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As Alnylam Weighs Dropping AMD Candidate, Rivals Are Buoyed By Emerging Research Data

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Alnylam was tight-lipped this week after CEO John Maraganore suggested that an increasingly competitive market might force the firm to abandon its AMD candidate.

But officials at Alnylam rival Acuity Pharmaceuticals remained upbeat about their VEGF-targeting drug, Cand5, after recent data showed that that the competing VEGF compound Lucentis, co-developed by Genentech and Novartis, may be an effective treatment for the condition.

"There's emerging consensus from ophthalmologists and retinal specialists … that there is going to be a plurality of treatments that are used for patients with wet AMD and macular edema," Chairman, President, and CEO Dale Pfost, told RNAi News this week. "For us, [the Lucentis data] is an indication that this is a rich and fertile area to be in."

Lucentis is a humanized antibody fragment designed to bind to and inhibit VEGF-A. At the American Society of Retina specialists meeting last month, Genentech presented 1-year data from a phase III study of 716 patients showing that monthly intraocular injections of the drug helped prevent vision loss. Importantly, Lucentis-treated patients also experienced an improvement in visual acuity compared with controls, whose vision continued to deteriorate.


"There's emerging consensus from ophthalmologists and retinal specialists … that there is going to be a plurality of treatments that are used for patients with wet AMD and macular edema. For us, [the Lucentis data] is an indication that this is a rich and fertile area to be in."

Genentech has also submitted the drug for a fast-track designation and said it could begin the process of seeking regulatory approval for the drug as early as the end of this year if the designation is granted.

In addition, recently disclosed data show that the big biotech's cancer drug Avastin, which also targets VEGF, has been used effectively off-label to treat AMD.

"We're encouraged by the results of what might [be] referred to as pan-VEGF approaches, which [refers] to the various isoforms of VEGF," Pfost said. "Cand5 was designed from the beginning to be a pan-VEGF approach for silencing VEGF in all of its isoforms. What we've seen [with Lucentis] is that's the appropriate approach — going after all the VEGF isoforms."

Pfost also noted that "beyond the generation of drugs that are antagonists, we believe that RNA interference can provide a significant contribution."

In May, Acuity reported that top-line data from its phase I trial of Cand5 showed the drug to have a "positive" effect, with no drug-related adverse events. No efficacy data was released at the time.

According to Pfost, Acuity's phase I program is in its "final stage … and we're in the process of preparing for our phase II" trial, which is slated to begin by year end. He said that the company will find an "appropriate venue towards the latter part of this year where we can update the community as to our findings from phase I. Maybe in a few weeks we might be able to give [an indication] as to what venue it might be."

Sirna President and CEO Howard Robin, speaking during a conference call to discuss the company's second-quarter financial results this week, concurred with Pfost's assessment of the AMD market, noting that "contrary to what is commonly cited, the market for AMD is not highly satisfied.

"We strongly believe that siRNA technology has the opportunity to be more potent and with a longer duration of effect, translating to better patient compliance then aptamers or antibodies," Robin said.

"The number of treatments for AMD are multiplying … [but] Sirna believes that RNAi could provide an important advantage and important presence in this market [by] providing a safe, potent, and easy-to-use compound," Roberto Guerciolini, Sirna's senior vice president of development and chief medical officer, added during the conference call.

Guerciolini noted that phase I data on Sirna's AMD treatment, Sirna-027, which targets VEGF receptor-1, indicates the compound is not only safe and effective, but potent enough to possibly offer a better dosing schedule than other AMD treatments including Lucentis and Macugen. Further, the drug is "amenable for utilization [in] non-invasive formulations — something that is denied to large molecules like an aptamer and monoclonal antibody."

Detailed phase I data on Sirna-027 is expected to be presented by Sirna at the American Academy of Ophthalmology annual meeting in Chicago on Oct. 16. A multi-dose, placebo-controlled phase II trial is slated to begin in the first half of 2006, possibly as early as April.

Requests for comment to Quark Biotech, another RNAi company developing an AMD treatment, were not returned by press time.

— Doug Macron ([email protected])

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