Lucentis/Avastin Study Set to Start
Meeting Kicks Off Head-to-Head Trial
■ Approximately 180 investigators, clinical coordinators, and optical coherence tomography (OCT) technicians met in Philadelphia in late September in preparation for the start of the National Institute of Health-funded study that will compare the relative merits of Lucentis and Avastin for wet AMD in a head-to-head trial. The meeting was held to review trial protocols and to answer questions from medical professionals who will participate in the much-awaited study, which is expected to begin enrollment later this year.
Lucentis is FDA-approved for the treatment of wet AMD, while the colorectal cancer drug Avastin has been used off-label for the disease, showing similar efficacy. Many retina specialists advocate the approval of Avastin for wet AMD as an effective and less expensive alternative to Lucentis. Genentech, which developed both Lucentis and Avastin, is not participating in the study.
Ellen Peskin, MA, CCRP, project director at the Center for Preventive Ophthalmology and Biostatistics at the University of Pennsylvania, which is coordinating the study, said funding is in place for the trial. Estimates have placed the cost of the study at approximately $16 million.
The 2-year study will enroll 1,200 newly diagnosed wet AMD patients at more than 40 sites in the United States and Canada. Patients will be randomly assigned to 1 of 4 treatment groups. One group will receive monthly injections of Lucentis, while a second patient cohort will receive monthly injections of Avastin. A third group will begin with 3 monthly injections of Lucentis followed by additional injections "as needed" and determined by OCT imaging. A fourth group will follow the same "as needed" protocol with Avastin.
The main endpoint will be changes in visual acuity, with secondary objectives including change in lesion size, fluid found in OCT evaluation, and cost.
Daniel Martin, MD, of Emory University, is serving as the principal investigator.
|■ Alcon updates Retaane plans.|
Alcon said it will not initiate another clinical trial for Retaane as a treatment for wet AMD despite receiving an "approvable" letter from the FDA for that indication. The company said it would be difficult to recruit patients for such a study because of the current availability of other treatments for the disease.
Alcon said it will continue the AART (Anecortave Acetate Risk-Reduction Trial), which is designed to determine whether Retaane can help prevent the progression of dry AMD to the wet form of the disease. The 2,500-patient study is fully enrolled with final results expected within 3 years.
In addition, Alcon is pursuing clinical studies using anecortave acetate, the active ingredient in Retaane, as a potential treatment for glaucoma.
■ Alimera licenses compounds.
Alimera Sciences, a privately held ophthalmic pharmaceutical company, announced an exclusive worldwide agreement with Emory University in Atlanta to explore oxidative stress management — specifically the reduction of reactive oxygen species (ROS) — as a treatment for ophthalmic diseases. The agreement gives Alimera the exclusive option to license a unique class of compounds, which are NADPH (nicotinamide adenine dinucleotide phosphate reduced form) oxidase inhibitors, as a potential treatment for conditions such as dry AMD, particularly the late stage of this condition (geographic atrophy).
Increased levels of ROS, which result from oxidative stress, appear to contribute to certain pathologic conditions, including dry AMD. Alimera says that reducing ROS levels is becoming an important therapeutic strategy to treat AMD as well as other ophthalmic and nonophthalmic conditions. The company adds that while antioxidant compounds attack existing ROS, an NADPH oxidase inhibitor reduces superoxide production and, subsequently, limits the formation of ROS. The NADPH complex has long been recognized by researchers as the source of superoxide in phagocytic cells; scientists, however, are starting to appreciate its presence in other cells. Animal studies based on models of disease states, including ocular disease states, are producing evidence of the therapeutic implications of inhibiting this enzyme complex.
EyeGate Explores Electronic Drug Delivery
Study Planned for Ocular Iontophoresis.
JERRY HELZNER, SENIOR EDITOR
■ EyeGate Pharma has recently been building a high-powered management team whose goal is to prove that a noninvasive electronic drug-delivery method called 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.
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."
|Correction: In the article "Drug delivery to the posterior segment" by Daryl E. Kurz, MD, and Thomas A. Ciulla, MD, published in the September 2007 edition of Retinal Physician, in the section on Alimera Science's Medidur insert there was an omission of 1 of the 2 dosages being studied in the Fluocinolone Acetonide for diabetic Macular Edema (FAME) trial currently enrolling patients. In the trial, patients are randomized to either a 0.5 μg/day dose, a 0.2 μg/day dose, or a sham injection. Retinal Physician apologizes for this omission.|
EyeGate, based in Waltham, MA, has thus far raised $16 million in venture capital funding, with another round of funding expected next year. 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.
EyeGate says an 89-patient pilot study, using the company's first-generation delivery device, demonstrated exceptional patient tolerance with a significant decrease in inflammatory markers and a concurrent increase in visual acuity. A typical application takes less than 5 minutes and has been shown to be extremely well-tolerated in patients suffering from severe uveitis and other inflammatory ocular diseases. A clinical study utilizing the EyeGate II Delivery System to treat acute flare-ups of uveitis is scheduled to begin in the first quarter of 2008.
"We will be initiating a 40-to-60 patient, multisite study using iontopheresis to deliver a corticosteroid," says Stephen From, president and CEO of EyeGate. "Corticosteroids are small-molecule drugs so that is a logical place to start in getting medication to the back of the eye. In our lab, we are now seeing highly encouraging results in getting much larger SiRNA (small interfering ribonucleic acid) molecules to the back of the eye. No one has ever been able to get these larger molecules to the back of the eye noninvasively."
EyeGate recently announced the appointment of Paul G. Chaney to its board of directors. As chief operating officer of Eyetech Pharmaceuticals, Chaney helped shepherd the wet AMD treatment Macugen through the FDA approval process. Chaney joins Samir Patel, MD, on the EyeGate board. Dr. Patel was a co-founder of Eyetech and served as that company's chief medical officer.
Stephen From was formerly a senior executive and CFO at Centelion SAS, a biotechnology company with a phase 2 biological drug for the treatment of peripheral vascular disease. In 2006, Sanofi Aventis acquired Centelion.
Merck Expands Presence in Retina
Second Major Move in Recent Months.
■ Pharmaceutical giant Merck is making it known that it intends to be a key player in the development of therapies to treat retinal diseases.
Merck and SurModics, Inc., recently announced a license and research collaboration agreement to pursue the joint development and commercialization of the I-vation sustained drug-delivery system with triamcinolone acetonide (TA) and other products that combine Merck proprietary drug compounds with SurModics' I-vation system for the treatment of serious retinal diseases.
The agreement marks the second major move by Merck in recent months to expand its presence in the development of retinal drugs. In January, Merck paid approximately $1.1 billion in cash to acquire Sirna Therapeutics, which has been developing a treatment for wet AMD based on the use of small interfering ribonucleic acid (SiRNA) molecules.
SurModics' I-vation Intravitreal Implant is a drug-delivery system capable of delivering a variety of drugs on a sustained-release basis for well over a year. It can be implanted in a minimally invasive procedure, and may be removed once the drug has been fully released.
I-vation TA (a version of the I-vation implant formulated with the steroid TA) is currently being studied in a phase 1 human clinical trial called STRIDE (Sustained Triamcinolone Release for Inhibition of Diabetic Macular Edema). The trial is assessing the safety and tolerability of the I-vation Intravitreal Implant with TA in patients with diabetic macular edema under an Investigational New Drug application with the FDA. Positive 9-month data from the study were presented in May at the Association for Research in Vision and Ophthalmology (ARVO) annual meeting in Fort Lauderdale, FL.
"I-vation's encouraging TA phase 1 clinical trial results, along with SurModics' depth of technologies and expertise in polymers for sustained drug delivery, make SurModics a compelling and complementary development partner," said Darryle D. Schoepp, PhD, Merck's senior vice president and head of Neuroscience Research and Development.
|■ B&L buyout approved.|
Shareholders of Bausch & Lomb voted on Sept. 21 to approve the sale of the company to private equity firm Warburg Pincus for $65 a share in cash, or a total of $3.67 billion. Shareholders representing more than two-thirds of company stock voted in favor of the deal, which is expected to close in the fourth quarter.
■ VEGF-Trap milestone. Regeneron Pharmaceuticals, Inc. said it has received a $20 million milestone payment from Bayer HealthCare following dosing of the first patient in the phase 3 study of the VEGF Trap-Eye for wet AMD.
"Age-related macular degeneration continues to be one of the leading causes of blindness in adults today," said Leonard S. Schleifer, MD, PhD, president and chief executive officer of Regeneron. "Results of early phase studies have shown that VEGF Trap-Eye has the potential to be an important addition to the treatment alternatives available for patients with wet AMD."
The phase 3 study will be a non-inferiority comparison of the VEGF Trap-Eye and Lucentis. The randomized, double-masked study is expected to enroll approximately 1200 patients in more than 200 centers throughout the United States and Canada.
The VEGF Trap-Eye is a fully human, soluble VEGF receptor fusion protein that binds all forms of VEGF-A along with the related placental growth factor. The VEGF Trap-Eye is a specific and highly potent blocker of these growth factors.
■ AMD drug study. Opko Health, Inc., which now encompasses the former Acuity Pharmaceuticals, has announced the initiation of the phase 3 COBALT (Combining Bevasiranib And Lucentis Therapy) clinical trial of bevasiranib for the treatment of wet AMD. The multinational COBALT study is currently open and enrolling patients. The trial will include more than 330 wet AMD patients and will assess whether bevasiranib administered every 8 or 12 weeks is safe and has equivalent efficacy in preventing vision loss as Genentech's Lucentis administered every 4 weeks.
Bevasiranib is a first-in-class small interfering RNA (SiRNA) drug designed to silence the genes that produce VEGF. Bevasiranib is the first therapy based on RNA interference technology to advance to phase 3 clinical trials. RP