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Karen Tubridy, Michael H Goldstein, Jennifer Agahigian, Marianne Magill, Joseph Kovalchin, Eric S Furfine, Abbie Celniker; Clinical Development of EBI-005, a Novel Interleukin-1 Receptor Inhibitor, for Patients with Ocular Surface Inflammation. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4488.
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Interleukin-1 (IL-1) is a key mediator of ocular surface inflammation in dry eye disease (DED) and allergic conjunctivitis (AC). IL-1 is important not only in the initiation and maintenance of the inflammatory response, but also in mediating hypersensitization of peripheral nerves. EBI-005 is an IL-1 receptor inhibitor specifically designed and engineered for topical ophthalmic delivery. EBI-005 has been evaluated in several randomized, controlled clinical trials in DED and AC.
In a phase 1 healthy volunteer study, 16 subjects were randomized to topical EBI-005 (two different doses) or vehicle control 3x/day for one day. In a double-masked, placebo-controlled phase 2 study, 74 subjects with moderate to severe DED were randomized to receive vehicle or EBI-005 (5 mg/mL or 20 mg/mL) 3x/day for six weeks. In an exploratory, phase 2 study, 159 subjects with moderate to severe AC were randomized to EBI-005 or vehicle control and assigned to one of two different models of AC. Most recently, in a double-masked, placebo-controlled phase 3 study in subjects with moderate to severe DED, 669 subjects were randomized to receive vehicle or EBI-005 5 mg/mL 3x/day for 12 weeks. Safety, biological activity and immunogenicity were assessed.
Topical EBI-005 was generally safe and well tolerated in all studies. No drug specific antibodies have been detected to date. There were no treatment related serious ocular or non-ocular adverse events. In the phase 2 DED study, EBI-005 significantly improved signs and symptoms of DED compared to baseline at week six by up to 30% (p<0.001) and 36% (p<0.001) respectively. In the phase 2 AC study, EBI-005 showed statistically significant (p<0.05), clinically meaningful (>25%) improvement in symptoms of AC including ocular itching, ocular tearing and total nasal symptoms at multiple time points compared to vehicle.
Topical EBI-005 treatment is a promising new therapy for patients with moderate to severe dry eye disease and late phase allergic conjunctivitis. These results further validate the importance of IL-1 blockade in DED and AC. They support continued development of topical EBI-005 in these indications to further characterize the safety and efficacy of the drug in patients with ocular surface inflammation.
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