BasilioColligris, Jesús Pintor
158
(ClinicalTrials.gov Identifier: NCT01250171). The study reports suggest that both
substances arewell tolerated inmost patients, andno serious adverse effects have
been reported. Thedrugs provide significant advantages over existing competitive
therapies, including bimonthly administration and an approved use in children
(40-‐42).
MIM-‐D3
Mimetogen Pharmaceuticals Inc. is developing MIM-‐D3, a small molecule
mimicking the nerve growth factor (NGF) activity (Figure 5). NGF stimulates the
conjunctival cell glycoconjugate secretion and during
in vivo
trials demonstrated
therapeutic efficacyondry eyedisease (43). NGFplays an important role inocular
surface maintenance, corneal wound healing, displaying a mucin secretagogue
activity in conjunctival cells (44). Jain and colleagues during evaluation studies
demonstrated that a 1% MIM-‐D3 dose increased glycoconjugate concentration,
improving the quality and stability of tear film and the healing on the ocular
surface in dry eye (45). Mimetogen conducted Phase II safety and efficacy studies
(ClinicalTrials.gov Identifier: NCT01257607) from December 2010 to October
2012, on 150 patientswith the application of 1%MIM-‐D3 and 5%MIM-‐D3 for 28
days. Unfortunately the target primary endpoints were not met completely.
Despite this negative development the company continues the development
consideringMIM-‐D3asapotent compound(46).
DIFLUPREDNATE
Alcon is evaluating the corticosteroid Difluprednate-‐Durezol, a butyrate
ester of 6(alpha),9(alpha)-‐difluoro prednisolone acetate as a potential treatment
for dry eye disease (Figure 6) (47). This corticosteroid is preventing the
phospholipid release and decreases the eosinophil action.
Durezol
received
approval from the FDA in 2008 as the first ophthalmic steroid for the
postoperative inflammation and pain. Alcon started clinical trials Phase II
(ClinicalTrials.gov Identifier:NCT01276223) in January2011 for theDifluprednate
ophthalmic emulsion 0.05%, one drop in each eye twice per day, on 726 patients,
as an anti-‐inflammatory treatment of dry eye disease. Mulki and colleagues are
suggesting that difluprednate 0.05% ophthalmic emulsion exhibits enhanced
penetration, decent bioavailability, rapid local metabolism and strong efficacy,
witha lowincidenceof adverseeffectsandacomparablesafetyprofile (48).
