CrystalGenomics, Inc. (Seoul, Korea) and CG Pharmaceuticals, Inc. (Emeryville, California), a biopharmaceutical company with 3 clinical stage candidates, has announced that the first patient has been enrolled for a Phase 2b clinical study of CG100649, CrystalGenomics' clinical stage novel NSAID candidate, in patients with knee or hip osteoarthritis (OA).
CG100649 is a first-in-class NSAID drug candidate that is a dual inhibitor of COX-2 and carbonic anhydrase (CA). CG100649's interaction with carbonic anhydrase in red blood cells provides it with a novel "tissue-specific" transport mechanism that is designed to deliver sustained levels of drug to inflamed tissues, while maintaining low systemic exposure. Its unique dual COX-2 and CA binding properties are designed to provide potentially superior safety to cardiovascular, renal, and gastrointestinal tissues compared to traditional NSAIDs or COX-2 inhibitor drugs.
An earlier placebo-controlled Phase 2a efficacy study in hip and knee in 248 OA patients in Europe showed that a 1.2 mg daily dose provided a highly significant efficacy profile vs. the three major OA symptoms of pain, stiffness, and physical disability. Although this was not an active-comparator trial, the efficacy profile of CG100649 appeared to be at least as favorable as other COX-2 drugs. This prompted CrystalGenomics to conduct a supra-threshold Phase 1 Multiple Ascending Dose (MAD) study in healthy subjects last year that showed that higher doses of CG100649 (2, 4, or 8 mg per day) are likely to provide even higher levels of efficacy while maintaining CG100649's favorable safety profile.
The current Phase 2b study is a double-blind, randomized, multicenter, non-inferiority, repeat dose study of CG100649 versus celecoxib (Celebrex®) in OA patients. This is the first time that the OA efficacy of CG100649 is being tested directly against celecoxib in the same clinical trial. Considering that CG100649 had already shown a high level of efficacy at 1.2 mg per day in its Phase 2a OA study, it is anticipated that doses of 2 mg/day and 4 mg/day in the Phase 2b study should demonstrate that CG100649 is at least comparable (non-inferior) to celecoxib in terms of efficacy. If the initial hypothesis is supported, additional tests will evaluate whether CG100649 produces superior efficacy compared to celecoxib. Biomarker results from two previous clinical pharmacology studies in healthy volunteers suggest that CG100649 may produce efficacy results that are superior to celecoxib in this Phase 2b study.
In this Phase 2b study, only subjects recording average pain scores of 4 to 8 on a 0-10 numerical rating scale will be randomized into the study. Study participants will then receive 28 daily doses of either 2 mg/day or 4 mg/day of CG100649, or 200 mg/day of celecoxib. Anti-arthritic efficacy will be evaluated using the standardized Western Ontario and McMaster Universities (WOMAC) OA Index and the WOMAC subscales that measure pain, stiffness, and physical function.
According to Dr. Joong Myung Cho, President & CEO of CrystalGenomics, "This is an important milestone for CrystalGenomics and OA patients worldwide as we will be generating very exciting efficacy data against Celebrex, a multi-billion dollar OA drug that has been one of the pharmaceutical industry's best answers to combat OA symptoms. However, there is still great unmet medical need in this area as Celebrex and other NSAIDs fall short in either efficacy and/or safety in many patients who continue to suffer from the disabling symptoms of knee and hip osteoarthritis. We believe that CG100649 has the potential to provide greater levels of efficacy in osteoarthritis patients while maintaining a high level of cardiovascular and GI safety. We hope that successful completion of this Phase 2b study will position CG100649 as the leader among the next generation of NSAIDs for treating pain and disability in patients with moderate-severe osteoarthritis."