Abstract
Purpose :
Current anti-VEGF therapies for wetAMD reduce leakage and exudation but do not appear to reverse CNV progression. This study examined the hypothesis that ICON-1, an anti-Tissue Factor (TF) immunoconjugate protein, binds to CNV overexpressing TF and via a new mechanism of action acts to reduce CNV activity alone or in combination with ranibizumab (RBZ).
Methods :
EMERGE was a randomized, double masked, active control study in the United States. A total of 88 patients with treatment naïve CNV secondary to AMD were enrolled. Patients were randomized 1:1:1 and received intravitreal injections of ICON-1 0.3mg as monotherapy (n=30), ICON-1 0.3mg in combination with ranibizumab 0.5mg (n=30) or ranibizumab 0.5mg monotherapy (n=28). Patients received 3 initial monthly injections, then remained masked in their respective randomized group for additional 3 possible injections based on protocol retreatment criteria. Safety, BCVA letter score and CNV lesion activity were assessed monthly with optical coherence tomography (sdOCT) and quarterly with fluorescein angiography (FA).
Results :
No serious ocular adverse events were reported. The most frequently reported study eye ocular adverse events (AEs) in all groups were conjunctival hemorrhage (13.3-26.7%), vitreous floaters (10.7-13.3%), eye pain (3.3-23.3%) and retinal hemorrhage due to AMD (0-26.7%). After the 3 fixed injections, mean BCVA increased from baseline to Month 3 (primary endpoint) by 0.3 letters with ICON-1 monotherapy, 6.8 letters with ICON-1 in combination with RBZ, and 7.6 letters with RBZ monotherapy and was associated with CRT reduction in all treatment groups. From Month 3 to 6, fewer patients in the ICON-1 combination group (60%) received at least one additional injection compared to ICON-1 (82.8%) and RBZ (85.2%) monotherapy. Mean BCVA and mean CRT between months 3 and 6 were maintained in all treatment groups.
Conclusions :
Repeated intravitreal ICON-1 0.3mg injections alone or in combination with RBZ were well tolerated. BCVA gain was comparable in the ICON-1 combination and RBZ groups, although it was maintained with fewer treatments from Month 3 to 6 with ICON-1 combination. Together with signs of reduction in CNV activity (FA and sdOCT), these results provide biological signals of ICON-1 activity on the reduction of CNV progression.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.