ChemoCentryx announces positive topline results for phase 2 diabetic nephropathy candidate CCX140 – December 18, 2014

California-based biopharmaceutical company ChemoCentryx announced positive topline results last week from a phase 2 trial of its chemokine receptor 2 (CCR2) inhibitor CCX140 in patients with diabetic nephropathy. The trial (ClinicalTrials.gov Identifier: NCT01447147) met its primary endpoint of a significant (p=0.02) reduction in urinary albumin/creatinine ratio (UACR) at 52 weeks with 5 mg CCX140 vs. placebo, both in addition to standard of care (treatment with an ACE inhibitor or ARB). Notably, treatment with a 10 mg dose did not provide any additional benefit compared to the 5 mg dose. However, the difference between the lower dose of CCX140 and placebo was significant at all 10 time points throughout the 52 weeks, with the greatest difference (24%) occurring at 12 weeks. In addition, treatment with CCX140 reduced the slope of decline in estimated glomerular filtration rate (eGFR) to a greater extent than standard of care alone (attenuated annual slope decline of 1.3 ml/min/1.73 m² vs. 2.3 ml/min/1.73 m²). While the eGFR results have not yet been analyzed for statistical significance, the company stressed in a following conference call that the demonstrated magnitude of improvement is comparable to that achieved with other approved diabetic nephropathy drugs. In addition, the findings demonstrated that CCX140 did not affect systemic blood pressure and was relatively well-tolerated (an overall dropout rate of 10%) with no major safety issues. As background, this phase 2 trial was originally designed as a 12-week safety study with 332 patients. The trial duration was later extended to 52 weeks under an amended protocol, with 196 patients participating, and final results included these additional efficacy endpoints.

Looking forward, management indicated that ChemoCentryx will likely seek a partner before initiating phase 3 trials and expressed optimism that interest will be high given the enormous unmet need in diabetic nephropathy. While the design of a phase 3 trial will depend on the outcome of ongoing discussions with the FDA and European regulators, management said that the trial would likely involve a few thousand patients and last approximately two to three years, with a primary endpoint related to eGFR. Diabetic nephropathy remains one of the areas of greatest unmet need in diabetes, as currently available therapies can slow the course of the disease but not reverse it. It seems unlikely that CCX140, which works primarily by attenuating abnormal inflammatory responses in the kidney, will prove to be disease-modifying but it could offer a valuable additional treatment option for many patients if results continue to be positive.  ChemoCentryx is one of many companies currently developing novel therapies for diabetic nephropathy – see the table below for an overview of the current competitive landscape.

Table 1: Diabetic Nephropathy Competitive Landscape

-- by Emily Regier, Melissa An, and Kelly Close