CombinatoRx Reports Phase 2 Data on CRx-150 in Human Inflammatory Disease Model.CAMBRIDGE, Mass. -- In the third to last sentence of the first graph, IFN-a should read: IFN-gamma. The corrected release reads: COMBINATORX REPORTS PHASE 2 DATA ON CRX-150 IN HUMAN INFLAMMATORY DISEASE MODEL -- CRx-150 Hits Secondary Endpoint With Significant Reduction in Acute CRP C-reactive protein (CRP) A protein present in blood serum in various abnormal states, like inflammation. Mentioned in: Pelvic Inflammatory Disease CRP, n.pr See C-reactive protein. , But Not Primary Endpoint of Chronic CRP, Data to be Presented at Gordon Conference on Periodontal Disease Periodontal Disease Definition Periodontal diseases are a group of diseases that affect the tissues that support and anchor the teeth. Left untreated, periodontal disease results in the destruction of the gums, alveolar bone (the part of the jaws where -- CombinatoRx, Incorporated (NASDAQ NASDAQ in full National Association of Securities Dealers Automated Quotations U.S. market for over-the-counter securities. Established in 1971 by the National Association of Securities Dealers (NASD), NASDAQ is an automated quotation system that reports on : CRXX) today announced preliminary results of its randomized ran·dom·ize tr.v. ran·dom·ized, ran·dom·iz·ing, ran·dom·iz·es To make random in arrangement, especially in order to control the variables in an experiment. , blinded, placebo-controlled clinical trial of CRx- 150 in patients with periodontitis periodontitis Inflammation of soft tissues around the teeth (see tooth). Poor dental hygiene leads to deposition of bacterial plaque on the teeth below the gum line, irritating and eroding nearby tissues. , a chronic infectious disease Infectious disease A pathological condition spread among biological species. Infectious diseases, although varied in their effects, are always associated with viruses, bacteria, fungi, protozoa, multicellular parasites and aberrant proteins known as prions. with an inflammatory component, associated with elevation of systemic inflammatory markers. This trial was designed to determine how immuno-modulating agents such as CRx-150 would affect various systemic inflammatory markers in individuals with periodontitis in both the acute and chronic phase of immunoinflammation. CRx-150 did not reduce C-reactive protein C-Reactive Protein Definition C-reactive protein (CRP) is a protein produced by the liver and found in the blood. Purpose C-reactive protein is not normally found in the blood of healthy people. (CRP) in the chronic inflammatory phase, the primary endpoint of the trial, as measured at day 42 prior to SRP SRP - A data link layer protocol. . CRx-150 did reduce CRP in the acute inflammatory phase compared to placebo (p = 0.026), a secondary endpoint of the trial, as measured on day 43 of treatment and within 24 hours following scaling and root planning (SRP) of a subject's teeth. Analysis of the effect of CRx-150 on immuno-inflammatory cytokines Cytokines Chemicals made by the cells that act on other cells to stimulate or inhibit their function. Cytokines that stimulate growth are called "growth factors. , another set of secondary endpoints, demonstrated that the CRx-150 treated group also exhibited a non-statistically significant trend towards reduced acute release of TNF-a and IL-6 within 24 hours after SRP as compared to the placebo group. There were small or no differences between CRx-150 and placebo for the other inflammatory markers measured including IL-1, IL-8, IL-12 and IFN-gamma. CRx-150 was generally well tolerated and there were no serious adverse events reported. The most common adverse event in the study reported as related to the CRx-150 treated group was headache, a known side effect of dipyridamole dipyridamole /di·py·rid·a·mole/ (di?pi-rid´ah-mol) a platelet inhibitor and coronary vasodilator used to prevent thromboembolism associated with mechanical heart valves, to treat transient ischemic attacks, and as an adjunct in . Data from this CRx-150 trial are being presented in a poster entitled "Effects of CRx-150 on Chronic and Acute Release of Inflammatory Markers in Patients with Periodontitis, a Randomized Placebo-Controlled Clinical Trial", F. D'Aiuto, etal., at the Gordon Research Conference on Periodontal Diseases, June 4-9, 2006 in Barga, Italy. "By blunting the spike in CRP that occurs immediately following SRP, CRx-150 has demonstrated its ability to effectively modulate the release of an important validated inflammatory marker," said Dr. Jan Lessem, Chief Medical Officer of CombinatoRx. "Further study of CRx-150 will be required to understand the magnitude of its effects, given the activity in the acute phase of this model, and we look forward to results of the CRx-150 Phase 2 trial in patients with rheumatoid arthritis rheumatoid arthritis Chronic, progressive autoimmune disease causing connective-tissue inflammation, mostly in synovial joints. It can occur at any age, is more common in women, and has an unpredictable course. expected in the first half of 2007," commented Alexis Borisy, President and CEO (1) (Chief Executive Officer) The highest individual in command of an organization. Typically the president of the company, the CEO reports to the Chairman of the Board. of CombinatoRx. "Overall we are very pleased that four of the six trials on which we have reported Phase 2 data this year have now shown translation of activity into humans." About the Trial Design This clinical trial was a blinded, placebo-controlled, randomized study of the effect of an 8-week treatment of CRx-150 compared to placebo in a 1:1 ratio. The primary endpoint was a reduction in CRP from baseline to day 42. Secondary endpoints of the study included changes in CRP levels following SRP, reduction in periodontal pocket depth and ability to modulate a panel of inflammatory cytokines. Patients were enrolled into the trial with severe periodontitis, defined as a minimum of 10 pockets between the teeth and gum measuring greater than or equal to 5mm in depth with at least 4 pockets greater than or equal to 6mm. Ten percent of all the pockets must have been shown to bleed on probing. Baseline CRP levels upon enrollment had to be greater than 1.5mg/L. Overall median CRP levels at study baseline were 3.4 mg/L. CRx-150 was dosed in this trial using a single dose of dipyridamole and two different doses of amoxapine. Patients received the first ratio for the first two weeks of treatment and the second ratio for the following six weeks. SRP of the subjects' teeth was conducted on day 42. Inflammatory cytokine Cytokine Any of a group of soluble proteins that are released by a cell to send messages which are delivered to the same cell (autocrine), an adjacent cell (paracrine), or a distant cell (endocrine). levels were measured periodically throughout the study. Fifty-six patients were enrolled in the trial at a single study center in London, England. About CRx-150 CRx-150 is a novel orally available syncretic syn·cre·tism n. 1. Reconciliation or fusion of differing systems of belief, as in philosophy or religion, especially when success is partial or the result is heterogeneous. 2. drug candidate in Phase 2 clinical development for immuno-inflammatory diseases. A syncretic drug comprises two compounds that are designed to act synergistically syn·er·gis·tic adj. 1. Of or relating to synergy: a synergistic effect. 2. Producing or capable of producing synergy: synergistic drugs. 3. through multiple pathways to provide a novel therapeutic effect which neither component alone can achieve. CRx-150 contains low doses of amoxapine and dipyridamole, neither of which is indicated for the treatment of immuno-inflammatory disease on its own, but which have been shown in preclinical studies preclinical studies, n.pl a term used to describe research done before a clinical study. May be laboratory or epidemiologic research. to act synergistically to modulate cytokine production. CRx-150 was discovered using the CombinatoRx combination High Throughput Screening (cHTS(TM)) technology and would be developed in a unique formulation for the treatment of immuno-inflammatory diseases. CRx-150 is currently being evaluated in an ongoing Phase 2 clinical trial phase 2 clinical trial Phase 2 study. See Phase study. in patients with rheumatoid arthritis. CRx-150 is one of a portfolio of six product candidates that CombinatoRx is currently testing in Phase 2 clinical trials. About Periodontitis and CRP Periodontitis is a bacterial disease of the gums with an inflammatory component that is associated with an increase in plasma CRP, an acute phase protein Acute-phase proteins are a class of proteins whose plasma concentrations increase (positive acute phase proteins) or decrease (negative acute phase proteins) in response to inflammation. This response is called the acute-phase reaction (also called acute phase response). and marker of systemic inflammation. A relationship between inflammatory processes and elevation of CRP has been established in periodontitis and in other immuno-inflammatory diseases including rheumatoid arthritis, inflammatory bowel disease inflammatory bowel disease n. Abbr. IBD Any of several incurable and debilitating diseases of the gastrointestinal tract characterized by inflammation and obstruction of parts of the intestine. , hand osteoarthritis osteoarthritis or osteoarthrosis or degenerative joint disease Most common joint disorder, afflicting over 80% of those who reach age 70. It does not involve excessive inflammation and may have no symptoms, especially at first. and polymyalgia rheumatica Polymyalgia Rheumatica Definition Polymyalgia rheumatica is a syndrome that causes pain and stiffness in the hips and shoulders of people over the age of 50. . Periodontal disease and therapy represents a novel inflammatory human model to study inflammation and CombinatoRx has initiated a series of Phase 2 clinical trials with several immuno-modulating drug candidates, including CRx-102, CRx-119, CRx-150 and CRx-139 to determine their impact on various inflammatory markers in individuals with periodontitis. Preliminary CRx-119 data was released in April 2006 and preliminary CRx-102 data was released in May 2006. CombinatoRx plans to present a comparative analysis of the panel of immunomodulating cytokines from these periodontitis clinical trials later this year. About CombinatoRx CombinatoRx, Incorporated is a biopharmaceutical company focused on developing new medicines built from synergistic combinations of approved drugs, designed to attack disease on multiple fronts. CombinatoRx applies its proprietary combination drug discovery technology to identify new combination product candidates in a number of disease areas, including immunoinflammatory disease, oncology, metabolic disease, neurodegenerative disease, and infectious disease. We are currently developing a portfolio of six product candidates targeting multiple diseases which were discovered by applying our proprietary screening technology. For further information, please visit the CombinatoRx website at www.combinatorx.com. Forward-Looking Statement This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act The Private Securities Litigation Reform Act of 1995 (PSLRA) implemented several significant substantive changes affecting certain cases brought under the federal securities laws, including changes related to pleading, discovery, liability, class representation and awards fees and of 1995 concerning the clinical trial results for CRx-150, its plans for further research and development of the Company's CRx-150 product candidate, the predictive value of CRP and clinical trials in chronic adult periodontitis for other immunoinflammatory diseases, its plans with respect to the research and development of the other product candidates in its portfolio, its timeframe for the announcement of results from clinical trials of its other product candidates and its drug discovery technology. These forward-looking statements about the future development of CRx-150 and future expectations, plans and prospects of CombinatoRx involve significant risks, uncertainties assumptions, including risks related to whether a clinical trial in chronic adult periodontitis or the measure of CRP is predictive of efficacy in other immuno-inflammatory diseases, the ability of CombinatoRx to design future clinical trials of CRx-150 in other immuno-inflammatory diseases based on data from a clinical trial from a different immuno-inflammatory disease, the ability of CombinatoRx to initiate and successfully complete clinical trials of its product candidates, potential difficulty and delays in obtaining regulatory approval for the sale and marketing of its product candidates, the unproven nature of the Company's drug discovery technology, the Company's ability to obtain additional funding for its research and development and those other risks that can be found in the "Risk Factors" section of the CombinatoRx Annual Report Form 10-K on file with the Securities and Exchange Commission and the other reports that CombinatoRx periodically files with the Securities and Exchange Commission. Actual results may differ materially from those CombinatoRx projects. In addition, the forward-looking statements included in this press release represent the Company's views as of the date of this release. CombinatoRx does not undertake to update any of these forward-looking statements to reflect a change in its views or events or circumstances that occur after the date of this release. (c) 2006 CombinatoRx, Incorporated. All rights reserved. |
|
||||||||||||||||
Printer friendly
Cite/link
Email
Feedback
Reader Opinion