EyeWorld Weekly Update, January 6, 2017

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January 6, 2017
Volume 21 , Number 49

ReSTOR +3.0 Multifocal Toric granted U.S. approval

The U.S. Food and Drug Administration (FDA) granted regulatory approval for the AcrySof IQ ReSTOR +3.0 D Multifocal Toric IOL, according to Alcon (Fort Worth, Texas). The new IOL is designed to address presbyopia and pre-existing corneal astigmatism at the time of cataract surgery in adult patients who desire good near, intermediate, and distance vision with an increased potential for spectacle independence. The product is already commercially available in the European Union, Australia, Canada, and many countries in Central and South America and Asia. Alcon plans to launch the lens during the first quarter.

Update on Rhopressa NDA filing

A contract manufacturer in Florida will not be ready for pre-approval inspection by the FDA until the end of February 2017, delaying the New Drug Application (NDA) filing of Rhopressa (netarsudil 0.02%), said developer Aerie Pharmaceuticals (Irvine, California). Aerie withdrew its initial NDA for the glaucoma drug in October 2016 after the contract manufacturer notified Aerie it was not prepared for FDA inspection. Aerie now expects to resubmit the Rhopressa NDA filing near the end of the first quarter of 2017.

Seciera meets primary, secondary endpoints in Phase 3 DED study

Sun Pharma (Mumbai, India) said a confirmatory Phase 3 study for Seciera (cyclosporine A, 0.09%), a patented, novel, proprietary nanomicellar formulation for the treatment of dry eye disease, showed statistically significant improvement in the primary endpoint, Schirmer's score ( p<0.0001). In this 12-week, multicenter, randomized, double-masked, vehicle-controlled Phase 3 confirmatory study, 744 dry eye patients were treated either with Seciera or its vehicle. After 12 weeks of treatment Seciera showed statistically significant improvement in the primary endpoint compared to vehicle. The demonstration of efficacy by Seciera at 12 weeks is earlier than other drugs approved for dry eye in the same class, according to Sun Pharma. Additionally, several key secondary endpoints showed statistically significant improvements compared to vehicle, with some showing an even earlier onset of action. Adverse events reported in the trial were mild to moderate in nature and similar to other approved drugs in the category, the company added.

CyclASol has positive results in Phase 2 DED study

Novaliq (Heidelberg, Germany) reported positive Phase 2 results on CyclASol, a preservative-free cyclosporine A solution for the treatment of moderate to severe dry eye disease. In 207 patients, CyclASol showed a "consistent reduction in corneal fluorescein staining, the primary sign endpoint, with an early onset of action over the 4-month treatment period," the company said. This Phase 2 randomized, double-masked, vehicle-controlled, multicenter U.S. study consisted of four treatment groups, including two CyclASol groups (0.05% and 0.1%), an open-label active control, and a placebo (vehicle control) group. Both CyclASol groups showed a significant improvement in corneal staining compared to vehicle over the 4-month treatment period. In particular, the central area of the cornea seems to benefit most, which is an important aspect for the visual function in dry eye patients. All treatment groups demonstrated improvement in symptoms, with CyclASol showing improvements over vehicle in subgroups. Data further indicates an early onset of action by reduction in corneal and conjunctival staining in as little as 14 days. Both CyclASol concentrations showed excellent safety, tolerability and comfort profile with 98% of the enrolled patients completing the treatment period. No serious adverse events (SAEs) related to CyclASol were reported.

Trabodenoson fails first Phase 3 study

Top-line results of MATrX-1, the first pivotal Phase 3 trial of trabodenoson for the treatment of primary open-angle glaucoma (POAG) or ocular hypertension, did not achieve its primary endpoint of superiority in reduction of IOP compared with placebo at all 12 time points, said developer Inotek Pharmaceuticals (Lexington, Massachusetts). This failure was, in part, due to a placebo response that was 2-3 mm Hg greater than that observed in Phase 2, the company added. Trabodenoson is a first-in-class, highly selective adenosine mimetic targeting the A1 subreceptor. Trabodenoson lowers IOP by augmenting the eye's natural function of the trabecular meshwork, the primary outflow pathway for aqueous humor and a site of pathology in glaucoma. Company executives noted that MATrX-1 did achieve several clinically meaningful secondary endpoints: The 6% dose was significant versus placebo in the daily IOP change from diurnal baseline at all days tested. Additionally, an analysis of responders (subjects with IOP reduction of 5 mm Hg or greater from baseline) indicated a statistically higher proportion of responders in the 6% trabodenoson group than the placebo group at all visits. There were no significant safety or tolerability events reported. The safety profile of trabodenoson was comparable to placebo. Notably, there was minimal drug-related hyperemia. Only four subjects (2.2%) discontinued the trial due to a treatment-related adverse event. A Phase 2 study will have top-line results mid-year; Inotek is waiting for full results before determining trabodenoson's future.

Blepharitis drug moves forward with Phase 2 study design

Nicox (Sophia Antipolis, France) is finalizing the study design for its first-in-human Phase 2 clinical trial evaluating the efficacy and safety of NCX 4251 compared to vehicle in patients with acute exacerbation of blepharitis. NCX 4251 is a novel ophthalmic suspension of fluticasone propionate nanocrystals, Nicox said, applied via an applicator swab to the eyelid margin. The primary objective of the first-in-human study is to demonstrate a statistically significant and clinically relevant difference in the proportion of subjects with clinical cure (defined as the absence of lid margin redness, lid debris, and lid discomfort) obtained with each dose of NCX 4251 vs. vehicle. The company is also using this study to identify the recommended dose to be used in the Phase 3 study. Subject to regulatory approval, Nicox plans to start the Phase 2 trial during the fourth quarter of 2017 and expects the trial to take approximately 1 year to complete.

RESEARCH BRIEFS

  • Infants' eyes had a similar rate of refractive growth after unilateral cataract surgery whether or not an IOL was implanted, results of the Infant Aphakia Treatment Study (IATS) found. S.R. Lambert and colleagues randomized patients at 12 sites across the U.S. to unilateral cataract extraction with contact lens correction versus IOL implantation. Patients had their rate of refractive growth (RRG3) calculated based on the change in refraction from the 1-month postoperative examination. Longitudinal refractive data were studied for 108 of 114 patients enrolled in the IATS (contact lens group, n=54; IOL group, n=54). The mean RRG3 was similar in the contact lens group (-18.0±11.0 D) and the IOL group (-19.0±9.0 D) (P=.49). The RRG3 value was not correlated with age at cataract surgery, glaucoma status, or visual outcome in the IOL group. In the aphakia group, only visual outcome was correlated with refractive growth (P=.01). The study is published in the Journal of Cataract & Refractive Surgery.
  • Treatment with interleukin (IL)-1 inhibitors is effective in the management of Behçet's disease (BD)-related uveitis and provides a long-term control of ocular inflammation in refractory and long-lasting cases, according to C. Fabiani and colleagues. Their multicenter retrospective observational study included 19 consecutive BD patients (31 affected eyes) who received treatment with anti-IL-1 agents anakinra (ANA) and canakinumab (CAN). At 12 months, ocular inflammatory flares (OIF) significantly decreased from 200 episodes/100 patients/year to 48.87 episodes/100 patients/year (p<0.0001). The frequency of retinal vasculitis identified by FA significantly decreased between the baseline and 3- and 12-month follow-up visits (p<0.0001 and p=0.001, respectively). OIF rate was significantly higher in patients co-administered with disease modifying anti-rheumatic drugs (81.8 episodes/100 patients/year) than in patients undergoing IL-1 inhibitors as monotherapy (0 episodes/100 patients/year) (p=0.03). No differences were identified on the basis of corticosteroid use and between patients administered with IL-1 inhibitors as the first line biologic approach or second line. Steroid dosage was significantly decreased at the 12-month visit compared to baseline (p=0.02). The study is published in Clinical Rheumatology.
  • A European study on translaminar pressure difference (TLP) in Caucasian patients with normal tension glaucoma (NTG) did not confirm either a lower lumbar cerebrospinal fluid pressure (CSF-p) or increased TLP compared to previous retrospective and prospective studies. A. Pircher and colleagues retrospectively analyzed the medical records of patients with open-angle glaucoma (OAG) at a single Swiss hospital from 2005 to 2015. A total of 67 eyes of 38 patients (mean age 68.6±11.3 years, 21 women and 17 men) underwent lumbar puncture during computer-assisted cisternography. The mean lumbar opening CSF-p measured 11.6±3.7 mmHg. The mean IOP in the right eye measured 14.7±2.4 mm Hg, in the left eye 14.7±2.5 mm Hg. The calculated mean TLP was 3.0±4.2 mm Hg in the right and 3.3±4.3 mm Hg in the left eye. There was no significant correlation between TLP and the mean defect of visual fields in both eyes. The study is published in Acta Ophthalmologica.

EYEWORLD WEEK Online is edited by Stacy Majewicz and Michelle Dalton.

EyeWorld Week Online (ISSN 1089-0319), a digital publication of the American Society of Cataract and Refractive Surgery and the American Society of Ophthalmic Administrators, is published every Friday, distributed by email, and posted live on Friday.

Medical Editors: David F. Chang, MD, chief medical editor; Bonnie An Henderson, MD, cataract editor; Clara C. Chan, MD, cornea editor; Reay H. Brown, MD, glaucoma editor; Kerry D. Solomon, MD, refractive editor; and John A. Vukich, MD, international editor

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