VFMCRP and ChemoCentryx announce positive topline data from pivotal phase-III ADVOCATE trial demonstrating avacopan’s superiority over standard of care in ANCA associated vasculitis
· Significantly reduced glucocorticoid toxicity
· Improved health-related quality of life measures compared to standard of care
· Improved kidney function compared to glucocorticoids containing standard of care
ST GALLEN, CH and MOUNTAIN VIEW, Calif., 26 November, 2019 - Vifor Fresenius Medical Care Renal Pharma (VFMCRP) and ChemoCentryx, Inc., (NASDAQ: CCXI) today announced positive topline data from the pivotal phase-III ADVOCATE trial of avacopan, an orally administered selective complement 5a receptor inhibitor, for the treatment of patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (ANCA-associated vasculitis or ANCA vasculitis).
This global study, in which a total of 331 patients with ANCA vasculitis were enrolled, met both of its primary endpoints, disease remission at 26 weeks and sustained remission at 52 weeks, as assessed by the Birmingham Vasculitis Activity Score, or BVAS. Remission was defined as a BVAS score of zero and being off glucocorticoid treatment for ANCA vasculitis for at least the preceding four weeks.
BVAS remission at week 26 was achieved in 72.3% of the avacopan treated subjects vs. 70.1% of subjects in the glucocorticoid standard of care control group (p<0.0001 for non-inferiority). Sustained remission at 52 weeks was observed in 65.7% of the avacopan treated patients vs. 54.9% in the glucocorticoid standard of care control group, achieving both non-inferiority and superiority to glucocorticoid standard of care (p=0.0066 for superiority of avacopan).
Importantly, subjects who received avacopan experienced additional benefits compared to those in the glucocorticoid standard of care control group. These benefits, assessed as pre-specified secondary endpoints, include:
1. Significant reduction in glucocorticoid-related toxicity
o The Glucocorticoid Toxicity Index (GTI v2) showed a significant statistical advantage in the avacopan therapy arm vs the glucocorticoid containing standard of care arm.
2. Significant improvement in kidney function in patients with renal disease at baseline;
o Avacopan group exhibited a statistically significant improvement in estimated glomerular filtration rate (eGFR) from baseline to week 26 and also to week 52 compared to the glucocorticoid standard of care control group.
3. Improvements in health-related quality of life metrics
o The avacopan group demonstrated statistically significant improvements in the majority of domains measured by the validated quality of life instrument SF-36 and version 2 at week 26 or 52.
o The avacopan group reported statistically significantly better outcomes on the EuroQOL-5D-5L instrument.
The topline safety results revealed an acceptable safety profile in this serious and life threatening disease with fewer subjects having serious adverse events in the avacopan group than in the glucocorticoid standard of care control group. A full analysis of the data is underway and expanded results are expected to be announced in the coming weeks.
“We are delighted with the positive topline data from the phase-III ADVOCATE trial for the treatment of ANCA vasculitis,” said Stefan Schulze, Vifor Pharma President of the Executive Committee and Chief Operating Officer. “By successfully meeting both primary endpoints and establishing superiority at 12 months, it confirms our belief that avacopan is a novel and better way to provide vasculitis control while reducing the risks of current standard of care and improving patient experience. This outcome is of high clinical relevance and an eagerly awaited change in the long term treatment paradigm. The result is another significant milestone in our progress towards becoming the global leader in nephrology.”
“These results exceed our expectations,” said Thomas J. Schall, Ph.D., President and Chief Executive Officer of ChemoCentryx. “Today we mark the dawn of a new and historic period in the lives of ANCA vasculitis patients. This day we have for the first time demonstrated that a highly targeted therapy aimed at the very center of the ANCA disease process is superior to the traditional approach of broad immune suppression therapy; a therapy which the present findings may make obsolete. Until now ANCA vasculitis patients have had to endure regimens that contain chronic high doses of steroids and all their noxious effects, but with today’s data it is clear that the time of making patients sick with steroid therapy in an attempt to make their acute vasculitis better may at last be over. Working with our partner VFMCRP, we plan to make regulatory submissions for full marketing approval to both the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) in 2020.”
VFMCRP has an exclusive license to commercialize the drug in all countries outside the United States. VFMCRP has granted KISSEI PHARMACEUTICAL CO LTD., an exclusive sub-license to develop and commercialize the drug in Japan.
About ADVOCATE and ANCA Vasculitis
The ADVOCATE trial of avacopan was a global double-blind double-dummied Phase III trial of 331 patients with ANCA-associated vasculitis in 20 countries.
ANCA vasculitis is a systemic disease in which over-activation of the complement pathway further activates neutrophils, leading to inflammation and destruction of small blood vessels. This results in organ damage and failure, with the kidney as the major target, and is fatal if not treated. Currently treatment for ANCA vasculitis consists of courses of non-specific immuno-suppressants (cyclophosphamide or rituximab), combined with high-dose corticosteroid administration for prolonged periods of time, which can be associated with significant adverse clinical risks.
About Avacopan
Avacopan is an orally-administered small molecule that is a selective inhibitor of the complement C5a receptor C5aR1. By precisely blocking the receptor (the C5aR) for the pro-inflammatory complement system fragment known as C5a on destructive inflammatory cells such as blood neutrophils, avacopan arrests the ability of those cells to do damage in response to C5a activation, which is known to be the driver of ANCA vasculitis. Current therapies for ANCA and other related illnesses typically include broad immunosuppression with high doses of glucocorticoids (steroids) such as prednisone or methylprednisone, which cause significant clinical risks. Avacopan therapy was designed to prevent these outcomes. Moreover, avacopan’s selective inhibition of only the C5aR1 leaves the beneficial C5a l pathway through the C5L2 receptor functioning normally.
ChemoCentryx is also developing avacopan for the treatment of patients with C3 glomerulopathy (C3G) and hidradenitis suppurativa (HS). The U.S. Food and Drug Administration has granted avacopan orphan-drug designation for ANCA-associated Vasculitis, C3G and atypical hemolytic uremic syndrome The European Commission has granted orphan medicinal product designation for avacopan for the treatment of two forms of ANCA-associated Vasculitis: microscopic polyangiitis and granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis), as well as for C3G.
About Vifor Pharma and Vifor Fresenius Medical Care Renal Pharma
Vifor Pharma Group,is a global specialty pharmaceuticals company. It aims to become the global leader in iron deficiency, nephrology and cardio-renal therapies. Vifor Pharma Group consists of the following companies: Vifor Pharma; Vifor Fresenius Medical Care Renal Pharma, a joint company with Fresenius Medical Care; Relypsa; and OM Pharma. Vifor Pharma Group is listed on the Swiss Stock Exchange (SIX Swiss Exchange, VIFN, ISIN: CH0364749348). For more information, visit www.viforpharma.com.
Vifor Fresenius Medical Care Renal Pharma Ltd., a common company of Vifor Pharma Group and Fresenius Medical Care, develops and commercialises innovative and high quality therapies to improve the life of patients suffering from chronic kidney disease (CKD) worldwide. The company was founded at the end of 2010 and is owned 55% by Vifor Pharma Group and 45% by Fresenius Medical Care. For more information about Vifor Fresenius Medical Care Renal Pharma and its parent companies, please visit www.vfmcrp.com, www.viforpharma.com and www.freseniusmedicalcare.com.
About ChemoCentryx
ChemoCentryx is a biopharmaceutical company developing new medications targeted at inflammatory and autoimmune diseases and cancer. ChemoCentryx targets the chemokine and chemoattractant systems to discover, develop and commercialize orally-administered therapies. ChemoCentryx is currently focusing on its late stage drug candidates for patients with rare diseases, avacopan (CCX168) and CCX140.
CCX140, an inhibitor of the chemokine receptor known as CCR2, is currently being developed for patients with focal segmental glomerulosclerosis (FSGS), a debilitating kidney disease. The U.S. Food and Drug Administration has granted CCX140 orphan-drug designation for the treatment of FSGS.
ChemoCentryx also has early stage drug candidates that target chemoattractant receptors in other Inflammatory and autoimmune diseases and in cancer.
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