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Isis Reports Positive Phase 1 Data Demonstrating ISIS-FXIRx Reduces Factor XI Activity Without Bleeding
"High levels of Factor XI increase the risk of thrombosis, aberrant blood clot formation that is responsible for most heart attacks and strokes and is the number one cause of death and disability in
In the oral presentation titled "ISIS-FXIRx, A Novel and Specific Antisense Inhibitor of Factor XI, Significantly Reduces FXI Antigen and Activity and Increases aPTT Without Causing Bleeding in Healthy Volunteers" Dr.
The study produced the following results:
- Robust, sustained, statistically significant reductions of up to 78 percent and 85 percent in Factor XI protein levels in the 200 mg and 300 mg dose cohorts, respectively. (p<0.0001)
- Robust, sustained, statistically significant reductions of up to 71 percent and 78 percent in Factor XI activity in the 200 mg and 300 mg dose cohorts, respectively. Reductions in activity were accompanied by aPTT prolongation, consistent with preclinical data. (p<0.0001)
ISIS-FXIRx demonstrated a good safety profile and was well tolerated in all subjects with no clinically significant changes in hematology, electrolytes, liver or kidney function. The most common adverse event was a low incidence of mild injection site reactions.
"Although there are a number of anti-coagulants on the market, there is still a substantial need for new and safer drugs. If the activity of ISIS-FXIRx observed in this Phase 1 study is also seen in patients, particularly without an increase in bleeding, this drug could offer a significant improvement over current standard-of-care, since most anti-coagulants result in increase in bleeding. Humans who are deficient in Factor XI have been shown to have a lower incidence of thromboembolic events. Thus, ISIS-FXIRx could also be particularly useful for patients with atrial fibrillation and acute coronary syndrome for the prevention of heart attacks and stroke," said
Also at ASH this year, Isis' scientists presented new data in non-human primates demonstrating that a 50 percent or greater decrease in Factor XI activity produced potent anti-thrombotic effects with no bleeding. These data are consistent with previously reported preclinical data in multiple models of venous and arterial thrombosis, in which antisense inhibition of Factor XI produced robust anti-thrombotic effects. In addition, Isis' scientists presented data from experimental surgery models in non-human primates with ISIS-FXIRx. In this study, treatment with ISIS-FXIRx produced a dose-dependent reduction of Factor XI activity of greater than 80 percent after four weeks of treatment with no bleeding. Furthermore, inhibition of Factor XI did not increase bleeding parameters in experimental surgery models compared to control. In contrast, in the same study, treatment with Enoxaparin produced statistically significant increases in bleeding time and loss of blood volume. These data further support the anti-thrombotic potential of reducing levels of Factor XI without an increased risk of bleeding.
"We are very encouraged with the robust and sustained reductions in Factor XI activity we observed in our Phase 1 study with no increase in bleeding even in subjects who reached undetectable levels of Factor XI. In addition, these results are consistent with our preclinical studies in which we observed potent, anti-thrombotic activity without bleeding," said
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Isis is exploiting its leadership position in antisense technology to discover and develop novel drugs for its product pipeline and for its partners. Isis' broad pipeline consists of 25 drugs to treat a wide variety of diseases with an emphasis on cardiovascular, metabolic and severe and rare/neurodegenerative diseases, and cancer. Isis' partner, Genzyme, plans to commercialize Isis' lead product, mipomersen, following regulatory approval, which is expected in 2012. Isis' patents provide strong and extensive protection for its drugs and technology. Additional information about Isis is available at www.isispharm.com.
This press release includes forward-looking statements regarding the discovery, development, activity, therapeutic potential and safety of ISIS-FXIRx. Any statement describing Isis' goals, expectations, financial or other projections, intentions or beliefs, including the planned commercialization of mipomersen, is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. Isis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Isis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Isis. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Isis' programs are described in additional detail in Isis' annual report on Form 10-K for the year ended
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SOURCE
Kristina Lemonidis, Director, Investor Relations, +1-760-603-2490, or Amy Blackley, Ph.D., Assistant Director, Corporate Communications, +1-760-603-2772, both of Isis Pharmaceuticals, Inc.