VEGF-Trap has Positive 1-Year Data
Wet AMD Drug Requires Fewer Injections.
■ Regeneron Pharmaceuticals and partner Bayer HealthCare AG reported that patients with wet AMD receiving VEGF Trap-Eye in a phase 2 extension study on an as needed dosing schedule continued to show highly significant improvements at 52 weeks in the primary and key secondary endpoints of retinal thickness and vision gain.
In this double-masked, prospective, randomized, multicenter trial, 157 patients were randomized to 5 dose groups and treated with VEGF Trap-Eye in 1 eye. Two of the groups initially received monthly doses of 0.5 mg or 2.0 mg of VEGF Trap-Eye at weeks 0, 4, 8, and 12 and 3 groups received quarterly doses of 0.5, 2.0, or 4.0 mg of VEGF Trap-Eye at baseline and week 12.
Following the initial 12-week fixed-dosing phase of the trial, patients continued to receive therapy at the same dose on a PRN dosing schedule based upon the physician assessment of the need for retreatment in accordance with pre-specified criteria. Patients were monitored for safety, retinal thickness, and visual acuity (VA). The new data represent the final 1-year analysis from the 52-week study.
Patients receiving 4 monthly doses of VEGF Trap-Eye, either 2.0 or 0.5 mg, for 12 weeks followed by PRN dosing thereafter achieved mean improvements in VA vs baseline of 9.0 letters and 5.4 letters, respectively, and mean decreases in retinal thickness vs baseline of 143 μm and 125 μm at week 52, respectively. During the 40-week PRN dosing phase, patients initially dosed on a 2.0 mg monthly schedule received, on average, only 1.6 additional injections and those initially dosed on a 0.5 mg monthly schedule received, on average, 2.5 injections. Genentech's Lucentis, the leading drug for treating wet AMD, usually requires maintenance injections every 6 to 8 weeks.
For all dose cohorts combined, there was a 5.3 mean letter gain in VA vs baseline at the week 52 evaluation visit. The mean decrease in retinal thickness for all dose groups combined at week 52 was 130 μm vs baseline. During the week 12-to-week-52 PRN dosing period, patients from all dose groups combined received, on average, 2 additional injections.
VEGF Trap-Eye was generally well tolerated and there were no drug-related serious adverse events. There was 1 reported case of culture-negative endophthalmitis/uveitis in the study eye and 1 arterial thrombotic event, neither of which was deemed to be drug-related. The most common adverse events were those typically associated with intravitreal injections.
"Based upon retinal physicians' feedback, there remains a significant unmet medical need for a treatment for wet AMD that can reliably improve visual acuity over time without the need for monthly intravitreal injections," said George D. Yancopoulos, MD, PhD, president of Regeneron Research Laboratories. "We are excited about these study findings and the potential for VEGF Trap-Eye to fulfill this need pending the results of our ongoing phase 3 clinical studies."
EyeGate Begins Drug-Delivery Study
Electronic Stimulation Infuses Medicine.
■ EyeGate Pharma has initiated a phase 2 proof-of-concept study for drug delivery through a noninvasive process known as iontopheresis. The study will enroll up to 40 patients with noninfectious acute anterior-segment uveitis.
The principal investigator is C. Stephen Foster, M.D., founder and director of the Massachusetts Eye Research and Surgery Institute, clinical professor of ophthalmology at the Harvard Medical School, and president of the Ocular Immunology and Uveitis Foundation.
Iontophoresis is defined as a medical treatment that uses electronic signals to infuse medicine without injection. The iontophoresis process drives positive or negative therapeutic ions into a tissue through the use of electrodes that are placed in contact with tissue. EyeGate says it has a uniquely designed applicator that safely delivers a drug through the sclera, enabling a high percentage of the drug to reach the back of the eye with minimal leakage.
"We can obtain excellent permeability through the sclera, enabling us to deliver drugs over a larger surface area with low current density," says Stephen From, president and CEO of EyeGate. "This is far superior to topical administration, where only about 5% to 15% of the drug actually gets to the back of the eye."
EyeGate Pharma has recently been building a high-powered management team whose goal is to prove that iontophoresis can be successfully used to get medications to the back of the eye. Until now, iontophoresis has been primarily used for the transdermal delivery of pain medications and corticosteroids to treat conditions such as arthritis and carpal tunnel syndrome.
EyeGate, based in Waltham, MA, has thus far raised $16 million in venture capital funding. The company was founded in 1998 with technology licensed from Bascom Palmer Eye Institute at the University of Miami and developed by Jean-Marie Parel, PhD.
According to the company, EyeGate's transscleral iontophoresis delivery platform, the EyeGate II Delivery System, will be able to deliver a wide range of therapeutics to both the anterior and posterior chambers of the eye. The drugs must first be adapted for delivery by way of iontopheresis, which EyeGate says can be done relatively easily.
Dr. Bird Named AAO Laureate
He Has Led in Retinal Disease Research.
Alan C. Bird, MD
■ The American Academy of Ophthalmology will present its highest honor — the 2008 Laureate Recognition Award — to Alan C. Bird, MD, for his distinguished career and contributions to ophthalmology. Dr. Bird is to receive the award in November at this year's Joint Meeting with the European Society of Ophthalmology in Atlanta.
"Dr. Bird is recognized worldwide as a pioneer in ophthalmic research, teaching, and clinical medicine," said David Parke, MD, president of the Academy. "In recognition of his contributions to the profession of ophthalmology, we acknowledge the debt we all owe to him for his commitment, which has enabled many of his students to leave their mark on the field."
Dr. Bird is one of the world's experts on the treatment of retinal vascular disease and genetic and degenerative retinal disorders. He has published numerous papers, and his research has contributed to important breakthroughs in the understanding of retinal disease such as retinal dystrophies and age-related macular disease.
A native of the United Kingdom, Dr. Bird earned his medical degree from Guy's Hospital Medical School in 1961. Dr. Bird came to the United States in 1968 under a fellowship at the Bascom Palmer Eye Institute in Miami. Upon his return to London in 1969, he was appointed to the Institute of Ophthalmology as lecturer, and subsequently senior lecturer, reader, professor, and consultant at Moorfields Eye Hospital, where he established a specialized clinical service for retinal disease. At Moorfields, Dr. Bird formed a multi-disciplinary research team to investigate age-related macular disease and monogenic retinal disorders. The research programs were aided by the successful growth of the Institute of Ophthalmology of the University of London.
In addition to his work in London, Dr. Bird spent time in Africa undertaking research into river blindness. His work there led to the finding that retinal and optic nerve disease was the main cause of blindness from the disease rather than corneal scarring, leading to a new standard of treatment. He has also worked in Jamaica studying sickle cell retinopathy.
Although Dr. Bird is retired from full-time clinical practice, he continues his research and teaching as the Emeritus Professor at London University and Honorary Consultant, Moorfields Eye Hospital.
EVRS Congress Showcases New Techniques
■ In perhaps the largest gathering of its kind to take place in continental Europe, more than 700 retinal specialists hailing from 69 countries met in Prague for the 8th congress of the European Vitreoretinal Society from September 6th to the 9th. The city's opulent Municipal House — the Art Nouveau home of the Czech National Symphony Orchestra — hosted more than 900 attendees, comprised of retinal physicians, their guests, and industry executives. This year's attendance represents a 10% increase over that of the 2007 conference in Venice, says Didier Ducournau, MD, EVRS president and prime mover behind the society and its annual congress.
Befitting Prague's Bohemian heritage of encouraging artistic endeavors that challenge conventional norms, the conference highlighted innovation in technique rather than presentations of clinical trial data typical of other gatherings. "As all the attendees are really involved in the retina field, they are not coming to receive an overview of the specialty," says Dr. Ducournau. "They consider themselves artisans and they share their tricks and techniques as artisans usually do, even if they are completely ‘iconoclastic’ and not authenticated by a randomized study and statistical analysis."
All presentations were the original work of EVRS members. "We do not try to promote ourselves by inviting lecturers and offering them an audience," Dr. Ducournau explains. "We are just sharing our knowledge in as modest a way as possible. This difference is fundamental and explains the success of EVRS congresses." Hewing to the conference's theme of "My Way," each of the 100+ presentations by more than 60 EVRS members showcased an individualistic approach to a clinical or surgical challenge. Topics discussed during the 3.5-day program included minimally invasive surgery, vitrectomy, membrane peeling, luxated IOL recovery, macular surgery, retinal reattachment, diagnostic imaging, AMD therapy, diabetic retinopathy, and many more.
Attendees were asked to vote on the uniqueness and usefulness of each presentation; highest rated was "A New Method to Improve the Application of Dyes on the Retinal Surface Without Fluid-Air Exchange," by Martin Schmid, MD of Lucerne, Switzerland. As in years' past, EVRS will post audio and video recordings of all presentations on its Web site, www.evrs.org, in the coming months.
Also in Prague, EVRS unveiled a patient-education DVD with 3D animations of pathologies and their treatments, and a Wikipedia-like Web site called EVpedia.org aimed at "collating all of the techniques, philosophies and various tricks of the trade available for medical and surgical retina," says Dr. Ducournau. Both the DVD and Web site are free to EVRS members.
The 9th EVRS Congress — which will take place September 5-9, 2009 in Marrakech, Morocco — will match up presenters who follow conventional approaches with those who have adopted newer trends. "We will certainly see that in our everyday lives all of us use a mixture of innovative and conservative strategies," says Dr. Ducournau. Exploring the risk-benefit considerations when evaluating a new trend or technique will be the focus of the presentations, he says. Next year's program will also include smaller sessions the day before the conference intended to foster a more free-spirited discussion, particularly among younger members who may be reluctant to contribute to the general session.
|■ Neurotech drug is fast-tracked. Neurotech Pharmaceuticals Inc., a privately held biotechnology company focused on the development of therapeutics for chronic retinal diseases, said the FDA has granted Fast Track designations for NT-501 for the treatment of visual loss in retinitis pigmentosa (RP) and dry AMD.|
NT-501 is an intraocular, cell-containing polymer implant designed to provide continuous, long-term, release of the therapeutic protein Ciliary Neurotrophic Factor (CNTF) directly into the back of the eye by means of the company's proprietary encapsulated cell technology. The company says that CNTF, a neurotrophic factor, has the ability to rescue dying retinal photoreceptors and protect them from degeneration.
"We remain on track to announce top-line results from our 2 phase 2/3 studies in RP and our phase 2 study in dry AMD by early 2009," said Ted Danse, president and CEO of Neurotech. "The receipt of Fast Track designations for NT-501 in these indications is an important component in our ongoing product development strategy, allowing us to potentially accelerate our 2 clinical development programs as we seek to provide much needed treatment options for patients facing these devastating diseases."
■ Milestone for CZM. Carl Zeiss Meditec announced that it now has more than 10,000 OCT units installed worldwide. These units include the Cirrus HD, the Stratus, and the Visante.
■ OSI ends financial commitment to Macugen. In closing what OSI Pharmaceuticals CEO Colin Goddard, PhD, called a "disappointing chapter" in his company's history, OSI has ended the ongoing financial losses caused by its 2005 acquisition of Eyetech Pharmaceuticals and its wet AMD treatment Macugen. OSI did so by transferring its Macugen franchise to Eyetech Inc., a new business formed by former Eyetech Pharmaceuticals sales executives.
Dr. Goddard said the deal is "focused on delivering participation for OSI in any successful turnaround situation" for Macugen. "The transaction removes uncertainty surrounding the brand's future and offers the opportunity for the new co-team to launch the recently FDA-approved Luer-lock (syringe) presentation of the product," said Dr. Goddard.
The Eyetech acquisition was controversial from the day it was announced, with the announcement causing a major 1-day drop in OSI's stock price. Skeptical investors had correctly divined that the impending approval of Genentech's Lucentis, which had highly impressive clinical trial results, would negatively impact the market for already-approved Macugen.
OSI's overall losses from its venture into eye care, including the initial cost of the Eyetech Pharmaceuticals acquisition and operational losses following the acquisition, are difficult to estimate, as the company is reticent to discuss specific numbers. However, the loss runs well into the hundreds of millions dollars. On the plus side, OSI has co-developed Tarceva, a successful drug for the treatment of lung and pancreatic cancer.
■ Medicare fee "fix" is no solution. Although Sen. Edward Kennedy made an emotional return to the Senate following brain surgery to cast a key vote that helped reverse an imminent 10.6% cut in Medicare physician fees, the recent action by Congress only bought some time to work out a permanent resolution to the fee issue.
The fee fix replaced the cuts scheduled to go into effect in July with an 0.5% fee increase for the last 6 months of this year and a 1.1% fee increase for all of 2009. However, unless the current formula for determining Medicare physician fees is changed, recent temporary fixes by Congress have only borrowed funds from future years and will translate into a whopping 21% fee reduction on Jan 10, 2010.
Organizations representing physicians, including the American Medical Association, unleashed a massive grassroots publicity campaign that resulted in overwhelming Congressional approval of the fee fix and an override of President Bush's veto of the Medicare bill.
Both Republicans and Democrats have said that they want to change the current Medicare physician fee formula, which dictates what many experts call an unrealistic "sustainable growth rate" for spending on doctors. However, the two parties have not yet come close to reaching an agreement on a new formula that would set fees at a level of reimbursement in line with the real costs of practicing medicine.
■ Marco markets MacuScope. The MacuScope instrument from MacuChek and the MacuHealth LMZ3 supplement from MacuHealth (formerly AdMed), are now exclusively marketed and sold in the US through Marco Ophthalmic, Inc. The MacuScope is a diagnostic tool that measures macular protective pigment and helps to identify individuals who are at risk for AMD.
■ FDA warns on unapproved BSS. The FDA has warned companies to stop selling unapproved versions of balanced salt solution, used to irrigate the eye during ophthalmic surgery. Baxter Healthcare and Hospira are among the makers of unapproved versions, FDA officials said. Alcon and Akorn sell approved versions of the eye solution. Those will remain on the market.
Companies selling unapproved product "have bypassed the requirements of the law and put consumers at risk," said Deborah Autor, director of compliance in the FDA's drugs center. Baxter and Hospira said they would comply with the order to stop selling the unapproved solution.
The FDA has received more than 300 reports of problems, including permanent vision loss and eye inflammation, in patients treated with the eye solution since 1969, agency officials said. Inspections found contaminants and other product defects in some cases. RP