the PDGFR (2). The investigational therapy uses a proprietary bioerodible matrix (Durasert E™) that releases vorolanib immediately upon insertion and continuously for at least six months (2-4).

VERONA is a 24-week, single-masked, open-label trial that randomized 27 patients 2:2:1 to receive a single injection of aflibercept 2.0 mg plus either DURAVYU 2.7 mg, DURAVYU 1.3 mg, or aflibercept alone (control arm). Patients returned for follow-up every 4 weeks and received supplemental aflibercept 2.0 mg injections based on prespecified criteria or investigator discretion.

VERONA met its primary endpoint, showing that both DURAVYU doses extended the time to first supplemental anti-VEGF injection compared to aflibercept control. Up to week 24, 73 percent and 60 percent of patients in the DURAVYU 2.7 mg and 1.3 mg groups, respectively, did not require supplemental aflibercept injections compared with 50 percent of patients in the aflibercept control arm.

Analyses of secondary endpoints showed clinically meaningful functional and anatomical improvements occurred early in the DURAVYU groups and were sustained to week 24. At week 24, BCVA was similar amongst all treatment arms; however, the DURVAYU 2.7mg dose demonstrated more anatomical control and better drying. From baseline to week 4, eyes that received the higher dose vorolanib intravitreal insert had a mean BCVA gain of 7 letters, and central subfield thickness (CST) in this group decreased by a mean of 90.3 µm. The early improvements in the 2.7 mg vorolanib insert group exceeded those in the aflibercept control arm (mean BCVA change +2.2 letters, mean CST change -38.8 microns). In addition, a subgroup analysis of eyes that were supplement-free at week 24 showed that compared to the aflibercept control arm, the DURAVYU 2.7 mg group had greater mean improvements from baseline in BCVA (+10.3 vs +3.0 letters) and CST (−117.4 vs -43.7 μm) as well as a higher percentage of eyes with no DME (43 percent vs 0 percent).

Consistent with findings from previous clinical trials conducted in eyes with wet age-related macular degeneration and nonproliferative diabetic retinopathy, the DURAVYU intravitreal insert demonstrated favorable safety. There were no ocular or systemic serious adverse events considered related to vorolanib intravitreal insert nor any cases of endophthalmitis, retinal vasculitis, intraocular inflammation, or insert migration into the anterior chamber.