Abstract: SA-PO696
Integrated Safety of Avacopan in ANCA-Associated Vasculitis
Session Information
- Glomerular Diseases: Clinical, Outcomes, Trials - III
November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1303 Glomerular Diseases: Clinical‚ Outcomes‚ and Trials
Authors
- Jayne, David R.W., University of Cambridge, Cambridge, Cambridgeshire, United Kingdom
- Bekker, Pirow, ChemoCentryx Inc, San Carlos, California, United States
Background
Avacopan (TAVNEOS®) is approved as adjunctive treatment for adults with ANCA-associated vasculitis (AAV). Integrated safety data from 2 Phase 2 and 1 Phase 3 studies in 439 AAV patients is reported.
Methods
In the 3 trials, all groups received background cyclophosphamide followed by azathioprine, or rituximab; control groups received full prednisone regimen (60mg tapered to 0 over 20 weeks) plus placebo. The Phase 2 CLEAR trial (Jayne et al. 2017) had 3 groups: control (N=23), avacopan 30mg twice daily (BID)+low dose prednisone (N=22), and avacopan+no prednisone (N=22). The Phase 2 CLASSIC trial (Merkel et al. 2020) had 3 groups: control (N=13), avacopan 10mg BID (N=13), and 30mg BID (N=16). The Phase 3 trial (ADVOCATE; Jayne et al. 2021) had a control group (N=164) and a 30mg avacopan group with no oral glucocorticoid taper (N=166). The treatment period was 12 weeks in Phase 2 and 52 weeks in Phase 3. Integrated exposure-adjusted adverse event (AE) rates were calculated.
Results
439 patients were treated, 200 controls and 239 avacopan. The AE patient first incidence rate and AE rate, serious AE rate, infection event rate, and WBC count decrease AE rate were statistically lower in the avacopan compared to the prednisone group (see table).
Conclusion
In the context of avacopan’s demonstrated efficacy profile, these integrated safety results provide support for avacopan’s use in the treatment of patients with AAV.
Refs: Jayne et al. J Am Soc Nephrol 2017;28:2756; Jayne et al. NEJM 2021;384:599; Merkel et al. ACR Open Rheumatol 2020;2:662.
Exposure-Adjusted Adverse Event Rates by Treatment Group
| Exposure-adjusted rate/ 100 patient-years | Prednisone Control Groups (N=200) | Avacopan Groups (N=239) | Difference (95% CI) |
| Total exposure (patient-years)* | 195.7 | 212.3 | |
| Adverse event patient first incidence rate** | 1626 | 1328 | -298 (-583.0, -13.0) |
| Adverse event rate*** | 1251.7 | 1099.8 | -151.9 (-218.6, -85.3) |
| SAE patient first incidence rate | 60.1 | 61.6 | 1.5 (-16.5, 19.6) |
| SAE rate | 91.5 | 70.7 | -20.8 (-38.3, -3.3) |
| Discontinuation of blinded study medication due to AEs: Patient first incidence rate | 18.0 | 18.2 | 0.2 (-8.4, 8.9) |
| Discontinuation of blinded study medication event rate | 21.5 | 21.7 | 0.2 (-8.8, 9.2) |
| Infections# patient first incidence rate | 148.5 | 139.1 | -9.4 (-42.6, 23.7) |
| Infections event rate | 166.6 | 142.2 | -24.3 (-48.5, -0.1) |
| Liver function AEs#: Patient first incidence rate | 12.3 | 14.7 | 2.3 (-5.2, 9.8) |
| Liver function AE rate | 17.4 | 18.4 | 1.0 (-7.2, 9.2) |
| WBC decrease AEs#: Patient first incidence rate | 25.0 | 18.9 | -6.1 (-16.0, 3.8) |
| WBC decrease event rate | 34.2 | 22.6 | -11.6 (-22.2, -1.2) |
| Hypersensitivity AEs#: Patient first incidence rate | 58.0 | 57.7 | -0.3 (-18.1, 17.5) |
| Hypersensitivity AE rate | 61.8 | 68.8 | 6.9 (-8.7, 22.6) |
| AE=adverse event; SAE=serious adverse event; WBC=white blood cell *Exposure calculated as follow-up time for all patients in the treatment group (irrespective of whether an event occurred). **Patient first incidence calculated as number of patients with at least 1 event divided by total follow-up time per 100 patient-years Follow-up time = total time at risk (in years), defined as the sum of: (1) follow-up time in patients who did not have a treatment-emergent adverse event, and (2) time to first occurrence of the event in patients who had a treatment-emergent adverse event. ***Rate calculated as total number of events divided by total follow-up time per 100 patient-years. # Pre-specified AEs of interest; AE preferred terms identified before unblinding. Refer to Warnings in full prescribing information for TAVNEOS® that lists hepatotoxicity, hypersensitivity reactions, hepatitis B reactivation, and serious infections. | |||
Funding
- Commercial Support –