EW Weekly, September 7, 2018

September 7, 2018
Volume 24 , Number 33

Phase 1 enrollment completed for KSI-301 for DME

Enrollment for a Phase 1 study of KSI-301 (Kodiak Sciences, Palo Alto, California) for diabetic macular edema has been completed. The open-label, single-ascending dose study has enrolled patients with diabetic macular edema to evaluate ocular and systemic safety and to establish a maximum tolerated dose of KSI-301, according to a company press release. "Dose escalation culminated in a maximal tested dose of 5.0 mg," the company reported. The press release noted that the agent has been safe and well tolerated in all subjects thus far, with no ocular inflammation or drug-related adverse events. KSI-301 is also targeted for investigation to treat wet age-related macular degeneration (AMD) and diabetic retinopathy.

IND application active for gene therapy ADVM-022

An Investigational New Drug (IND) application is now active for a planned multicenter, open-label, Phase 1, dose-escalation study of ADVM-022 (Adverum Biotechnologies, Menlo Park, California), a gene therapy candidate designed to treat wet AMD. ADVM-022 uses a proprietary vector capsid carrying an aflibercept coding sequence under the control of a proprietary expression cassette and is administered as a single intravitreal injection, according to a company press release. The OPTIC Phase 1 trial will assess the safety and tolerability of a single intravitreal injection of ADVM-022 in patients with wet AMD who are not responsive to anti-vascular endothelial growth factor treatment. The trial is slated to enroll 18 patients at six retinal centers across the U.S., with patients receiving a tapering prophylactic corticosteroid regimen. The trial's primary endpoint will be safety and tolerability of ADVM-022 at 24 weeks after a single intravitreal injection.

Results from Phase 3 trial of EGP-437 for noninfectious uveitis announced

Top-line results from a Phase 3 study for EGP-437 (EyeGate Pharmaceuticals, Waltham, Massachusetts) were announced this week. The agent is delivered through the EyeGate II Drug Delivery System in patients with non-infectious anterior segment uveitis. EGP-437 demonstrated clinical efficacy but did not demonstrate non-inferiority to the prednisolone acetate ophthalmic solution control group, as measured by the proportion of subjects with an anterior cell count of zero at day 14, according to the company. Leaders at EyeGate will continue to review data and assess strategic options for EGP-437.

Results reported from Phase 1/2 trial for QR-110 in Leber's congenital amaurosis 10

A Phase 1/2 trial for QR-110 (ProQR, Leiden, the Netherlands) found sustained improvement among subjects with Leber's congenital amaurosis 10 (LCA10), the company reported in a press release. The subjects have LCA10 due to the p.Cys998X mutation in the CEP290 gene. About 60% of the subjects had a clinically meaningful response in visual acuity and mobility course endpoints. There were no serious adverse events recorded. "Based on the emerging findings from the Phase 1 /2 trial, the company agreed with the [Food and Drug Administration] to submit a protocol to progress to a pivotal Phase 2/3 trial," according to the company press release. "In light thereof, the originally planned interim analysis at 6 months treatment was accelerated to the point when eight patients had reached 3 months of treatment." Because comparable activity was observed in the first two dose levels, the trial did not escalate up to the high dose, and trial enrollment stopped. The company will start a Phase 2/3 pivotal trial called ILLUMINATE in the first half of 2019.

ThromboGenics changes name to Oxurion

ThromboGenics (Leuven, Belgium), which develops treatments for retinal disorders, has changed its name to Oxurion NV. The name change was approved by stockholders.

Submit your ASCRS Film Festival entries today

Submissions are now being accepted for the 2019 ASCRS Film Festival. The deadline for submissions is Wednesday, October 17. Established in 1982, the Film Festival Awards honor the best filmmakers in ophthalmology. A grand prize winner, a runner-up, and a winner from each of the 10 categories will be announced during the 37th Annual Film Festival Awards at the 2019 ASCRS/ASOA Annual Meeting, May 3-7 in San Diego.

EyeWorld Reader Survey open until September 12

EyeWorld recently launched a survey to gather feedback from readers about our monthly news magazine. If you're a current or recent ASCRS member, please check your email inbox for a link to this important opportunity to share your thoughts about your EyeWorld reading experience. The survey will close September 12. Your opinion is important. Thank you for taking a few minutes of your time to provide us with your insights.

Research briefs

  • Outcomes were similar for endothelium-out and endothelium-in insertion methods for Descemet's membrane endothelial keratoplasty, according to results from a retrospective analysis led by Marianne Price, PhD. A total of 754 consecutive cases were included, all performed for Fuchs' dystrophy by two experienced surgeons. An IOL inserter was used by both surgeons. One surgeon always inserted the tissue scrolled endothelium outward (n=245), while the second surgeon tested three methods: endothelium-outward scroll configuration (n=161), endothelium-inward trifold configuration (n=172), and trifold configuration with concurrent use of an anterior chamber maintainer (n=176). Outcome measures were rebubbling rate, regrafting or failure within 6 months, and 6-month endothelial cell loss. Both the rebubbling rates and the 6-month graft failure/replacement rates were comparable across groups. The 6-month endothelial cell loss did not differ significantly. Tissue unfolding time was similar for both the scroll and trifold configurations. The study is published in Cornea.
  • A face-to-face upright seated position for patients who cannot lie flat during cataract surgery appears to be safe when performed by experienced surgeons, reported Tooba Sohail, MB BS. The researchers' prospective case series evaluated 240 cases at a university hospital in which patients sat upright or semi-recumbent and the surgeon sat or stood, facing the patient. For these cases, the microscope was rotated forward, and surgery was done via an incision in the lower corneal half using topical intracameral anesthesia. The common reasons for the need for face-to-face surgery were kyphosis, orthopnea, or both. Vitreous loss occurred in 5% of patients. All patients received a posterior chamber IOL, and no patient had a systemic adverse event. The findings are published in the Journal of Cataract & Refractive Surgery.
  • Oral vascular endothelial growth factors (VEGFs) used in more advanced cancer chemotherapy can have ocular side effects, reported Frederick T. Fraunfelder and Frederick W. Fraunfelder. The researchers reviewed spontaneous reports collected and evaluated by the National Registry of Drug-Induced Ocular Side Effects for pazopanib, sorafenib, and sunitinib. The most commonly reported side effects included blurred or decreased vision (389 cases), periocular or eyelid edema (273 cases), and superficial anterior segment toxicity (270 cases). Other side effects included ocular bleeding, retinal detachments or tears, and extraocular muscle disorders. Patients who are using oral VEGFs should be advised to seek ophthalmic consultation if retinal symptoms occur, the authors concluded. The study is published in the Journal of Ocular Pharmacology and Therapeutics.
  • An increased risk of Alzheimer's disease was found in patients with recent glaucoma diagnoses, established AMD diagnoses, and both recent and established diabetic retinopathy, reported Cecilia Lee and coresearchers. However, cataract was not associated with an increased risk of Alzheimer's disease development. Researchers used an adjusted hazard ratio for developing probable or possible Alzheimer's disease for recent (within 5 years) and established (longer than 5 years) diagnoses. The recent and established hazard ratios were 1.46 (P=.01) and 0.87 (P=.19) for glaucoma, 1.20 (P=.12) and 1.50 (P<.001) for AMD, and 1.50 (P=.045) and 1.50 (P=.03) for diabetic retinopathy. The research appears in Alzheimer's & Dementia.

This issue of EyeWorld Weekly Update was edited by Amy Goldenberg and Vanessa Caceres.

EyeWorld Weekly Update (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: 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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