SUBSPECIALTY NEWS

Drug Delivery Into the Suprachoroidal Space

Clearside encouraged by initial results.

■ Clearside Biomedical, Inc., a privately held developmental-stage ophthalmic company, said it has successfully dosed an initial group of patients in a safety and tolerability study using its proprietary ocular microinjection platform to deliver therapeutics to the retina via the suprachoroidal space (SCS).

The open-label study involved the administration of bevacizumab into the SCS of four wet AMD patients in a Mexico City clinic using Clearside’s microinjection platform. Administration to the SCS was achieved in all patients and was confirmed via ophthalmoscope.

“In my opinion, this study is pivotal for the company since it demonstrated that the suprachoroidal microinjection procedure was well-tolerated by the patient,” said Peter K. Kaiser, MD, professor of ophthalmology and retina specialist at the Cole Eye Institute at the Cleveland Clinic. “It was done only with topical anesthesia, making this a viable procedure to deliver medications to the retina and choroid.”

As demonstrated in a previous pre-clinical study, dosing into the SCS appears to be safe and well tolerated in the first month of safety assessments and is designed to be performed as an in-office procedure.

Clearside held a pre-Investigational New Drug (IND) meeting with the FDA to discuss the development plan of its initial product, CLS 1001. Based on this meeting, the company plans to file an IND application to enable initiation of the clinical program in the United States.

Europe Approves Eylea for Wet AMD

Bayer has the international rights.

■ Regeneron Pharmaceuticals said Eylea (aflibercept) injection has been approved by the European Commission for treatment of patients with wet AMD. According to the European Medicines Agency-approved Summary of Product Characteristics, Eylea treatment is initiated with one 2 mg injection per month for three consecutive months, followed by one injection every two months. There is no requirement for physician monitoring between injections. After the first 12 months of treatment, the reinjection interval may be extended based on visual and anatomic outcomes. In such cases, the treating physician determines the frequency of monitoring visits, which may be more often than the schedule of injections.

“We are pleased with the approval of Eylea in the EU,” said George D. Yancopoulos, MD, PhD, Regeneron’s chief scientific officer. “We, along with our partner, Bayer HealthCare, look forward to providing this new treatment option that will allow for every other month dosing, following three initial monthly injections, to wet AMD patients in the European Union.”

Eylea received US approval for treatment of wet AMD November 2011, and in Japan, Australia, Switzerland and other countries in 2012. Bayer HealthCare plans to launch Eylea in these countries in the near future. In the United States, Eylea was also approved for the treatment of macular edema following CRVO in September 2012. Shortly after receiving the European approval of Eylea for wet AMD, Bayer announced it had filed for European approval of Eylea for macular edema following CRVO, thus seeking to duplicate the two approved indications Eylea has already received in the United States.

“The Eylea launch continues to progress well and is driving strong sales and earnings growth. We now forecast 2012 US Eylea net product sales of $790 to $815 million,” said Leonard S. Schleifer, MD, PhD, president and CEO of Regeneron when he announced Regeneron’s third-quarter earnings. “With the recent approval of Eylea in the United States for the treatment of macular edema following CRVO and the anticipated launch beginning in Japan, Australia, and Europe, we expect Eylea to continue to drive growth through 2013 and beyond.”

Carotenoids May Reverse Early AMD

Small trial shows restoration of some visual function.

■ Supplements have primarily been recommended as a preventive measure for those who may be at risk for macular degeneration. However, researchers in Peking reported in a recent issue of Ophthalmology that lutein and zeaxanthin demonstrated the ability to restore some lost visual function in patients diagnosed with early-stage AMD.

In a randomized, double-masked, placebo-controlled trial, 108 patients ages 50 to 79 were randomly assigned to receive various amounts of lutein, lutein plus zeaxanthin, or placebo for 48 weeks. Macular pigment optical density and visual function were evaluated at baseline, 24 weeks and 48 weeks.

Among patients with early AMD, the researchers found that supplementation with lutein and zeaxanthin improved macular pigment, which played a causative role in boosting visual function. The researchers concluded that these supplements might be more than preventive and could be a factor in stopping the progression of early-stage AMD. They suggested more studies are needed to evaluate the effect of these carotenoids on the incidence of late AMD.

Changes in Genes a Cause of AMD

Smoking and diet seen as factors.

BY Bill Kekevian, Associate Editor

■ Genetic changes within the immune system may be linked to AMD development, according to a National Institutes of Health study. “This is the first epigenetic study revealing the molecular mechanisms for any eye disease,” said Robert Nussenblatt, MD, of the National Eye Institute (NEI).

Changes in the function of genes in the immune system can promote inflammation in the retina and lead to AMD, according to the study. These changes, the study has shown, come about via environmental factors, such as smoking and diet. These factors led to decreased levels of DNA methylation on the interleukin-17 receptor C gene (IL17RC). Without the DNA methylation, IL17RC protein levels increased.

Increased IL17RC proteins were found circulating in the blood and retinas of patients with AMD, but not in the control patients. The study “suggests IL17- and IL17RC-mediated immune responses can be crucial in causing AMD,” according the Lai Wei, MD, PhD.

Measuring gene activity offers the potential to identify at-risk patients early in the disease course, Dr. Wei said. In this study, investigators examined three pairs of twins (one pair identical and two pairs fraternal) where only one of the siblings had AMD. When compared with the unaffected twins, methylation patterns were altered in 231 genes of affected twins, a finding the NEI says is consistent with the hypothesis that environmental factors play a role in AMD development.