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Sirna Initiates Phase I Trial of siRNA-Based Treatment for AMD in Another Sort of First

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November, it seems, has become the month of firsts for the RNAi sector.

A few weeks ago, Acuity Pharmaceuticals reported that it had begun dosing patients in a phase I study with its siRNA therapy for age-related macular degeneration. This marked the first time an RNAi drug has been used in humans (see RNAi News, 11/12/2004).

Around the same time, Alnylam Pharmaceuticals described the publication of a paper by its researchers in Nature as the first in vivo demonstration of RNAi in mammals using a systemic delivery approach (see RNAi News, 11/12/2004).

Now, Sirna Therapeutics has come out with its own first.

The company said this week that it has begun a phase I clinical trial of Sirna-027, an siRNA-based treatment for AMD, with a patient receiving treatment at the Cole Eye Institute at Cleveland Clinic Foundation. Though the trial is second behind Acuity's in terms of getting an RNAi drug into humans, Howard Robin, Sirna's president and CEO, said in a statement that the commencement of the trial marks the first time a chemically and pharmacokinetically optimized siRNA is being administered to humans.

Sirna-027 targets vascular endothelial growth factor receptor-1, compared with Acuity's drug, which targets VEGF itself. Sirna said that it expects its phase I trial to enroll up to 30 patients at four institutions: the Wilmer Ophthalmologic Institute at Johns Hopkins University; the Cole Eye Institute; the Joint Clinical Research Center, which was developed by Harvard Medical School, the Massachusetts Eye and Ear Infirmary, and the Schepens Eye Research Institute; and the Jules Stein Eye Institute at the University of California, Los Angeles.

In September, Sirna COO Nassim Usman told RNAi News that the Bascom Palmer Eye Institute at the University of Miami School of Medicine would be one of the clinical trial sites (see RNAi News, 9/10/2004). Martin Schmieg, Sirna's CFO, told RNAi News this week that while Bascom Palmer had been interested in participating in the trial, when they reviewed the protocol, they found they would not be able to enroll [a] sufficient [number of] patients because the institute had another non-RNAi drug study already ongoing.

The Stein Institute could [meet the enrollment requirements], so it became the fourth site, Schmieg explained.

According to a statement by Roberto Guerciolini, Sirna's chief medical officer, the objectives of the phase I clinical trial are fourfold: to assess the safety and tolerability of Sirna-027; to assess the presence of Sirna-027 in plasma; to determine the range of doses for our phase 2 clinical trial; and to assess biological and anatomical changes in the retina.

Sirna has said that it expects to have top-line data from the clinical trial by the third quarter of 2005. Acuity has not publicly issued an estimated time for when data from its study might be available, but President and CEO Dale Pfost told RNAi News earlier this month that we will be reporting [on the outcome of the trial] in the latter part of next year.

- DM