CombinatorX Announces Top-Line Results from Phase 2b Study of Synavive (CRx-102) for Knee Osteoarthritis

Paul Kidwell
617.296.3854: Office
617.680.1088: Mobile
Investor Conference Call Scheduled for Today at 8:30 am EDT

CAMBRIDGE, Mass.--(BUSINESS WIRE)--CombinatoRx, Incorporated (NASDAQ: CRXX), today announced preliminary top-line results from COMET-1 (CRx-102 Osteoarthritis Multi-center Evaluation Trial), the Company's Phase 2b clinical trial designed to evaluate the safety and efficacy of Synavive (CRx-102) in subjects with symptomatic knee osteoarthritis (OA). While there was a trend in favor of Synavive, and an observed dose-response relationship, the combination did not demonstrate statistical significance compared to placebo for WOMAC question #1 measuring pain while walking on a flat surface (the primary endpoint), nor when compared to prednisolone alone. Analyses of the full dataset from the study remain ongoing.

“Encouraging earlier data from both the Phase 2a clinical trials and molecular mechanism of action led us to have high expectations for Synavive, and although it is gratifying to see the biology of the synergy as well as steroid dissociation in this preliminary data, the results in knee osteoarthritis overall are disappointing. The results contain some observations that are difficult to reconcile, and we intend to complete additional analysis of the data in order to further our understanding of Synavive’s biology and determine appropriate next steps,” said Alexis Borisy, President and CEO of CombinatoRx. “While these outcomes are a setback for the Synavive program, we remain convinced in the power of the CombinatoRx discovery platform and approach. We have many valuable assets, including CRx-401, our product candidate for Type 2 diabetes and CRx-197 for topical dermatology, both expecting Phase 2a clinical data in the next few months, as well as programs such as CRx-191 and new emerging programs such as in B-cell malignancies and a next generation version of Synavive.”

Key study results:

Data for the study’s primary endpoint, median change in WOMAC question #1 (ITT) on pain (range from 0-100mm) calculated from baseline to day 98, are shown in the following table:

WOMAC Q1 Pain (ITT)		Placebo		Prednisolone (2.7mg)		Synavive (2.7/90mg)		Synavive (2.7/180mg)		Synavive (2.7/360mg)
Baseline		79.0mm		78.0mm		80.0mm		74.5mm		78.0mm
Day 98 Change		-24.5mm		-41.0mm		-30.0mm		-35.5mm		-43.0mm

 

WOMAC Pain Subscale (ITT) data, the other widely accepted primary pain measure based on the normalized sum of WOMAC questions #1-5 on pain (range from 0-100mm rather than 0-500mm), are shown in the following table:

Normalized WOMAC Pain Subscale (ITT) 
   
 

Normalized WOMAC Pain Subscale (ITT)		Placebo		Prednisolone (2.7mg)		Synavive (2.7/90mg)		Synavive (2.7/180mg)		Synavive (2.7/360mg)
Baseline		75.0mm		75.3mm		74.4mm		62.7mm		74.2mm
Day 98 Change		-26.8mm		-31.8mm		-29.0mm		-23.5mm		-37.2mm

 

WOMAC Stiffness Subscale (ITT) data based on the normalized sum of WOMAC questions #6-7 on stiffness (range from 0-100mm rather than 0-200mm), are shown in the following table:

Normalized WOMAC Stiffness (ITT)		Placebo		Prednisolone (2.7mg)		Synavive (2.7/90mg)		Synavive (2.7/180mg)		Synavive (2.7/360mg)
Baseline		74.0mm		76.3mm		74.8mm		64.5mm		78.5mm
Day 98 Change		-23.0mm		-33.3mm		-22.5mm		-28.3mm		-35.0mm p=0.0270*

 

*Statistical significance compared to placebo

WOMAC Physical Function Subscale (ITT) data based on the normalized sum of WOMAC questions #8-24 on physical function (range from 0-100mm rather than 0-1,700mm), are shown in the following table:

Normalized WOMAC Physical Function (ITT)		Placebo		Prednisolone (2.7mg)		Synavive (2.7/90mg)		Synavive (2.7/180mg)		Synavive (2.7/360mg)
Baseline		72.4mm		71.0mm		73.1mm		60.7mm		74.8mm
Day 98 Change		-22.2mm		-30.3mm		-27.3mm		-17.7mm		-30.4mm

Synavive was generally well tolerated and there were no serious adverse events reported. The most commonly reported adverse event was headache. At 4%, the rate of drop out from headache was evenly distributed across all active arms, including prednisolone. In addition, there was no evidence of increased hemoglobin A1c, fasting plasma glucose or triglycerides in the Synavive arms as compared to placebo. Systolic blood pressure was increased in the prednisolone alone arm (a known side effect of glucocorticoids), while the Synavive combination either reduced blood pressure or increased it to a lesser degree. Of the 279 patients enrolled, 191 (68%) completed the study. Primary reasons for discontinuation included adverse event (11%), subject request (8%) and disease progression/lack of efficacy (6%).

Subject demographics are provided in the table below. Demographics of the prednisolone arm were somewhat different from the others, especially when considering gender, race, Body Mass Index (BMI) and OA beyond target joint.

Subject Demographics

Posted: October 2008

Comments