Amakem starts phase 2 ROCK inhibitor study

A highly potent locally acting Rho Kinase (ROCK) inhibitor designed to reduce intraocular pressure (IOP) by acting specifically on the main outflow system in the eye is now in a phase 2 dose-ranging study, developer Amakem Therapeutics (Diepenbeek, Belgium) said in a news release.

The study is a multicenter, randomized, double-masked, placebo-controlled study with an optimized formulation of AMA0076 applied topically as eye drops. The study aims to enroll approximately 80 patients in the United States, Amakem said. The primary efficacy endpoint will be change in IOP from baseline at the end of 28 days of treatment. Secondary endpoints include IOP assessment at other time points as well as safety and tolerability assessments. The company expects to report top line results during the fourth quarter.

AMA0076 has previously demonstrated IOP reduction without significant hyperemia in a first-in-human study in patients with glaucoma and ocular hypertension, and an optimized formulation with significantly improved corneal absorption led to substantial IOP reduction with no significant hyperemia in a subsequent phase 1b study, Amakem said.

Squalamine being investigated as
DME treatment

A phase 2 investigator-sponsored trial is evaluating squalamine topical drops in patients with diabetic macular edema (DME), developer Ohr Pharmaceutical (New York) said in a news release.

Principal investigator Daniel Roth, MD, Retina Vitreous Center/NJ Retina, New Brunswick, N.J., said primary endpoints will measure change in retinal thickness and change in best corrected visual acuity (BCVA) over 24 weeks. The trial is designed to enroll up to 30 subjects at 3 sites in the United States. Patients will be randomized to receive a single injection of ranibizumab at baseline followed by treatment with either squalamine lactate ophthalmic solution 0.2% or placebo ophthalmic solution, administered QID for 24 weeks. 

Recombinant human nerve growth factor (rhNGF) was well tolerated in a phase 1 study for the treatment of neurotrophic keratitis, developer Dompé (Milan, Italy) said in a news release.

The study examined 18 patients (7 men and 11 women) suffering from moderate or severe neurotrophic keratitis resulting from diabetes, eye infections caused by the herpes virus, neurosurgical interventions and other related diseases. The patients enrolled in the study, who did not respond to currently available medical treatments, were divided into four groups. In the first group, patients were administered an eye drop solution for topical use at a dose of 10 µg/ml. In the second group, a simple vehicle was administered. In the third group, a dose of 20 µg/ml was given and, in the fourth group, a placebo was administered. At the end of the treatment, 11 patients had a notable improvement in corneal conditions.

Complete resolution of corneal lesions was recorded in the majority of patients, with similar percentages in the two groups treated with rhNGF at different doses, as well as an increase in corneal sensitivity in approximately one in every three patients.

rhNGF is now in phase 2 development and patient enrollment is underway. The study is being carried out at 39 centers in 9 countries across Europe. 

Merck (Whitehouse Station, N.J.) has sold its entire ophthalmic line to Santen (Osaka, Japan) for about $600 million, the two companies announced separately. Under terms of the agreement, Santen will receive all rights to Cosopt (dorzolamide hydrochloride/timolol maleate ophthalmic solution), Cosopt PS (dorzolamide hydrochloride/timolol maleate ophthalmic solution) 2%/0.5%, Trusopt (dorzolamide hydrochloride ophthalmic solution) sterile ophthalmic solution 2%, Trusopt PF (dorzolamide hydrochloride ophthalmic solution) preservative-free, Timoptic (timolol maleate ophthalmic solution), Timoptic PF (timolol maleate preservative-free ophthalmic solution in unit dose dispenser), Timoptic XE (timolol maleate ophthalmic gel forming solution), Saflutan (tafluprost), and Taptiqom (tafluprost/timolol maleate ophthalmic solution, in development) in Japan and key markets in Europe and Asia-Pacific.

Merck divested its U.S. ophthalmology business to Akorn Pharmaceuticals in 2013 and 2014. Merck will continue to sell its ophthalmology products in Latin America, Canada, Australia, the Middle East, Africa and other markets. 

RESEARCH BRIEFS

• In spite of the increasing cataract surgical rates and the more than adequate number of ophthalmologists in Latin America, it is not known how many ophthalmologists actually perform surgery, according to Juan Francisco Batlle and colleagues. In their longitudinal review study, they reviewed cataract surgical rates and other related indicators that have been reported to the VISION 2020 Latin America program since 2005. The weighted mean regional cataract surgical rate has increased by an impressive 70% since 2005, from 1,562 to 2,672 cataract surgeries per 1 million inhabitants. The weighted mean number of ophthalmologists per 1 million inhabitants in the region is approximately 62. Cataract surgical coverage varies widely in Latin America from a meager 15% in El Salvador to a more satisfactory 77% in Uruguay. Five recent surveys indicate that lack of awareness of cataract and the surgical treatment option and the cost of surgery are the main cataract surgical barriers. The authors concluded more comprehensive eyecare programs and training centers are needed that focus on reaching the underserved and unaware communities, increasing surgical output and uptake, and improving outcomes. The study is published online ahead of print in American Journal of Ophthalmology.
• One year postoperatively, the outcomes were similar with intraoperative intracameral triamcinolone injection and postoperative oral prednisolone for modulating inflammation after congenital cataract surgery, according to M.C. Ventura and colleagues. In their trial, children under 2 years of age were randomized to intraoperative intracameral injection of 1.2 mg/0.03 mL of triamcinolone acetonide (n=31 eyes) or 1 mg/kg per day of prednisolone syrup for 15 days postoperatively, which was then tapered over the following 2 weeks (n=29 eyes). In both groups, the mean intraocular pressure and central corneal thickness did not change significantly postoperatively (study group P=.922 and P=.149, respectively; control group P=.483 and P=.416, respectively). The groups had similar incidences of cell deposits (P=.517) and posterior synechiae (P=.247). No eye developed visual axis obscuration or had additional surgical procedures. All eyes had a clinically centered IOL. The study is published in Journal of Cataract & Refractive Surgery.
• CyPass Micro-Stent implantation (Transcend Medical, Menlo Park, Calif.), in combination with cataract surgery, was associated with minimal complications while substantially lowering intraocular pressure (IOP) and/or use of IOP-lowering medications, according to H. Höh and colleagues. In a multicenter, prospective, consecutive case series, 136 subjects (136 eyes) with OAG and requiring cataract surgery with 24-month postoperative data were included. A combined phacoemulsification procedure, with intraocular lens insertion and CyPass Micro-Stent implantation into the supraciliary space of the study eye, was performed. At baseline, all subjects were on glaucoma medication with either uncontrolled intraocular pressure (IOP; ≥21 mmHg, Cohort 1) or controlled IOP (<21 mmHg, Cohort 2). The most common adverse events were transient hypotony (15.4%) and micro-stent obstruction (8.8%), typically due to iris tissue overgrowth. Fifteen subjects (11%) required secondary incisional glaucoma surgery. For Cohort 1 (n=23), mean ± SD IOP was 15.8±3.8mmHg after 24 months (change, -37%±19%). Mean IOP decrease from baseline was statistically significant (P<0.0001) beginning at month 6. For Cohort 2 (n=59), mean ± SD IOP at 24 months was 16.1±3.2mmHg (change, 0%±28%). Mean decrease from baseline was statistically significant at months 6 (P=0.0188) and 12 (P=0.0356). Mean medication use decreased in both groups as well. The study is published in Klinische Monasblatter fur Augenheilkunde.

NEW PRODUCT BRIEFS

• Geuder (Heidelberg, Germany) has introduced the endoTRON532, a laser system for the posterior segment. The laser operates at 532 nm and provides a maximum output power of 1,500mW. The "excellent coagulation performance results in an extremely homogeneous, sharp-edged coagulation spot," the company said. The device is available as a standalone system or can be fully integrated into Geuder's megaTRON S4HPS.

Indications: The TECNIS® Toric 1-Piece posterior chamber lenses are indicated for the visual correction of aphakia and pre-existing corneal astigmatism of one diopter or greater in adult patients with or without presbyopia in whom a cataractous lens has been removed by phacoemulsification and who desire improved uncorrected distance vision, reduction in residual refractive cylinder, and increased spectacle independence for distance vision. The device is intended to be placed in the capsular bag.

Warnings: Physicians considering lens implantation should weigh the potential risk/benefit ratio for any circumstances described in the TECNIS® Toric 1-Piece IOL Directions for Use that could increase complications or impact patient outcomes. The clinical study did not show evidence of effectiveness for the treatment of preoperative corneal astigmatism of less than one diopter. The TECNIS® Toric 1-Piece IOL should not be placed in the ciliary sulcus. Rotation of the TECNIS® Toric 1-Piece IOL away from its intended axis can reduce its astigmatic correction. Misalignment greater than 30° may increase postoperative refractive cylinder.

Precautions: Accurate keratometry and biometry in addition to the use of the TECNIS Toric Calculator (www.TECNISToricCalc.com) are recommended to achieve optimal visual outcomes. The safety and effectiveness of the toric intraocular lens have not been substantiated in patients with certain preexisting ocular conditions and intraoperative complications. Refer to the TECNIS® Toric 1-Piece IOL Directions for Use for a complete description of the preexisting conditions and intraoperative complications. All preoperative surgical parameters are important when choosing a toric lens for implantation. Variability in any of the preoperative measurements can influence patient outcomes. All corneal incisions were placed temporally in the clinical study. Do not reuse, resterilize, or autoclave.

Adverse Events: The most frequently reported adverse event that occurred with the TECNIS® Toric 1-Piece IOL was surgical reintervention, which occurred at a rate of 3.4% (lens repositioning procedures and retinal repair procedures). Other reported events included macular edema, which occurred at a rate of 2.9% and retinal detachment which, occurred at a rate of 0.6%.

Caution: Federal law restricts this device to sale by or on the order of a physician.

Attention: Reference the Directions for Use labeling for a complete listing of Indications, Warnings and Precautions.

TECNIS is a trademark owned by or licensed to Abbott Laboratories, its subsidiaries or affiliates.

©2013 Abbott Medical Optics Inc.  www.AbbottMedicalOptics.com

2013.03.08-CT6527