BasilioColligris, Jesús Pintor
166
cells isolated fromR932348-‐treatedmicealso showed reducedphosphorylationof
Stat5 after stimulationwith IL-‐2 (89). The company in July 2013, started Phase II
safety, tolerability and pharmacokinetics studies (ClinicalTrials.gov Identifier:
NCT01900249) for 0.2%and 0.5%R932348 ophthalmic solution in patientswith
dryeyedisease.
EBI-‐005
ElevenBiotherapeutics is developing chimeric IL-‐1 receptor type I agonists
and antagonists as dry eye treatment. These non-‐naturally occurring cytokine
domains canmodulate cellular signaling response to interleukin-‐1 receptor I (IL-‐1
RI), and to detect and or even bind on cellular receptors(90). The drug started in
December 2012 Phase I multi-‐center clinical trials (ClinicalTrials.gov Identifier:
NCT01745887)with the name EBI-‐005-‐2, an IL-‐1 receptor blocker, single-‐domain
protein, optimized for topical ocular delivery. The EBI-‐005 has been validated in
clinical proof-‐of-‐concept studies inwhich IL-‐1 blockagewas shown to be safe and
well toleratedwithout adverse side effects. According to the results presented in
ARVO 2012 (91) it was created by combining the IL-‐1 receptor binding the sub-‐
domains IL-‐1β and IL-‐1Ra. During the pre-‐clinical trials EBI-‐005was shownmore
active than topical Cyclosporine (the active ingredient of
Restasis
™ ophthalmic
emulsion eye drops) inmousemodels. Topical delivery resulted in distribution to
multiple eye compartments, but very lowsystemic exposure in rabbits (F<0.2%).
EBI-‐005 was 9°C more thermally stable than anakinra an interleukin-‐1 receptor
antagonist (92). Eleven Biotherapeutics presented promising preliminary clinical
data fromthe trials.
CONCLUDINGREMARKS
Many of the above mentioned potential drugs are anti-‐inflammatory
compounds and some are mucin secretagogue, promoting mucin and water
production, and also there are a few eye lubricants. Most of the anti-‐
inflammatories are corticosteroids because of their noteworthy anti-‐inflammatory
properties and rapid action. Normally they are used for a limited period of time
and depending on the severity of the case, after treatment the patient returns to
the initial inflammatory condition. This limitation makes them unsuitable for
chronic dry eye therapy as steroidal compounds present important side effects,
such as increase in intraocular pressure and posterior sub-‐capsular cataract (93).
