Dry eyedisease compounds…
163
ISV-‐101
ISV-‐101 is a new drug of the company InSite Vision incorporating a low
dose of the non-‐steroidal anti-‐inflammatory (NSAID) bromfenac (Figure 12) and a
flow-‐able mucoadhesive polymer of
DuraSite
technology (75). This combination
enablesa slowreleaseof bromfenacover a longerperiodof time. Consequently the
eye aqueous humor is absorbing and retains a higher dose of bromfenac. The
extensionof thedurationof drug residenceon the surfaceof theeyeenablesbetter
penetration, improving efficacy, safety and dosing. Initial data from previous
clinical studies evaluating this combination demonstrated a favorable safety
profile. The company started Phase II clinical trials (ClinicalTrials.gov Identifier:
NCT01478555) in July2012on150patients toevaluate thesafety, tolerability, and
efficacy intopical administrationof differentdoseregimensof the ISV-‐101.
ESBA-‐105
ESBATechdeveloped ESBA-‐105 a single-‐chain antibody fragment that
targets tumornecrosis factor alpha (TNF-‐
α
) (76). Selective inhibitionof TNF-‐
α
has
the potential of modulating the inflammatory and immune response. Preclinical
studies demonstrated that topically administered ESBA105 attains therapeutic
levels in both the anterior and posterior segments of the eyewithout a need of a
penetration enhancer. Consequently, its drug penetration and ocular bio-‐
distribution appear highly attractive for clinical use to treat TNF-‐
α
connected eye
diseases (77). Alcon after the fusion with ESBATech conducted Phase II clinical
trials (ClinicalTrials.gov Identifier: NCT01338610) in April 2011 up to February
2012 to evaluate the efficacy of ESBA-‐105 10 mg/mL in 90 patients with severe
dry eye experiencing persistent ocular discomfort. The results demonstrated that
the compound topically applied penetrated into the anterior chamber of the
humaneyeat therapeutic levels (78).
DA-‐6034
Dong-‐APharmaceutical Co., Ltd is developing aMMP-‐9 inhibitor calledDA-‐
6034, consisting of 7-‐carboxymethyloxy-‐3’,4’,5-‐trimethoxy flavone monohydrate
(Figure 13) as possible treatment for dry eye. DA-‐6034 is a synthetic derivative of
eupatilin, a pharmacologically active flavone, capable to increase secretion of
mucin-‐like glycoprotein. It may increase as well the secretion of some mucin
species in conjunctiva and cornea. Mucin is a glycoprotein lubricating component
of tear film able to weaken moisture loss from tear evaporation. Choi and
