ChemoCentryx Announces Publication in The New England Journal of Medicine of Results of the Pivotal Phase III ADVOCATE Trial of Avacopan for the Treatment of ANCA-Associated Vasculitis - Seite 2

“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.