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Phase 3 Trial for Squalamine Lactate in Wet Age-Related Macular Degeneration Initiated
Genaera plans two identical international Phase III studies designed to enroll subjects with predominantly classic, minimally classic and occult forms of wet AMD. Each study will be a multi-center, randomized, double-masked, controlled trial and will evaluate two systemically-administered doses of EVIZON (40mg and 20 mg) versus placebo, dosed weekly for four weeks followed by maintenance doses every four weeks until week 104. Photodynamic therapy with Visudyne® (PDT) (QLT Inc., Vancouver, Canada) will be allowed for all subjects if deemed necessary by the study physician. The total number of subjects enrolled into each Phase III study will be based upon analyses of data from the Company's existing and ongoing Phase II clinical trials, as agreed upon with the U.S. Food and Drug Administration (FDA). The Company anticipates launching its second Phase III trial (MSI-1256F-302) in the second half of 2005.
The primary objectives of these studies are to demonstrate safety and significant clinical benefit of EVIZON therapy on visual acuity at one year in the study eye (assessed by Early Treatment Diabetic Retinopathy scoring System or ETDRS). Planned secondary analyses include evaluation of changes in visual acuity from baseline in the study eye at year two and change in visual acuity in fellow eyes affected with wet AMD and quality of life at years one and two.
"The start of Phase III for EVIZON is another major milestone for the Company," commented Roy C. Levitt, MD, President and Chief Executive Officer of Genaera. "Based on our clinical testing to date, EVIZON has stabilized or improved vision with a good safety profile in most everyone we have treated, including subjects with two affected eyes. We look forward to demonstrating in these studies the numerous advantages of systemic delivery of EVIZON, which is noninvasive to the eye, including the potential to treat the commonly affected fellow eye. Ultimately, as the leading systemic anti-angiogenic investigative new drug in development for the treatment of wet AMD, we expect to verify the great potential EVIZON has to be a leading therapy in the rapidly growing AMD market."
Other Ongoing Clinical Trials
Genaera is currently conducting three Phase II trials of EVIZON in wet AMD at multiple sites throughout the United States. In October 2004, the FDA granted EVIZON Fast Track designation. In January 2005, the FDA selected EVIZON for participation in the Continuous Marketing Application (CMA) Pilot 2 program.
MSI-1256F-207 is a Phase II pharmacokinetic and safety trial that will evaluate 18 subjects with AMD at three different doses of EVIZON (10 mg, 20 mg or 40 mg) over four months. In this multi-center, open-label, parallel group study, EVIZON is administered intravenously once weekly for four weeks. Subjects were then followed out to month 4 with no further treatment after week four. Depending on their response, subjects may continue to receive EVIZON as needed for up to one additional year in a separate study (MSI-1256F-211). The Company presented previously that all subjects had preserved or improved vision through the month 4 evaluation after receiving a 40 mg dose of EVIZON once weekly for four weeks.
MSI-1256F-208 is a Phase II trial designed to evaluate the safety and clinical effects of three different doses of EVIZON (10 mg, 20 mg or 40 mg) with initial concomitant PDT treatment in 45 subjects with wet AMD. Specifically, this study will evaluate the safety and effects of systemically administered EVIZON before and after photodynamic therapy with PDT. The multi-center, randomized, controlled, masked study also includes monthly EVIZON maintenance therapy through six months, along with an additional twelve months follow-up for each subject. Enrollment in this trial is closed. The Company previously presented interim findings from this study demonstrating the initial safety of administering concomitant PDT with EVIZON. Additional results from this study are expected in the second half of 2005.
MSI-1256F-209 is the cornerstone and largest of Genaera's three Phase II studies and is designed to evaluate the safety and efficacy of EVIZON in 100 subjects with AMD over a two-year period. This Phase II multi-center, randomized, double masked, controlled study will evaluate two dose levels of EVIZON (20 mg or 40 mg) given once weekly for four weeks, followed by maintenance doses once every four weeks until week 48. At the end of 48 weeks of therapy, each subject will be followed for a further 12 months. PDT is allowed for all subjects in this study if deemed necessary by the study physician. Enrollment in this trial is closed.
For information about participation in EVIZON clinical trials, patients and physicians may call Genaera's Clinical Trial Hotline at (800) 299-9156.
EVIZON is a unique first in class synthetic small molecule administered systemically that directly interrupts and reverses multiple facets of the angiogenic process. Working within activated endothelial cells, EVIZON inhibits growth factor signaling including VEGF, integrin expression, and reverses cytoskeletal formation, thereby resulting in endothelial cell inactivation and apoptosis. Systemically administered EVIZON inhibits abnormal angiogenesis in rodent models of retinopathy of prematurity, and the development of choroidal neovascular membranes in rat models of AMD. Additional preclinical studies have demonstrated that systemic EVIZON administration is effective in reaching abnormal ocular blood vessels in primates, and leads to partial regression and inhibition of new abnormal vessels in the eye. These results support that EVIZON may have a role in the treatment of human choroidal neovascular membrane formation that underlies the pathology of wet AMD.
Wet AMD resulting from angiogenesis is the leading cause of legal blindness among adults age 50 or older in the Western world. Approximately 25 to 30 million people are affected globally and this number is expected to triple over the next 25 years.
AMD occurs in two types: the "dry" form and the more severe "wet" form. Wet AMD is caused by the growth of abnormal blood vessels, or choroidal neovascularization, under the central part of the retina, the macula. Dry AMD, or the avascular form is the more common and milder form of AMD, accounting for 85% to 90% of all cases. Dry AMD results in varying forms of sight loss and may or may not eventually develop into the wet form. Although the wet form of AMD accounts for only 10% to 15% of all AMD, the chance for severe sight loss is much greater. It is responsible for 90% of severe vision loss associated with AMD. Approximately 500,000 new cases of wet AMD are diagnosed annually worldwide. In North America alone, approximately 200,000 new cases of wet AMD are diagnosed each year.
Source: Genaera Corporation