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Joint Pain Forum – News you can use!

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CombinatoRx, Incorporated (CRXX) Says Arthritis Drug Misses Primary Endpoint; Stock Falls





26 Mar 2007

CombinatoRx, Incorporated (NASDAQ: CRXX) today announced preliminary results of a phase 2 clinical trial studying CRx-139 (a synergistic combination of 3mg prednisolone and the antidepressant paroxetine) and 3mg prednisolone alone, in patients with rheumatoid arthritis (RA).

CAMBRIDGE, MA, USA | Mar 26, 2007 | CombinatoRx, Incorporated (NASDAQ: CRXX) today announced preliminary results of a phase 2 clinical trial studying CRx-139 (a synergistic combination of 3mg prednisolone and the antidepressant paroxetine) and 3mg prednisolone alone, in patients with rheumatoid arthritis (RA). This trial served two important purposes. One purpose was to determine the effect of 3mg of prednisolone alone (a very low dose) in RA and to contrast this effect with the activity previously reported with CRx-102, a synergistic combination of very low dose prednisolone and dipyridamole. The results with 3mg prednisolone confirm that the anti-inflammatory benefits previously observed in three phase 2a clinical trials with CRx-102 are due to the synergistic activity of CRx-102’s components, as opposed to an effect derived from the prednisolone component alone. Another purpose of the trial was to evaluate the activity of CRx-139 vs. prednisolone alone. CRx-139 did not show statistical significance on the primary endpoint of the trial. CRx-139 did show statistical significance on multiple other endpoints, requiring further analysis.

CRx-102 Confirmed as Superior to Prednisolone Alone and Advances on Plan in RA and OA

Comparison of treatment outcomes for CRx-102 (from previously reported results in RA) versus very low dose prednisolone alone (from the study reported here) shows that CRx-102 is superior to the 3mg of prednisolone alone. Importantly, subjects in the two studies had the same demographics and similar baseline disease status, allowing for comparison of study results. The following table summarizes the ACR 20 scores for CRx-102 and low dose prednisolone, respectively, at 6 weeks, the duration of the CRx-102 RA study.

Trial Regimen Patients Achieving ACR 20 (Per Protocol) Patients Achieving ACR 20 (Intent To Treat)

CRx-102-002 CRx-102 63% 54% CRx-139-002 3mg prednisolone 36% 37%

“This trial confirms that the strong clinical activity previously reported with CRx-102 should not be attributed to the effect of its low dose prednisolone component alone,” said Alexis Borisy, President and CEO of CombinatoRx. ”We are pleased to have this additional validation of our combination sciences approach to selective steroid amplification, and we look forward to rapidly advancing CRx-102 as our lead dissociated steroid combination for the treatment of RA and OA.”






CRx-139 Misses Primary Endpoint, Shows Significance on Multiple Other Endpoints, Requires Further Analysis

While CRx-139 was not statistically significant vs. 3mg prednisolone as measured by ACR 20 at day 70, CRx-139 did achieve statistical significance vs. 3mg prednisolone alone as measured by ACR 20 and ACR 50 at earlier time points. Full analysis of the CRx-139 data is ongoing.

In this trial, CRx-139 was generally well tolerated and there were no drug-related serious adverse events reported for subjects treated with CRx-139. The most common adverse events observed with CRx-139 that occurred with a frequency of greater than 5% (9% or less) were headache and nausea, known side effects of paroxetine, one of the two components of CRx-139.

About the Trial Design

This trial was a multi-center, blinded, randomized study evaluating the effectiveness of two doses of CRx-139 (containing 10 or 20mg paroxetine with prednisolone) and 3mg of prednisolone in a 1:1:1 ratio in subjects with active RA who were on stable disease modifying anti-rheumatic drug (DMARD) therapies. The primary endpoint was ACR 20 response at day 70. Other endpoints of the trial included ACR 50 and ACR 70 responses and DAS28 scores. Additional endpoints are being analyzed and will be presented at appropriate scientific venues.

209 patients with established RA and moderate to severe disease activity with >6 tender and >4 swollen joints were enrolled in this study. Patients had to be on a DMARD therapy (such as methotrexate or sulfasalazine) for at least 3 months and be on a stable dose of DMARD therapy for a minimum of 1 month (2 months for methotrexate) prior to enrollment. CRx-139 was dosed in this trial using 3mg of prednisolone and two different doses of paroxetine. All patients received 3mg of prednisolone alone during the first 2 weeks (baseline) and then were randomized to also receive either 10mg or 20mg of paroxetine or placebo for the following 8 weeks (combination treatment period). Each arm was then deconvoluted into the individual components (3mg of prednisolone and 10 or 20mg of paroxetine or 3mg prednisolone and placebo alone) for the remaining 4 weeks (withdrawal period).

The ACR 20 score is a standard measure developed by the American College of Rheumatology to rate RA disease improvement. Patients are classified as ACR 20 responders if they demonstrate a 20% improvement from baseline in tender and swollen joint count and at least 3 of 5 other symptom related criteria. The Disease Activity Score using 28 joint counts (DAS28) is a composite score used to monitor disease activity in RA patients.

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