EW Weekly, November 1, 2019

Secondary analyses announced from Phase 2 trial for NCX 470 for glaucoma
Secondary analyses from the Dolomites Phase 2 trial with NCX 470 were announced by Nicox. NCX 470 is designed to reduce IOP in patients with open-angle glaucoma or ocular hypertension. Earlier, Nicox announced that in the Dolomites trial, NCX 470 met its primary endpoint of noninferiority and showed statistical superiority to latanoprost. In the secondary analysis, researchers found that all doses of NCX 470 (0.021%, 0.042%, and 0.065%) met the prespecified primary efficacy endpoint of noninferiority to latanoprost for reduction from baseline in mean diurnal IOP at day 28. IOP was lowered with each concentration of NCX 470 that was tested. The most frequent adverse event was conjunctival hyperemia in 16.7% of NCX 470 0.065% patients compared with 6.5% of latanoprost patients. No serious adverse events or treatment-related systemic effects occurred. According to the company press release, Nicox leaders will propose to the FDA NCX 470 0.065%—the highest concentration used in the Dolomites trial—and a 0.1% concentration.

Primary endpoint met in Phase 2b trial of Zimura for geographic atrophy
In a Phase 2b randomized, controlled trial, Zimura (avacincaptad pegol, Iveric bio) met its prespecified primary endpoint of lowering the rate of geographic atrophy growth in patients with dry AMD, according to a company press release. The reduction in the average rate of geographic atrophy growth over 12 months was 27.38% for the Zimura 2 mg group, compared with the corresponding sham control group, and 27.81% for the Zimura 4 mg group, compared with the corresponding sham control group. Both differences were statistically significant. Data from patients receiving Zimura 1 mg were not part of the prespecified statistical analysis, but researchers found that, on average, the percent geographic atrophy growth from baseline to month 12 in that group was less than for the corresponding sham control group. The most frequently reported adverse ocular event was related to the injection procedure. Zimura is the company's complement factor C5 inhibitor.

First patient dosed in third cohort of OPTIC trial for ADVM-022 gene therapy for wet AMD
The first patient has been dosed in the third cohort of nine patients in the ongoing OPTIC Phase 1 clinical trial for ADVM-022 (Adverum Biotechnologies) to treat wet AMD. Patients in this third cohort receive a single intravitreal injection of the gene therapy candidate ADVM-022 at a dose of 2 x 10^11 vg/eye, according to a company press release. The OPTIC Phase 1 trial is a multicenter, open-label trial to assess the safety and tolerability of a single intravitreal injection of ADVM-022 in patients with wet AMD who are responsive to anti-vascular endothelial growth factor treatment. There were six patients in the trial’s first cohort and six patients in the second cohort. There also will be a fourth cohort. ADVM-22 uses the vector capsid AAV.7m8, carrying an aflibercept coding sequence under the control of a proprietary expression cassette, according to the company. The FDA gave ADVM-022 Fast Track designation.

Rare Pediatric Disease designation given to sepofarsen for LCA10
The FDA has given a Rare Pediatric Disease designation to sepofarsen (ProQR) for the treatment of Leber's congenital amaurosis 10, the company announced. Sepofarsen is a first-in-class, investigational, RNA-based oligonucleotide designed to address the underlying cause of Leber's congenital amaurosis 10 due to the p.Cys998X mutation in the CEP290 gene.

Clinical program for MicroLine for presbyopia accelerated
Eyenovia announced acceleration of its MicroLine program toward Phase 3 development. The microdose therapeutics using patented piezo-print delivery technology under the MicroLine program are designed to improve near vision in patients with presbyopia. The company expects to initiate and complete its Phase 3 VISION trials for MicroLine in 2020, according to a company press release.

Submit your nomination for the inaugural ASCRS Educator Award
The new ASCRS Educator Award recognizes an ASCRS member who has made education an enduring career priority. Nominees must: have demonstrated passion and commitment to education, leadership, and selflessness in the pursuit of expanding knowledge in the interest of improving patient outcomes; be an ophthalmologist focused on anterior segment surgery; have at least 5 years in practice; and be a current ASCRS member. Nominations are due by November 29. Find more information at ascrs.org/educatoraward.

Research briefs
  • In a prospective, randomized, comparative study, SMILE offered more safety and objective visual acuity compared with LASIK, reported Xiaonan Yang, PhD, and coresearchers. SMILE also had comparable stability and efficacy and slightly inferior predictability. All 60 patients had a maximum myopic meridian exceeding 10 D. Thirty eyes were corrected with SMILE, and 30 were corrected with femtosecond LASIK. All patients received preop and 6-month postop exams. At 6 months, the uncorrected visual acuity was –0.01 and –0.05 in the SMILE and LASIK eyes, respectively (P = 0.080). Corrected visual acuity was –0.07 and –0.08, respectively (P = 0.624). Postop sphere equivalent was –0.20 and –0.03, respectively. The measured corneal thickness was lowered by 137.40 µm and 155.06 µm, respectively. Changes in higher-order aberrations and spherical aberration were slightly smaller with SMILE compared with LASIK. The study is published in the Journal of Cataract & Refractive Surgery.
  • A randomized clinical trial was not able to show that goniosynechialysis with phaco had additional IOP lowering after 1 year compared with the use of phaco alone, according to Rahat Husain, MD(Res), and coresearchers. All patients had synechial primary angle-closure disease and cataract. The 78 patients were randomized to have phaco with IOL implantation alone or phaco, IOL implantation, and goniosynechialysis. The main outcome was successful control of IOP at 12 months, defined as an IOP of 21 mm Hg or lower without the use of topical IOP-lowering medications and a lowering of the IOP by 20% or more from baseline IOP. The mean IOP baseline in the phaco-alone group was 22.3 mm Hg and 22.9 mm Hg for the phaco/goniosynechialysis group. At 1 year, the mean IOP was 14.3 mm Hg for the phaco-alone group and 15.9 mm Hg for the phaco/goniosynechialysis group. Successful control at 1 year took place in 52.5% of patients in the phaco-alone group and 57.9% in the phaco/goniosynechialysis group. Medication use decreased from a mean of 2.2 at baseline to 0.5 in the phaco-alone group and 1.9 to 0.6 in the phaco/goniosynechialysis group. Postop complications were similar in both groups and included IOP spike, excessive anterior chamber inflammation, and posterior capsule opacification. The research appears in JAMA Ophthalmology.
  • Clinicians should limit their reliance on eyelid margin vascularization as a diagnostic criterion for meibomian gland dysfunction (MGD), Max Blumberg, MD, and coresearchers concluded, based on results from their cross-sectional study. Consecutive cornea clinic patients were enrolled, and eyelid margin vascularization was graded qualitatively from slit lamp photos. Skin pigmentation was quantified from digital photos. MGD was designed as an abnormal quantity or quality of meibum or increased pressure required to express meibum. Additional tests performed included infrared meibography, Schirmer’s testing, and a dry eye questionnaire. Among the 47 participants, eyelid margin vascularization was less common in subjects with dark compared to light pigmentation, although the prevalence of MGD as seen via clinical evaluation did not vary significantly between the groups. Use of eyelid margin vascularization alone was not sensitive for MGD diagnosis. Sensitivity was 17% when limited to those with dark pigmentation. The study appears in Clinical Ophthalmology.

This issue of EyeWorld Weekly was edited by Stacy Jablonski and Vanessa Caceres.

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

Medical Editors: Eric Donnenfeld, MD, Chief Medical Editor; Rosa Braga-Mele, MD, Cataract Editor; Clara Chan, MD, Cornea Editor; Nathan Radcliffe, MD, Glaucoma Editor; and Vance Thompson, MD, Refractive Editor

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