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Opko’s Phase III Trial for RNAi-Based AMD Rx Will Study Drug in Combo With Lucentis

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Opko Health last week unveiled the design of a phase III study to evaluate its lead RNAi drug candidate, the wet age-related macular degeneration treatment bevasiranib, as a maintenance therapy for the disease in combination with Genentech’s Lucentis.
 
The trial is called COBALT for “Combination of Bevasiranib and Lucentis Therapies” for AMD. It is a phase III, randomized, double-blinded, parallel-assignment study of the RNAi drug administered either every 8 or 12 weeks as a maintenance therapy following three injections of Lucentis, according to Nathan Beeley, senior project manager of pharmaceutical product development at Opko.
 
“We’re going to compare this [regimen] to Lucentis monotherapy given every four weeks to patients with AMD,” he said at the Beyond Genome conference, held in San Francisco last week.
 
Bevasiranib, which was developed by Acuity Pharmaceuticals, is an siRNA that targets vascular endothelial growth factor. Last year, the company presented phase II data showing that the drug was safe and produced dose-dependent decreases of the lesions that characterize AMD (see RNAi News, 9/14/2006).
 
At the time, Acuity said that it would seek approval for the drug as a maintenance therapy for AMD, and that it expected to begin phase III studies in mid-2007. It appears the company is on track to meet that goal.
 
Earlier this year, Acuity merged with a private ophthalmic drug firm called Froptix and the public shell company eXegenics (see RNAi News, 3/29/2007). The resultant company, now called Opko Health, has expanded Acuity’s focus, but bevasiranib still remains the lead program.
 
Eyes Have It
 
Since AMD treatments are administered through an injection directly into the eye and therefore do not require delivery vehicles, the indication was an early favorite in the RNAi space.
 
Alnylam Pharmaceuticals had been developing an RNAi-based AMD drug, but stopped development because of stiff competition from other firms developing treatments for the condition, including Genentech (see RNAi News, 9/23/2005). 
 
Other RNAi-based AMD treatments continue through the pipeline, including Sirna Therapeutics’ Sirna-027 and Quark Pharmaceuticals’ RTP-801i, although both have been out-licensed — Sirna-027 to Allergan (see RNAi News, 10/7/2005) and RTP-801i to Pfizer(see RNAi News, 9/28/2006).
 

“As a maintenance therapy, [bevasiranib] would allow reduced injection frequencies, potentially 8- or 12-week intervals, [while reducing] the risk of adverse events because you don’t have systemic exposure.”

But given its efficacy, Genentech’s Lucentis is seen as the one to beat in the AMD field despite its once-a-month dosing schedule — an important consideration given the unpleasantness of ocular injections.
 
Rather than try to compete head-to-head with Genentech’s drug, however, Opko is looking to piggyback on its success.
 
“Lucentis, as an acute therapy, does a great job of mopping up the extracellular VEGF,” Beeley said. “However, the majority of its benefits are in the first three months, it does require an aggressive monthly injection regimen, and there are systemic safety concerns.”
 
By comparison, bevasiranib prevents production of VEGF when dosed less frequently.
 
“As a maintenance therapy, [it] would allow reduced injection frequencies, potentially 8- or 12-week intervals, [while reducing] the risk of adverse events because you don’t have systemic exposure,” he said.
 
“So now we’re working towards … taking the treatment of AMD to the next level,” Beeley added. “By this we mean reducing the injection frequencies, minimizing the risk of adverse events, and [improving] patients’ quality of life [while] reducing their office visits” for treatment.
 
Opko officials declined to provide additional comment or specify when the COBALT trial is expected to begin.