By Doug Macron
This article has been updated to include comments from Quark's CEO.
Quark Pharmaceuticals expects to file an investigational new drug application for its siRNA-based eye-disease treatment QPI-1007 sometime in September, RNAi News has learned.
And while the drug's initial indication will be non-arteritic anterior ischemic optic neuropathy, a rare condition that can lead to permanent blindness, the company expects to ultimately develop it as a glaucoma therapy, Quark CEO Danny Zurr said this week.
News of the planned IND comes just days after Quark announced that preclinical studies indicate QPI-1007 can prevent progressive retinal ganglion cell loss, which is believed to cause the vision loss characteristic of glaucoma, in an increased ocular-pressure rat model of the disease.
Late last year, the company released data demonstrating the drug's neuroprotective activity in two different animal models: one of retinal ganglion cell death by optic nerve crush and one of cell death induced by optic nerve axotomy (see RNAi News, 10/2/2008).
In the newest study, QPI-1007 was administered two weeks after disease induction when more than 25 percent of RGCs had been lost, the company said. "Whereas RGC loss progressed in the control eyes, loss of RGCs was completely blocked in the QPI-1007-treated eyes," it added.
Though these data are encouraging, Quark plans to first pursue NA-AION with the drug since the condition, like glaucoma, is characterized by retinal ganglion cell death but is likely to face a shorter path to market, Zurr said.
According to Quark, NA-AION is caused by a blockage of blood flow to the eye and has a very rapid onset. Although there is spontaneous recovery in about 40 percent of patients, the remaining 60 percent suffer permanent vision loss, Zurr said.
Clinical trials of a glaucoma drug can take years, given the disease's slow, progressive nature, he noted. But since NA-AION comes on quickly, reaching its end stage within about 30 days, human studies can be completed in a much shorter timeframe.
Additionally, because NA-AION affects only about 8,000 people in the US each year, Quark expects to be able to receive an orphan drug designation for QPI-1007, which provides a number of incentives to the drug's developer such as an extended period of market exclusivity, and potentially fast-track status since there is no existing treatment for the condition.
At the same time, should Quark be able to get QPI-1007 on the market as an NA-AION treatment, it will "no doubt be used off-label to treat glaucoma patients," Zurr said.
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He said that Quark expects to complete its planned phase I/II study of QPI-1007 for NA-AION by late 2010 or early 2011. Depending on the results, the company could then move directly into phase III or, with approval from US regulators, commercialize the drug on a restricted basis.
Because NA-AION requires "aggressive intervention," Zurr said that the drug will likely be administered as an intravitreal injection. However, the company is in "a very advanced stage" of developing a topical delivery approach that is expected to be used when administering the drug as a glaucoma therapy, he noted.
While QPI-1007 may be Quark's next drug candidate to enter the clinic, on its heels is an siRNA-based drug for use with lung transplantation and lung injury patients, Zurr said.
Although Quark has had other agents in its pipeline for longer, an ongoing phase I/II clinical trial of the kidney injury drug QPI-1002 (formerly known as both AKIi-5 or DGFi) for the prevention of delayed graft function in patients undergoing kidney transplantation has given the company expertise in dealing with organ transplantation.
QPI-1002 is also being evaluated in two phase I/II trials for acute kidney injury in patients undergoing major cardiovascular surgery. The acute kidney injury studies and the delayed graft function trial are expected to conclude by the end of the year, Zurr noted.
This, combined with a greater understanding of how to deliver siRNAs into the lung via inhalation, has prompted Quark to move its lung disease drug to the head of the queue, he said.
"This [program will yield] the next IND," possibly by the second half of 2010, he said, although he declined to provide specific details about the effort, such as the target being pursued.
According to Quark's website, direct lung delivery of the drug candidate leads to "a prominent knockdown of its target gene in the [lipopolysaccharide]-induced lung inflammation model in mice and has shown prominent anti-inflammatory activity, reverting [lipopolysaccharide]-induced pathological features.
"Results from this model and pilot studies in ischemia-reperfusion injury in rat suggest that inhibition of this Quark target by [the drug] is a potential preventive or therapeutic method for lung indications including acute lung injury and lung transplantation," the company added.
Zurr said that Quark is also has a nascent program in cancer, which marks the company's foray into the disease.
"We have some interesting initial results, but it is still in the early stage," he noted.