Genaera Corp. mapped out its pivotal development plans for Evizon (squalamine lactate), courtesy of a special protocol assessment with the FDA, which include a pair of Phase III trials for choroidal neovascularization associated with age-related macular degeneration (AMD).
"For us, this is a critical first step and an exciting milestone," Genaera President and CEO Roy Levitt said. "We are aggressively trying to develop this compound."
The Plymouth Meeting, Pa.-based company also is working to prominently position the compound in a market with potential competition: two anti-VEGF products, Macugen (pegaptanib, from Eyetech Inc. and Pfizer Inc.) and Lucentis (ranibizumab, from Genentech Inc. and Novartis Pharma AG), as well as Visudyne (verteporfin, from QLT Inc. and Novartis). Among that gaggle of treatment options, Evizon stands out because it's a systemic agent that is non-invasive to the eye, while Macugen and Lucentis are delivered via intravitreal injections. Visudyne is a photodynamic therapy.
"It's becoming a more competitive landscape in the AMD area because of the huge market potential for a product that's successful," Levitt said, noting that Genaera's drug can be delivered at home by way of an injection into a patient's arm and can be used to treat two affected eyes at once due to its systemic nature. "About a third to half of these wet AMD patients actually have both eyes affected, and the vast majority of our Phase II patients recruited to date have two affected eyes."
Evizon's global registration studies will follow identical protocols and enroll patients with predominantly classic, minimally classic and occult forms of wet AMD, the leading cause of legal blindness among adults age 50 or older in the developed world. They will be randomized to receive one of two Evizon doses, 40 mg or 20 mg, or placebo, in the multicenter, double-masked trials.
Administrations are scheduled weekly for four weeks, followed by maintenance doses every four weeks until the 104th week. Photodynamic therapy will be allowed for all patients if deemed necessary by the study physician.
An intracellular agent, Evizon is specific and selective in blocking all subtypes of VEGF, as well as other growth factors tied to angiogenesis. The product also inhibits integrin expression and reverses cytoskeletal formation, resulting in endothelial-cell inactivation and apoptosis.
The total number of patients enrolled in each study will be based upon analyses of data from existing and ongoing Phase II trials, as agreed upon with the FDA.
The primary Phase III objectives are to demonstrate Evizon's safety and significant clinical benefit on visual acuity at one year in the study eye, as measured by the Early Treatment Diabetic Retinopathy scoring system. Secondary analyses include evaluation of changes in visual acuity from baseline in the study eye at two years, change in visual acuity in fellow eyes affected with wet AMD and quality of life.
"One year is a key interim analysis," Levitt said, "because the agency has defined one year of treatment as the minimum for filing, approval and commercialization, if one should show a statistically significant improvement for vision."
The first of the pivotal studies will begin imminently, he added, and the second will get under way by the end of the year.
Evizon is in three ongoing Phase II studies, all of which are being held in the U.S. One is testing three different doses (10 mg, 20 mg or 40 mg) over four months; another is evaluating the same three doses with initial concomitant photodynamic therapy with Visudyne; the last is comparing 20 mg or 40 mg of Evizon to placebo. With the Phase II data maturing and Phase III about to begin, Genaera is generating a broad portfolio with which to attract partners. Executing such a deal remains high on the company's priority list, Levitt said, noting that agreements could cover U.S. and/or overseas territories. In the U.S., there are about 200,000 new wet AMD diagnoses annually and about 500,000 worldwide. Genaera also expects a partnership to lead to expanding the drug's use in other indications, such as back-of-the-eye uses or oncology.
Compared to potential competitors at equivalent development stages, Levitt said Evizon has matched or exceeded "the best data to date for an anti-angiogenic." He added that among late-stage patients, the product has been able to improve vision, which also is true in early stage patients, in whom vision also has been stabilized. "Virtually everyone has benefited from the treatment," Levitt said, "regardless of the stage of the lesions, their size or subtypes."
The FDA has labeled Evizon a fast-track product, and also selected it for the Continuous Marketing Application Pilot 2 program.
Beyond Evizon's late-stage development, Genaera remains focused on a couple of other clinical programs. In conjunction with Cystic Fibrosis Foundation Therapeutics Inc., of Rockville, Md., a pivotal Phase II trial of Lomucin is scheduled to soon begin in cystic fibrosis patients. It will be supported through study-specific funding of up to about $2.4 million. In addition, other potential indications for the oral mucoregulator drug include chronic bronchitis.
Through funding from the National Institutes of Health, squalamine is in a Phase II trial for prostate cancer, and by way of partnership funding from MedImmune Inc., of Gaithersburg, Md., an anti-interleukin-9 antibody is in development for asthma. It just concluded an initial Phase I trial and could enter Phase II late this year or early next year.
On Monday, Genaera's stock (NASDAQ:GENR) gained 5 cents to close at $1.62.