Eyeworld

JUNE 2019 | EYEWORLD | 43 R acid [DHLA]) once within the lens. DHLA reduces disulfide bonds between lens proteins and restores lens microfluidics. Proof of concept was confirmed in vitro with human cadaver lenses and in vivo in rabbit eyes, where in both trials the drug produced lens softening and an increase in lens deforma- bility, Dr. Korenfeld said. Clinical trial The Phase 1/2 clinical study evaluated safety and efficacy of EV06 ophthalmic solution 1.5% in improving distance corrected near visual acuity (DCNVA) in subjects with presbyopia. The prospective, randomized, double-masked, placebo-controlled study included 75 patients (45–55 years) with hyperopia, myopia, or em- metropia and a diagnosis of presbyopia from four U.S. sites. Patients were randomized 2:1 (EV06=50: placebo=25). The study drug was given for 91 days and patients were monitored during a 7-month follow-up period. At baseline, the study patients had DCN- VA below 20/40 in each eye, best corrected distance visual acuity (BCDVA) of 20/20 or better in each eye, and a difference of ≤0.50 D between manifest refraction spherical equivalent and cycloplegic refraction spherical equivalent. Visual acuity improvements were most pronounced when subjects employed bilateral vision, with 84% achieving 20/40 bilateral vi- sion or better versus 52% in the placebo group. Fifty-three percent of the study participants achieved a ≥0.2 logMAR change in the bilateral vision versus 22% in placebo. "EV06 was safe and well-tolerated," Dr. Korenfeld said. "No subjects discontinued, and there were no sight threatening AEs or changes in IOP. The drug was comfortable upon instal- lation and caused no change in best correct- ed distance visual acuity, manifest refraction spherical equivalent, cycloplegic refraction, or in pupil diameter." Persistent drug effect An observational follow-up assessment on the long-term effects of bilaterally dosed topical lipoic acid choline ester eye drops demonstrated EV06 (lipoic acid choline ester) is a prodrug. EV06 penetrates the cornea and is metabolized into choline and lipoic acid, two naturally occurring substances. Enzymes within lens fiber cells chemically reduce lipoic acid to active form dihydrolipoic acid (DHLA). DHLA reduces disulfide bonds between lens proteins and restores lens microfluidics. Source: Michael Korenfeld, MD some interesting results. The drug effects on near visual improvement persisted in the study group long after dosing with EV06 was stopped at day 91. Dr. Korenfeld reported significant effects compared to placebo 241 days after the end of the study period, with only a small amount of treatment degradation. "Seven months after the end of the 3-month study time, 39% of the subjects treat- ed maintained a ≥0.2 logMAR change in bilater- al near vision, compared to only 6% in placebo. More trials using EV06 are being planned for 2019," he said. According to Dr. Korenfeld, EV06 was first developed based on the hypothesis that the oxidation of lens proteins was at least partially responsible for lens stiffness in presbyopia and that it might be reversed chemically. "It made sense from a theoretical standpoint. Then it was demonstrated in vitro. Now the hypothesis is being supported by data collected in an active treatment setting, in terms of visual outcomes, significant safety issues, and adverse events. It is plausible that the effect of lipoic acid on 'softening' lens proteins could open up further treatment options with the drug. It is conceiv- able that the early, pre-cataract application of topical EV06 could potentially be used to delay or prevent nuclear sclerotic cataract," he said. Lipoic acid choline ester Choline Lipoic acid Dihydrolipoic acid

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