ORIGINAL ADVOCATE ADJUDICATION FROM 2019
INDEPENDENT ADVOCATE RE-ADJUDICATION FROM 2026
The retrospective re-adjudication of the ADVOCATE primary endpoints was performed by a newly selected and trained adjudication committee using the original data packages without modification, and no access to prior patient-level adjudication decisions. No other outcomes were assessed.4
TAVNEOS® arm = TAVNEOS® + rituximab, or cyclophosphamide (followed by azathioprine or mycophenolate mofetil‡).1
Active Control arm = prednisone taper§ + rituximab, or cyclophosphamide (followed by azathioprine or mycophenolate mofetil‡).1
*Remission was defined as achieving a BVAS of 0 and not taking glucocorticoids for treatment of GPA or MPA within 4 weeks prior to Week 26.2
†Sustained remission was defined as remission at Week 26 and at Week 52 (defined as a BVAS of 0 and no glucocorticoid use for treatment of GPA or MPA for 4 weeks before Week 52), and without relapse** between Week 26 and Week 52.2
‡If azathioprine not tolerated.1
§Prednisone taper: 60 mg/day tapered to 0 over 20 weeks.1
**Relapse was defined as the occurrence of 1 or 2 non-major items for at least 2 consecutive visits, at least 1 major item, or at least 3 non-major items based on the BVAS after a BVAS of 0 had been achieved.1
††The 2026 re-adjudication was sponsored by Amgen and conducted by Duke Clinical Research Institute.4
| TAVNEOS® arm (n = 166) | Active Control arm (n = 164) | |
|---|---|---|
| Median dose | 600 mg | 3097.5 mg |
| Mean dose | 1675.5 mg | 3846.9 |
The incidence of non-study-supplied glucocorticoid exposure was balanced between both arms. Results are descriptive.7
*Prednisone equivalent dose per patient.
CYC = cyclophosphamide; EULAR = European Alliance of Associations for Rheumatology; RTX = rituximab.
Prespecified secondary endpoint not adjusted for multiplicity and subject to post-randomization variable dependence. Results should be interpreted with caution.2
Prespecified secondary endpoint not adjusted for multiplicity and subject to post-randomization variable dependence. Results should be interpreted with caution.2
*Adapted from Jayne DRW, et al. N Engl J Med. 2021;384:599-609.
BVAS = Birmingham Vasculitis Activity Score; CI = confidence interval.
3.2
mL/min/1.73 m2 LSM difference between the TAVNEOS® and Active Control arms (95% CI, 0.3-6.1)2
Prespecified secondary endpoint not adjusted for multiplicity and should be considered exploratory. Results should be interpreted with caution.2
*Least-squares mean (LSM) change in eGFR from baseline to Weeks 26 and 52 in patients with renal involvement at baseline based on the BVAS.
BVAS = Birmingham Vasculitis Activity Score; CI = confidence interval; eGFR = estimated glomerular filtration rate; ITT = intent to treat; SEM = standard error of the mean.
5.5
mL/min/1.73 m2 LSM difference between the TAVNEOS® arm and Active Control arm (95% CI, 1.7-9.5)2
Results from this exploratory subgroup analysis should be interpreted with caution.2
8.4
mL/min/1.73 m2 LSM difference between the TAVNEOS® and Active Control arms at Week 52 (95% CI, 2.9-13.8)12
Post-hoc analysis is exploratory and has not been adjusted for multiplicity. No conclusions of statistical or clinical significance can be drawn.12
Prespecified secondary endpoint of patients with renal involvement and albuminuria at baseline; analysis not adjusted for multiplicity and should be considered exploratory. Results should be interpreted with caution.2
†Based on percentage change from baseline in uACR in patients with baseline renal involvement and baseline uACR ≥10 mg/g (52-week study period).2,10
Results from the 2019 ADVOCATE adjudication:
*Remission was defined as achieving a Birmingham Vasculitis Activity Score (BVAS) of 0 and not taking glucocorticoids for treatment of GPA or MPA within 4 weeks prior to Week 26.
†Sustained remission was defined as remission at Week 26 and at Week 52 (defined as a BVAS of 0 and no glucocorticoid use for treatment of GPA or MPA for 4 weeks before week 52), and without relapse‡ between Week 26 and Week 52.
‡Relapse was defined as the occurrence of 1 or 2 non-major items for at least 2 consecutive visits, at least 1 major item, or at least 3 non-major items based on the BVAS after a BVAS of 0 had been achieved.
Post-hoc analysis results from the 2019 ADVOCATE adjudication:
Lung Outcomes
These analyses were not prespecified. The lung manifestations evaluated included: wheeze, nodules or cavities, pleural effusion/pleurisy, infiltrate, endobronchial involvement, massive hemoptysis/alveolar hemorrhage, and respiratory failure.15,16
Post-hoc subgroup analysis is exploratory and has not been adjusted for multiple comparisons. No conclusions of statistical or clinical significance can be drawn.15
§Remission was defined as achieving a BVAS of 0 and not taking glucocorticoids for treatment of GPA or MPA for 4 weeks before Week 26.
**Sustained remission was defined as remission at Week 26 and at Week 52 (defined as achieving a BVAS of 0 and no use of glucocorticoids for treatment of GPA and MPA for 4 weeks before Week 52), and without relapse†† between Week 26 and Week 52.15
††Relapse was defined as the occurrence of 1 or 2 non-major items for at least 2 consecutive visits, at least 1 major item, or at least 3 non-major items based on the BVAS after a BVAS of 0 had been achieved.15
BVAS = Birmingham Vasculitis Activity Score.
Post-hoc subgroup analysis is exploratory and has not been adjusted for multiple comparisons. No conclusions of statistical or clinical significance can be drawn.15
‡‡Relapse was defined as the occurrence of 1 or 2 minor items for at least 2 consecutive visits, at least 3 minor items, or at least 1 major item based on the BVAS after a BVAS of 0 had been achieved.15
§§Lung relapse was defined as a reoccurrence of any lung manifestation of vasculitis on the BVAS after a BVAS of 0 was first achieved for lung manifestations of vasculitis at any time during the 52-week treatment period.15
Post-hoc subgroup analysis is exploratory and has not been adjusted for multiple comparisons. No conclusions of statistical or clinical significance can be drawn.15
Baseline demographics and treatment characteristics were generally balanced between arms and across patients with lung manifestations.15
Post-hoc analysis results from the 2019 ADVOCATE adjudication:
ENT Outcomes
These analyses were not prespecified. The ENT manifestations evaluated included: bloody nasal discharge/crusts/ulcers/granulomata; paranasal sinus involvement; subglottic stenosis; conductive hearing loss; and sensorineural hearing loss.10,11
Post-hoc subgroup analysis is exploratory and has not been adjusted for multiple comparisons. No conclusions of statistical or clinical significance can be drawn.15
***Remission was defined as achieving a BVAS of 0 and not taking glucocorticoids for treatment of GPA or MPA for 4 weeks before Week 26.15
†††Sustained remission was defined as remission at Week 26 and at Week 52 (defined as achieving a BVAS of 0 and no use of glucocorticoids for treatment of GPA and MPA for 4 weeks before Week 52), and without relapse‡‡‡ between Week 26 and Week 52.15
‡‡‡Relapse was defined as the occurrence of 1 or 2 non-major items for at least 2 consecutive visits, at least 1 major item, or at least 3 non-major items based on the BVAS after a BVAS of 0 had been achieved.15
BVAS = Birmingham Vasculitis Activity Score; ENT = ear, nose, throat.
Post-hoc subgroup analysis is exploratory and has not been adjusted for multiple comparisons. No conclusions of statistical or clinical significance can be drawn.15
§§§Relapse was defined as the occurrence of 1 or 2 minor items for at least 2 consecutive visits, at least 3 minor items, or at least 1 major item based on the BVAS after a BVAS of 0 had been achieved.15
****ENT relapse was defined as a reoccurrence of any ENT manifestation of vasculitis on the BVAS after a BVAS of 0 was first achieved for ENT manifestations of vasculitis at any time during the 52-week treatment period.15
Post-hoc subgroup analysis is exploratory and has not been adjusted for multiple comparisons. No conclusions of statistical or clinical significance can be drawn.15
Baseline demographics and treatment characteristics were generally balanced between arms and across patients with ENT manifestations.15
Prespecified secondary endpoint not adjusted for multiplicity and should be considered exploratory. Results should be interpreted with caution. The SF-36 was not specifically validated for GPA and MPA.2
*As assessed by the 36-Item Short Form Health Survey (SF-36), version 2. SF-36 scores range from 0 (worst) to 100 (best).2
†Scores reflect change from baseline (least squares mean ± standard error of the mean).10
‡Role-Physical is one of the eight SF-36 domains. It assesses the limitations in routine activities because of physical health capabilities.18
§Role-Emotional is one of the eight SF-36 domains. It assesses the limitations on routine activities because of emotional factors.18
Serious hypersensitivity to avacopan or to any of the excipients.
Hepatotoxicity: Serious cases of hepatic injury have been observed in patients taking TAVNEOS, including life-threatening events. In the postmarketing setting, vanishing bile duct syndrome (VBDS) as a consequence of liver injury, including cases with a fatal outcome, has been reported. These events occurred predominantly in Japan in patients aged 65 years and older, but VBDS may affect patients of any age or ethnicity who are receiving TAVNEOS. Obtain liver test panel before initiating TAVNEOS, every 4 weeks after start of therapy for 6 months and as clinically indicated thereafter. For patients of Japanese descent, consider more frequent laboratory testing: every 2 weeks after the start of therapy for the first 3 months, followed by laboratory testing every 4 weeks for the next 3 months of treatment, and as clinically indicated thereafter. If a patient receiving treatment with TAVNEOS presents with an elevation in alanine aminotransferase [ALT] or aspartate aminotransferase [AST] to >3 times the upper limit of normal (ULN), evaluate promptly and consider pausing treatment as clinically indicated. If AST or ALT is > 5 times the ULN, or ALT or AST > 3 times the ULN with total bilirubin > 2 times the ULN, or alkaline phosphatase ≥ 2 times the ULN, or if the patient has clinical symptoms such as jaundice or pruritus, discontinue TAVNEOS until TAVNEOS-induced liver injury is ruled out. Immediately and permanently discontinue TAVNEOS if VBDS is suspected. TAVNEOS is not recommended for patients with active, untreated, and/or uncontrolled chronic liver disease (e.g., chronic active hepatitis B, untreated hepatitis C, uncontrolled autoimmune hepatitis) and cirrhosis. Consider the risks and benefits before administering this drug to a patient with liver disease.
Serious Hypersensitivity Reactions: Cases of angioedema occurred in a clinical trial, including 1 serious event requiring hospitalization. Discontinue immediately if angioedema occurs and manage accordingly. TAVNEOS must not be readministered unless another cause has been established.
Hepatitis B Virus (HBV) Reactivation: Hepatitis B reactivation, including life-threatening hepatitis B, was observed in the clinical program. Screen patients for HBV. For patients with evidence of prior infection, consult with physicians with expertise in HBV and monitor during TAVNEOS therapy and for 6 months following. If patients develop HBV reactivation, immediately discontinue TAVNEOS and concomitant therapies associated with HBV reactivation, and consult with experts before resuming.
Serious Infections: Serious infections, including fatal infections, have been reported in patients receiving TAVNEOS. The most common serious infections reported in the TAVNEOS group were pneumonia and urinary tract infections. Avoid use of TAVNEOS in patients with active, serious infection, including localized infections. Consider the risks and benefits before initiating TAVNEOS in patients with chronic infection, at increased risk of infection, or who have been to places where certain infections are common.
The most common adverse reactions (≥5% of patients and higher in the TAVNEOS group vs. prednisone group) were nausea, headache, hypertension, diarrhea, vomiting, rash, fatigue, upper abdominal pain, dizziness, blood creatinine increased, and paresthesia.
Avoid co-administration of TAVNEOS with strong and moderate CYP3A4 enzyme inducers. Reduce TAVNEOS dose when co-administered with strong CYP3A4 enzyme inhibitors to 30 mg once daily. Consider dose reduction of CYP3A4 substrates when co-administering TAVNEOS. Co-administration of avacopan and 40 mg simvastatin increases the systemic exposure of simvastatin. While taking TAVNEOS, limit simvastatin dosage to 10 mg daily (or 20 mg daily for patients who have previously tolerated simvastatin 80 mg daily for at least one year without evidence of muscle toxicity). Consult the concomitant CYP3A4 substrate product information when considering administration of such products together with TAVNEOS.
TAVNEOS is available as a 10 mg capsule.
TAVNEOS (avacopan) is indicated as an adjunctive treatment of adult patients with severe active anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (granulomatosis with polyangiitis [GPA] and microscopic polyangiitis [MPA]) in combination with standard therapy including glucocorticoids. TAVNEOS does not eliminate glucocorticoid use.
Please see Full Prescribing Information and Medication Guide for TAVNEOS.
To report a suspected adverse event, call 1-833-828-6367. You may report to the FDA directly by visiting www.fda.gov/medwatch or calling 1-800-332-1088.
important safety information Contraindications Serious hypersensitivity to avacopan or to any of the excipients.
Warnings and Precautions Hepatotoxicity: Serious cases of hepatic injury have been observed in patients taking TAVNEOS, including life-threatening events. In the postmarketing setting, vanishing bile duct syndrome (VBDS) as a consequence of liver injury, including cases with a fatal outcome, has been reported...
References: 1. TAVNEOS [package insert]. Cincinnati, OH: Amgen Inc. 2. Jayne DRW, Merkel PA, Schall TJ, Bekker P et al; ADVOCATE Study Group. N Engl J Med. 2021;384(7):599-609. 3. Data on file, Amgen. Table 14-4.2 [117367]; 2026. 4. Data on file, Amgen. DCRI Clinical Events Classification (CEC) Charter for ADVOCATE Study [117368]; 2026. 5. Data on file, Amgen. Real-World Efficacy and Safety [118422]; 2026. 6. Data on file, Amgen. Study Supplied and Non-Study Supplied Glucocorticoid Use [91955]; 2023. 7. Supplement to: Jayne DRW, Merkel PA, Schall TJ, et al; ADVOCATE Study Group. N Engl J Med. 2021;384(7):599-609. 8. Hellmich B, Sanchez-Alamo B, Schirmer JH, et al. Ann Rheum Dis. 2024;83(1):30-47. 9. Data on file, Amgen. Table 14.2.7.1.1 [100027]; 2024. 10. Data on file, Amgen. Clinical Study Report [92070]; 2020. 11. Data on file, Amgen. Table 14.2.7.1.2 [92252]; 2023. 12. Cortazar FB, Niles JL, Jayne DRW, et al; ADVOCATE Study Group. Kidney Int Rep. 2023;8(4):860-870. 13. Kaplan-Pavlovčič S, Cerk K, Kveder R, et al. Nephrol Dial Transplant. 2003;18(suppl 5):v5-v7. 14. Harvard Health Publishing. Harvard Medical School. Medical Dictionary of Health Terms: A-C. [albumin, albuminuria.] https://www.health.harvard.edu/a-through-c Accessed September 18, 2026. 15. Specks U, Spiera RF, Fussner LA, et al; ADVOCATE Study Group. ACR Open Rheumatol. 2025;7(1):e11795. 16. Specks U, Spiera RF, Fussner LA, et al; ADVOCATE Study Group. ACR Open Rheumatol. 2025;7(1):e11795; supplementary appendix. 17. Data on file, Amgen. Table 14.2.5. [92757]; 2020. 18. Preedy VR, Watson RR, eds. Handbook of Disease Burdens and Quality of Life Measures. Springer Science+Business Media; 2010.
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