Benzinga | Dec 21, 2020 04:09PM EST

ChemoCentryx and VFMCRP Provide Topline Results From ACCOLADE Trial Of Avacopan In C3 Glomerulopathy Including Improved Estimated Glomerular Filtration Rate

* As in ANCA vasculitis, avacopan demonstrated statistically significant improvement in renal function as measured by eGFR compared to placebo over 26 weeks of blinded treatment

* The change from baseline to Week 26 in C3 Glomerulopathy Histologic Index (C3G HI) for Disease Activity (primary endpoint) was not statistically different between the two treatment groups, while the C3G HI for Disease Chronicity (measuring progression of fibrosis) shows significant benefit for avacopan versus placebo

* Avacopan safe and well tolerated in C3G patients

* ChemoCentryx and VFMCRP plan to discuss registration pathway with regulatory agencies in US and EU

* Conference call today at 4:30 pm Eastern Time

MOUNTAIN VIEW, Calif. and ST. GALLEN, Switzerland, Dec. 21, 2020 (GLOBE NEWSWIRE) -- ChemoCentryx, Inc. and Vifor Fresenius Medical Care Renal Pharma (VFMCRP) today announced topline data from the ACCOLADE clinical study, the largest, randomized, blinded, placebo-controlled trial in the ultra-rare kidney disease C3 Glomerulopathy (C3G) to date, which evaluated avacopan for the treatment of that disorder. Avacopan is a first-in-class, orally-administered selective inhibitor of the complement C5a receptor.

Patients in the multi-center ACCOLADE clinical trial were randomized to receive either 30mg of avacopan twice daily (BID) or placebo for 26 weeks in a double-blind manner. The primary endpoint of the study was defined as the change from baseline in the C3G Histologic Index for Disease Activity, as determined by a blinded analysis of kidney biopsies taken at baseline and after 26 weeks of blinded study treatment. Pre-specified secondary endpoints included changes in the estimated Glomerular Filtration Rate (eGFR) (a validated measure of overall renal function), measurement of urinary protein to creatinine ratio (UPCR), measurements of urinary MCP-1 (a marker of kidney inflammation), and the C3G Histologic Index for Disease Chronicity, a biopsy based measure of the progression of renal fibrosis which is a strong predictor for progression to end stage renal disease (ESRD) in C3G. After the initial blinded treatment period, all patients receive avacopan as part of an open label extension for a further 26 weeks. Endpoint determinations from the blinded treatment period (baseline to week 26) are presented.

"The ultra-rare disease, C3 glomerulopathy, is a progressive kidney disorder where a person's renal function inexorably declines, where we have no approved therapy, and also no clear roadmap on how to get to an approved therapy," said Thomas J. Schall, President and Chief Executive Officer of ChemoCentryx. "The data from this well-controlled, blinded placebo comparison trial provides evidence that avacopan can improve kidney function in C3G. Recall that avacopan also improved kidney function in ANCA-associated vasculitis; here again the ACCOLADE C3G data show a robust and significant increase in eGFR after 26 weeks of therapy. While eGFR was a pre-specified secondary endpoint, few experts would have advised that such an increase would or could be demonstrated in this time frame in a trial of this size. It is notable too that although our chosen primary (but unvalidated) C3G histologic index for disease activity endpoint was not entirely informative in ACCOLADE, the significant improvement in renal function demonstrated with avacopan in C3G is indeed remarkable and promising. For patients, this could mean markedly slowing or even halting kidney decline, with slower progression to dialysis or transplant. We will discuss our present data with the FDA to gain their input as to the possibility of a license in this very rare and otherwise inadequately treated disorder."

"We are pleased with the results of the ACCOLADE study," said Stefan Schulze, Chief Executive Officer of Vifor Pharma. "This data set is encouraging, demonstrating important clinical benefits in patients with this C3G kidney disease in which there is currently no approved therapy. The study further consolidates the effectiveness of avacopan in proliferative glomerular diseases and provides more evidence for the safety profile of avacopan. VFMCRP will commence discussions with the European regulatory authorities about the best possible regulatory pathway to obtain approval for the European Patients in this rare and otherwise inadequately treated disease."

Study Readouts

The primary endpoint of the study was change from baseline to week 26 in the C3G Histologic Index for Disease Activity1, comparing the changes in kidney histology from biopsy sections taken from patients characterized by elevated levels of C5b-9 complement markers in the blood at time of study entry (baseline). Biopsies, taken at baseline and after 26 weeks of treatment showed that the placebo group worsened by 38% on average in the C3G Activity Score while the avacopan group improved by 2% on average. This approximately 40% average difference between the two treatment arms did not constitute statistical significance due to the high patient to patient variability. Comparison of the C3G Activity Score of all C3G subjects (comprising those with both elevated levels of C5b-9 as well as those with normal levels of C5b-9) yielded similar results: the placebo group worsened by 26% on average in the C3G Activity Score, while avacopan therapy resulted in an improvement of 6% on average.

Importantly, those patients who received avacopan experienced significant benefits in terms of kidney function and other parameters compared to those who received placebo. These benefits, assessed as pre-specified secondary endpoints, include: