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.
■ FDA approved two ophthalmic drugs in 2012. Despite having set a seven-year record of 31 novel new drug approvals in 2012, the FDA approved only two new ophthalmic drugs last year. Zioptan (tafluprost), a once-daily topical glaucoma medication manufactured by Merck was approved in February, and Jetrea (ocriplasmin), a ThromboGenics drug for the treatment of symptomatic vitreomacular adhesion (VMA), received unanimous approval in October. Of the two new approvals, Jetrea is the more noteworthy as it marks the first medical therapy for VMA. Jetrea is administered as a single intravitreal injection.
■ Drs. Heier, Roth join Ohr scientific advisory board. Ohr Pharmaceutical, Inc., has added two prominent ophthalmologists to its Scientific Advisory Board comprised of leading retinal specialists to assist in advancing the Squalamine eye drop program through clinical efficacy trials. Ohr has recently initiated a 21-site phase 2 clinical trial using Squalamine eye drops to treat wet AMD.
Jeffrey S. Heier, MD, of Ophthalmic Consultants of Boston, and Daniel Roth, MD, of Retina Vitreous Center in New Jersey, will advise the company on its clinical programs and regulatory strategy, and provide strategic guidance to support the development of Squalamine in multiple neovascular ophthalmic clinical indications, including the initial target of wet AMD.
“Squalamine eyedrops have the potential to significantly advance the treatment of wet AMD, both from a patient’s convenience perspective as well as its unique mechanism of action, which may provide distinct or additional benefits from our current anti-VEGF agents,” said Dr. Heier.
■ Alimera seeks UK cost compromise on Iluvien. Alimera Sciences said the United Kingdom’s National Institute for Health and Clinical Excellence (NICE) has issued final draft guidance indicating that the company’s Iluvien implant is not recommended for the treatment of chronic DME considered insufficiently responsive to available therapies. While the Appraisal Committee acknowledged the clinical effectiveness of Iluvien in the treatment of vision impairment associated with chronic DME, it noted that cost-effectiveness thresholds for the product have not yet been met.
In response to the final draft guidance, Alimera is now developing a Patient Access Scheme (PAS) to address the Appraisal Committee’s cost concerns that pose a barrier to access for people in the United Kingdom with chronic DME who might benefit from Iluvien. The goal of the PAS will be to determine the appropriate pricing for Iluvien to ensure that treatment decisions are based on patient need rather than cost.
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.
■ Eylea developer voted top biotech company. Regeneron Pharmaceuticals, developer of the drug Eylea (aflibercept) for wet AMD and other retinal disease, was named “Biotechnology Company of the Year” for its achievements by Scrip Intelligence at the eighth annual Scrip Awards.
In presenting the award, Scrip said, “Regeneron has been transformed over the past year by the US approval of its first major product (Eylea). On the back of its highly successful launch, the company expects to become profitable for the first time in 2012.”
Leonard S. Schleifer, MD, PhD, president and CEO of Regeneron, said, “We are honored to be recognized by Scrip, a leading industry publication. This has indeed been a transforming time for Regeneron, as we went from having one approved drug to three, advanced investigational drugs into phase 3 trials, and created shareholder value that moved Regeneron into the top ranks of the biotechnology industry.” A 16-member panel of pharmaceutical industry executives, consultants and researchers voted on the award.
■ Iridex receives multi-spot scanning approval. Iridex Corp. announced FDA 510(k) and CE clearance of the TxCell Scanning Laser Delivery System. The new product is designed to save time when used in a variety of laser photocoagulation procedures by allowing physicians to deliver the laser in a multi-spot scanning mode, a more efficient method than the traditional single spot mode.
The TxCell Scanning Laser Delivery System combined with an Iridex IQ532 or IQ577 laser enabled with MicroPulse is designed to provide the ophthalmologist a highly versatile system with three laser modalities: multispot scanning, single spot standard and MicroPulse laser therapy. Initial shipments have commenced.
■ New Ozurdex needle. The FDA recently approved a new needle for use in the Ozurdex applicator. Allergan had received feedback from retina specialists about the glide factor and penetration of the old needle, which prompted the change.
The new needle is still 22-gauge, but from a different manufacturer with a different coating. There are no changes to the Ozurdex implant itself.
■ Aspirin use associated with AMD. A large-scale trial involving 4,691 participants as part of the European Eye Study found an association between frequent aspirin use and the incidence of AMD. The strongest associations linked daily aspirin use to early AMD and late, wet AMD. Overall, 17.3 % of all the study participants reported they used aspirin daily. The study was reported in a recent issue of the journal Ophthalmology. RP