Novel Therapy for Patients With Moderate to Severe Dry-Eye Disease: Topical IL-1 Receptor Blocker

Goldstein, Michael

Novel Therapy for Patients With Moderate to Severe Dry-Eye Disease: Topical IL-1 Receptor Blocker

Sunday, April 27, 2014: 1:43 PM

Room 150 (Boston Convention and Exhibition Center)

Michael H. Goldstein, MD, Tufts Medical Center, Boston, MA, USA

Jennifer L. Agahigian, Eleven Biotherapeutics, Cambridge, MA, USA

Gregory Zarbis-Papastoitsis, PhD, Eleven Biothereapeutics, Cambridge, MA, USA

Kathryn Golden Cambridge, MA, USA

Joseph T. Kovalchin, PhD, Eleven Biotherapeutics, Cambridge, MA, USA

Eric Furfine, PhD, Eleven Biotherapeutics, Cambridge, MA, USA

Narrative Responses:

Purpose
IL-1, a critical cytokine in initiating and maintaining the inflammatory response in multiple diseases including DED, also mediates nociception. EBI-005 was developed as an IL-1 blocker optimized for topical delivery. This presentation describes a multi-center, double-masked, vehicle controlled, environmental trial in patients with moderate to severe DED using topical EBI-005.

Methods
In a double-masked, placebo-controlled study, conducted at 8 sites in the United States, 74 subjects with moderate to severe DED were randomized to receive vehicle, EBI-005 5 mg/mL or EBI-005 20 mg/ml. Subjects were dosed 3x/day for six weeks with topical EBI-005 or vehicle control. Safety assessments included: adverse event reporting, complete ophthalmic examination, corneal esthesiometry, corneal pachymetry, ocular surface microbiology, and serum laboratory testing. Assessments of efficacy included: corneal fluorescein staining (CFS), OSDI, and rescue tear use.

Results
Topical EBI-005 was safe and well tolerated. No patients dropped out or had serious AEs. EBI-005 significantly reduced signs and symptoms of DED. Treated patients showed improvement from baseline (p < 0.001) of 33% in total cornea CFS, 36% for total OSDI score and 46% for eye pain. Subjects with baseline OSDI scores under 50 had particularly strong responses; a 39% improvement in total corneal CFS, 41% total OSDI score and 61% in eye pain. These effects were greater than for vehicle control subjects. Treated patients used significantly fewer rescue artificial tears than those receiving vehicle control (p < 0.029).

Conclusion
Topical EBI-005 treatment is a promising, novel, topical, biologic therapy for patients with DED. These results further validate the importance of IL-1 blockade in DED and support continued development of the drug in a larger study designed to further characterize the safety and efficacy of EBI-005 in patients with DED.