Benzinga | Feb 17, 2021 05:01PM EST

ChemoCentryx Highlights Publication In New England Journal Of Medicine Of Results Of Pivotal Phase 3 ADVOCATE Trial Of Avacopan For Treatment Of Anti-Neutrophil Cytoplasmic Autoantibody-Associated Vasculitis

ChemoCentryx, Inc., (NASDAQ:CCXI), today announced that The New England Journal of Medicine (NEJM) has published results from ADVOCATE, the pivotal Phase III study evaluating avacopan, an orally-administered selective complement 5a receptor inhibitor, for the treatment of patients with anti-neutrophil cytoplasmic autoantibody-associated vasculitis (ANCA-associated vasculitis or ANCA vasculitis). The publication also featured an editorial titled, "Avacopan -- Time to Replace Glucocorticoids?" written by Kenneth J. Warrington, M.D., Chair in the Division of Rheumatology, Department of Internal Medicine at Mayo Clinic in Rochester, Minn.

ANCA-associated vasculitis is a systemic auto-immune disease in which over-activation of the complement system further activates neutrophils, leading to inflammation and eventual 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.

"The results of the ADVOCATE trial are transformational and demonstrate the potential of avacopan to offer a substantial change in the treatment paradigm for ANCA-associated vasculitis," said Peter A. Merkel, M.D., MPH, Chief of Rheumatology and Professor of Medicine and Epidemiology at the University of Pennsylvania. "Current treatment for ANCA-associated vasculitis consists of combining months of daily glucocorticoids ("steroids" such as prednisone) with other immunosuppressive medications. Use of prednisone is associated with significant side-effects, including infections, diabetes mellitus, weight gain, and other problems. The ability of avacopan to replace prednisone and help patients achieve sustained remission is a significant and exciting advance for the treatment of patients with ANCA-associated vasculitis."

"The ADVOCATE trial clearly demonstrates avacopan's ability to improve kidney function, measured by eGFR, in ANCA-associated vasculitis, and was recently reinforced in another orphan kidney disease, C3 Glomerulopathy. This is a significant advantage over other treatment options that often come with added toxicities and will likely lead to reduced risk of kidney failure over the longer term," said David Jayne, M.D., Director of the Vasculitis and Lupus Service, Addenbrooke's Hospital in Cambridge.

The ADVOCATE trial was a global, randomized, double-blind, active-controlled, double-dummy Phase III trial in 331 patients with ANCA-associated vasculitis in 20 countries. Eligible patients were randomized to receive either avacopan or oral prednisone. In addition, all patients received standard background therapy of either: (a) rituximab for 4 weeks; or (b) cyclophosphamide for 13 weeks followed by azathioprine/mycophenolate, evenly balanced between the avacopan and prednisone groups.

The study met both of its primary endpoints, demonstrating disease remission at 26 weeks and sustained remission at 52 weeks, as assessed by the Birmingham Vasculitis Activity Score (BVAS). Specifically, BVAS remission at week 26 was achieved in 72.3% of the avacopan treated patients vs. 70.1% of subjects in the prednisone group (p<0.0001 for non-inferiority). Sustained remission at 52 weeks was observed in 65.7% of the avacopan treated subjects vs. 54.9% in the prednisone group, achieving both non-inferiority and superiority to the prednisone group (p=0.007 for superiority of avacopan).

Additionally, results published in the NEJM also show that, compared to the prednisone group, avacopan treatment:

* Reduced the risk of vasculitis relapse by 54%; there was a 10.1% relapse rate in the avacopan group compared to 21.0% in the prednisone group.

* Demonstrated greater improvement in kidney function, with a mean increase from baseline to week 52 in estimated glomerular filtration rate (eGFR) of 7.3 mL/min/1.73 m2 with avacopan therapy vs. an increase in eGFR of 4.1 mL/min/1.73 m2 in the prednisone group, and the difference between groups was 3.2 mL/min/1.73 m2 (95% CI, 0.3 to 6.1).

* Significantly lowered glucocorticoid toxicity, with avacopan therapy 39.7 vs. 56.6 in the prednisone group in the Glucocorticoid Toxicity Index (GTI) Cumulative Worsening Score with a difference between groups of ?16.8 points (95% CI, ?25.6 to ?8.0), and 11.2 with avacopan therapy vs. 23.4 for the prednisone group in the GTI Aggregate Improvement Score, with a difference between groups of ?12.1 points (95% CI, ?21.1 to ?3.2).

* Led to greater improvement in health-related quality of life, measured by the Short Form 36 (SF-36) version 2 and the EuroQOL-5D-5L instrument (both Visual Analogue Scale and EQ Index), compared to the prednisone group.

Avacopan demonstrated favorable safety results in this serious and life-threatening disease, with fewer subjects having serious adverse events in the avacopan group than in the prednisone group.

The U.S. Food and Drug Administration (FDA) is evaluating avacopan for the treatment of ANCA-associated vasculitis and has set a Prescription Drug User Fee Act (PDUFA) target goal date of July 7, 2021.