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Eye Drug Flunks Phase III Test
Disappointing results have been announced from a pivotal phase III study of EBI-005, an investigational drug candidate for patients with moderate-to-severe dry eye disease.
The double-masked, randomized, controlled Efficacy and Safety Study of EBI-005 5 mg/mL Topical Ophthalmic Solution Versus Vehicle Control in Subjects With Moderate to Severe Dry Eye Disease (OASIS) included 669 patients. The study’s co-primary endpoints were the total corneal fluorescein staining score and the patient-reported measurement related to ocular pain and discomfort based on the Ocular Surface Disease Index (OSDI). Both endpoints compared the mean change from baseline at week 12 for treatment with EBI-005 versus a vehicle control.
EBI-005 did not meet either of the two co-primary endpoints. Moreover, there were no statistically significant differences between the EBI-005–treated patients and those given a vehicle control on the study’s co-primary endpoints or on any secondary endpoints.
While the change from baseline on the co-primary endpoints was greater in the vehicle group than in the EBI-005 group, the differences between the two groups were not statistically significant, but the drug’s developer (Eleven Biotherapeutics) believes that the differences were not clinically meaningful.
EBI-005 was generally well tolerated, with fewer than 5% of patients reporting eye irritation and with no reports of treatment-related serious adverse events. Approximately 13% of the patients in the study reported using artificial tears, with no difference in artificial tear use between the EBI-005 group and the vehicle control group. Overall, 92% of the patients completed the study.
EBI-005 is a topically administered interleukin-1 (IL-1) receptor blocker in development as a protein therapeutic for inflammatory diseases at the surface of the eye. The EBI-005 development program is based on the role that elevated levels of the inflammatory cytokine IL-1 play in the initiation and maintenance of the inflammation, pain, redness, itching, and other symptoms associated with ocular-surface diseases.
Eleven Biotherapeutics announced that it intends to advance EBI-005 into late-stage clinical development for allergic conjunctivitis, with plans to initiate a pivotal phase III study in patients with moderate-to-severe disease in the second half of 2015. Allergic conjunctivitis is mechanistically different from dry eye disease. The ocular surface inflammation associated with allergic conjunctivitis is initiated by a single, central mechanism of allergen stimulation, whereas the underlying causes of ocular surface inflammation in “dry eye” disease are diverse.
In October 2014, Eleven Biotherapeutics reported the results from a phase II study of EBI-005 in patients with allergic conjunctivitis. This study demonstrated statistically significant improvements in ocular itching, tearing, and nasal symptoms in the late-phase allergy response in patients with moderate-to-severe allergic conjunctivitis challenged with allergen, using the conjunctival allergen provocation model.
Source: Eleven Biotherapeutics; May 19, 2015.