Eleven Biotherapeutics Inc.'s lead candidate EBI-005 failed to outperform a vehicle control in a phase III study of moderate to severe dry eye disease, driving company shares (NASDAQ:EBIO) down 69.2 percent to $3.69 on Monday. The drug missed both of the study's co-primary endpoints, leading Eleven to call off an additional planned phase III study to concentrate instead on an area where it still sees potential for the drug in allergic conjunctivitis.
The interleukin-1 receptor blocker failed to beat the vehicle on either total corneal fluorescein staining score, a sign of dry eye disease, and patient-reported measurement related to ocular pain and discomfort. Eleven compared the mean change from baseline at week 12 for treatment with EBI-005 to treatment with vehicle control. Patients with dry eye disease in both the EBI-005 and vehicle treatment groups showed statistically significant improvement from baseline on the co-primary endpoints, but there was no statistically significant difference between the EBI-005 treated group and the control group on the co-primary endpoints or any secondary endpoints.
The Cambridge, Mass.-based company enrolled 669 subjects in the U.S.-based study, randomizing them 1:1 to either EBI-005 or vehicle eye drops.
News of the phase III miss arrived less that two weeks after Eleven reported that the topical drug "demonstrated a clinically relevant effect in dry eye disease" ahead of the Association for Research in Vision and Ophthalmology 2015 Annual Meeting, an outcome that Eleven Biotherapeutics president and CEO Abbie Celniker said the company saw no "immediate path forward" for the drug and would need to further assess the results from the OASIS study before determining the fate of its dry eye program, the most advanced in its pipeline and an asset for which the company holds all rights. "Our conclusions about EBI-005 based on this well-powered, well-executed study have us very confident that we would not be moving forward with our existing plans," Celniker added on a conference call discussing the data. "We moved as quickly as we could to get this data out to everybody, and as a result, there's still a bit more work for us to do to fully understand all the different aspects of the study, including study demographics, patient responses and some subset analyses that we'll be doing."
One bright spot in the phase III data, Eleven pointed out, was that EBI-005 appears to have a favorable tolerability profile. Fewer than 5 percent of patients reported eye irritation and there were no treatment-related serious adverse events. With that encouragement, it's turning its attention to allergic conjunctivitis, a disease in which it reported positive phase II data in October 2014. In that study, EBI-005 demonstrated statistically significant improvements in ocular itching, tearing and nasal symptoms in the late phase allergy response in moderate to severe allergic conjunctivitis patients challenged with allergen, using the conjunctival allergen provocation model.
The company assured investors that despite the late-stage setback in dry eye, it still has enough cash and cash equivalents to move EBI-005 into a pivotal study for allergic conjunctivitis in the second half of the year, estimated to cost around $6 million. The company said it will also be able to keep advancing its interleukin-6 ligand inhibitor EBI-031, for diabetic macular edema. Pharmacokinetic studies for EBI-031, which has been optimized for intravitreal administration using Eleven's AMP-Rx technology, confirmed the ability of EBI-031 to inhibit interleukin-1 signaling and extend vitreal retention compared to existing therapies. The company plans to file an investigational new drug application with the FDA by the end of this year.
Eleven has about $59 million in cash and cash equivalents, which it expects will finance its current plans into the second half of 2016, it said. It's carrying about $15 million in debt.