Avacopan Improves Kidney Health in ANCA-Associated Vasculitis with eGFRs Less than 20

Frank Cortazar, MD
Credit: New York Nephrology Vasculitis and Glomerular Center

A subgroup analysis of patients with low estimated glomerular filtration rate (eGFR) from the ADVOCATE trial is shedding further light on the effects of avacopan (Tavneos) use on renal health in patients with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis.

Presented at the Congress of Clinical Rheumatology (CCR) East 2023 annual meeting, results of the study, which assessed data among a 50-patient subgroup from the phase trial, suggest the renal benefits observed in the overall extended to patients with a baseline eGFR of 20 mL/min/1.73m2 or less, with a greater improvements in multiple markers of kidney health, including eGFR and UACR, observed for patients receiving avacopan relative to the control group.¹

Described by the Genetic and Rare Diseases Information Center as a group of diseases characterized by destruction and inflammation of small vessels, with clinical signs varying and affecting the kidney, stomach, intestine, and lungs, the US Food and Drug Administration (FDA) estimates the prevalence of ANCA-associated vasculitis to be around 200 per 1 million individuals.^2,3 A complement 5a receptor antagonist from ChemoCentryx, which was acquired by Amgen in 2022, avacopan received approval for treatment of ANCA-associated vasculitis from the FDA in October 2021 based on the results of the phase 3 ADVOCATE trial.^4,5

A randomized, double-blind, double-dummy, controlled trial, ADVOCATE randomized a 1:1 ratio to receive oral avacopan at a dose of 30 mg twice daily or oral prednisone on a tapering schedule. Per trial protocol, all patients received either cyclophosphamide or rituximab. The trial results, which were published in the New England Journal of Medicine in February 2021, avacopan was noninferior but not superior to prednisone taper with respect to remission at week 26 and was superior to prednisone taper with respect to sustained remission at the end of the 52-week trial.⁶

The CCR East study, which was led by Frank Cortazar, MD, director of the New York Nephrology Vasculitis and Glomerular Center at Saint Peter’s Hospital-Albany, was a posthoc analysis of the trial designed with eh aim of assess changes in eGFR among patients approach the threshold for dialysis. For the purpose of analysis, 20 mL/min/1.73m2 or less at baseline was used as the criteria for inclusion.¹

A total of 27 patients from the avacopan group and 23 patients from the control group of the ADVOCATE trial met inclusion criteria. Investigators pointed out baseline characteristics were similar between treatment arms. Additionally, investigators noted the mean age of this subgroup was similar to the overall patients cohort at 66 and 61 years, respectively, but the subgroup of low eGFR patients had a higher proportion with newly diagnosed disease (88% vs 69%), myeloperoxidase-positive (84% vs 57%), and microscopic polyangiitis (72% vs 45%), and higher use of cyclophosphamide (50% vs 35%).¹

Upon analysis, results indicated the mean eGFR increased by 16.1 mL/min/1.73m2 among those in the avacopan group compared to 7.7 mL/min/1.73m2 among the control group (P=.003). When examining the final eGFR value measured during the treatment period of the trial, a 2-fold or greater increase in baseline eGFR was observed among 41% of those int the avacopan group compared to 13% in the control group (P=.030). Below is the proportion of patients who achieved eGFRs above 20, 30, and 45 mL/min/1.73m2 based on treatment arm:

eGFR Category: Avacopan vs Control¹

• >20 mL/min/1.73m2: 81.5% vs 56.5%
• >30 mL/min/1.73m2: 48.1% vs 30.4%
• >45 mL/min/1.73m2:22.2% vs 4.3%

Investigators called specific attention to a single patient who had a baseline eGFR of 17 mL/min/1.73m2, which improved to 65 mL/min/1.73m2 at week 52. Investigators also called attention the results of a safety analysis, which indicated serious adverse events occurred among 48% of those in the avacopan group and 70% of those in the control group. Additionally, just 3.7% of the avacopan group required dialysis during the 52-week period compared to 8.7% in the control group.¹

References:

1. Bashyal K, Balmuri S, Baral N, Ghitmire C, et al. Renal Recovery for Patients With ANCA-Associated Vasculitis and Low eGFR in the ADVOCATE Trial of Avacopan. Paper presented at: Congress of Clinical Rheumatology (CCR) East 2023 Annual Meeting. Destin, FL. May 4 – 7, 2023.
2. Anca-associated vasculitis - about the disease. Genetic and Rare Diseases Information Center. Accessed May 8, 2023. https://rarediseases.info.nih.gov/diseases/13011/anca-associated-vasculitis.
3. Center for Drug Evaluation and Research. FDA approves add-on drug for adults with rare form of blood vessel inflammation. U.S. Food and Drug Administration. October 31, 2021. Accessed May 8, 2023. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-add-drug-adults-rare-form-blood-vessel-inflammation.
4. Silberstein N. Chemocentryx announces FDA approval of TAVNEOSTM (avacopan) in Anca-associated vasculitis. Vasculitis Foundation. October 27, 2021. Accessed May 8, 2023. https://www.vasculitisfoundation.org/chemocentryx-announces-fda-approval-of-tavneos-avacopan-in-anca-associated-vasculitis/.
5. Amgen to acquire CHEMOCENTRYX for $4 billion in cash. Amgen. August 4, 2022. Accessed May 8, 2023. https://www.amgen.com/newsroom/press-releases/2022/08/amgen-to-acquire-chemocentryx-for-$4-billion-in-cash.
6. Jayne DRW, Merkel PA, Schall TJ, Bekker P; ADVOCATE Study Group. Avacopan for the Treatment of ANCA-Associated Vasculitis. N Engl J Med. 2021;384(7):599-609. doi:10.1056/NEJMoa2023386