Tavneos®.C: Avacopan. I: Tavneos, as an adjunct therapy to standard immunosuppressive treatment based on rituximab or cyclophosphamide with glucocorticoids, is indicated for the treatment of adult patients with severe active ANCA vasculitis (GPA/MPA). Po: Oral intake 30 mg (3 capsules of 10 mg each) twice daily in the morning and evening with food. CI: Hypersensitivity to the active substance or any of the excipients. W/P: Hepatotoxicity; angioedema; monitoring of blood count (white blood cells); severe infections; hepatitis B virus reactivation; cardiac disorders; malignant tumours; macroglycerin hydroxystearate. P/L: Use during pregnancy and in women of childbearing age who are not using a contraceptive method is not recommended. It is not known whether Avacopan is excreted into breast milk. The benefit of breastfeeding to the child should be weighed against the benefit of treatment to the patient. UE: Very common: upper respiratory tract infection, nasopharyngitis; headache; vomiting, diarrhoea, nausea; increased liver test; decreased white blood cell count. Frequent: pneumonia, lower respiratory tract infection, influenza, bronchitis, cellulitis, urinary tract infection, herpes zoster, sinusitis, oral candidiasis, oral herpes, otitis media, rhinitis, gastroenteritis; neutropenia; upper abdominal pain; increase in blood creatine phosphokinase. Occasional: angioedema. IA: Avacopan is a substrate of CYP3A4. Co-administration of inducers or inhibitors of this enzyme may affect the pharmacokinetics of Avacopan. See SmPC. P: Tavneos 10 mg: 30 and 180 hard capsules. List B. Detailed information: www.swissmedicinfo.ch. Date of information: January 2024. Marketing authorization holder: Vifor Fresenius Medical Care Renal Pharma Ltd, St. Gallen. Distribution: Vifor Pharma Switzerland AG, CH-1752 Villars-sur-Glâne | CH-AVA-2300143
This medicinal product is subject to additional monitoring. For further information, see professional information TAVNEOS® on www.swissmedicinfo.ch.
E 01/2024 CH-AVA-2300101 v2.0
Templates for the request of cost reimbursement
TAVNEOS® is indicated as an adjunctive treatment to standard immunosuppressive treatment that includes rituximab or cyclophosphamide with glucocorticoids for the treatment of adult patients with severe, active ANCA-associated vasculitis (GPA/MPA).1
TAVNEOS® is not included in the specialties list (SL/LS).
To simplify the process on your side, we offer templates for the request of cost reimbursement which can be sent to the respective health insurance company or the medical examiner.
Download the TAVNEOS® cost reimbursement request form here
TAVNEOS®-based regimen achieved non-inferior clinical remission at Week 26 and superior sustained clinical remission at Week 52 vs a GC-based regimen1†
At Week 26, a TAVNEOS®-based regimen demonstrated non-inferiority in achieving clinical remission
vs a GC-based regimen1
p<0.001 for non-inferiority
(Difference 3.4, 95% CI, -6.0 to 12.8)
At Week 52, a TAVNEOS®-based regimen demonstrated superior sustained clinical remission
vs a GC-based regimen1
p=0.007 for superiority
(Difference 12.5, 95% CI, 2.6 to 22.3)
At Week 52, TAVNEOS®-based regimen demonstrated a NNT between 8 and 101†
TAVNEOS®-based regimen resulted in a lower absolute risk of relapse vs a GC-based regimen over 52 weeks1
Absolute risk of relapse over 52 weeks of treatment1
Twice as many patients relapsed in the GC-based regimen vs the TAVNEOS®-based regimen1
There was no pre-speci ed plan for adjustment of con dence intervals for multiplicity of the secondary end points; point estimates and 95% con dence intervals only are presented, and no de nite conclusions can be drawn from these data
Relative risk of relapse
TAVNEOS®-based regimen demonstrated a 54% relative risk reduction in relapse vs a GC-based regimen over 52 weeks1
ADVOCATE study design
52 week, international, multicentre, active-comparator, randomised, double-blind, double-dummy, controlled, pivotal phase 3 study with patients assigned to receive TAVNEOS® 30 mg twice daily (N=166) or prednisone tapering schedule for 20 weeks (60 mg per day tapered to discontinuation by Week 21) (N=164) on the top of either cyclophosphamide (followed by azathioprine) or rituximab.1
TAVNEOS®-based regimen patients received NO study-supplied GCs. Patients in both regimens could use non-study supplied GCs throughout the 52-week study at their physician’s discretion for AAV worsening or non-AAV-related reasons. Non-study supplied GCs during the screening had to be tapered to ≤20 mg per day before entering the study, and further tapered to 0 mg by the end of Week 4 of the study.3
Key inclusion and exclusion criteria3
Inclusion criteria
Exclusion criteria
≥12 years old*
Newly-diagnosed or relapsing GPA or MPA according to Chapel Hill Consensus Conference definitions
Indicated for RTX or CYC treatment
Either MPO+ or PR3+
Estimated eGFR of ≥15 mL/min/1.73m2
At least one major or 3 non-major items, or at least two renal items of haematuria and proteinuria on BVAS
Alveolar haemorrhage requiring invasive pulmonary ventilation anticipated to last beyond screening
Any other multisystem autoimmune disease
Coagulopathy or bleeding disorder
Required dialysis or plasma exchange within 12 weeks prior to screening
A kidney transplant
Had received CYC within 12 weeks prior to screening, RTX within 12 months prior to screening (or 6 months with B cell reconstitution, CD19 count >0.01x109/L), cumulative dose of IV GCs >3 g within 4 weeks, or oral GCs of >10 mg per day prednisone (or equivalent) for >6 weeks continuously prior to screening
*Adult and adolescent GPA/MPA patients participated in this study. For additional details, visit clinicaltrials.gov, study code: NCT02994927
Baseline characteristics1
TAVNEOS®-BASED REGIMEN (n=166)
GC-BASED REGIMEN (n=164)
AGE (mean±SD)
61.2±14.6
60.5±14.5
MALE no. (%)
98 (59.0)
88 (53.7)
GRANULOMATOSIS WITH POLYANGIITIS no. (%)
91 (54.8)
90 (54.9)
MICROSCOPIC POLYANGIITIS no. (%)
75 (45.2)
74 (45.1)
RELAPSED PATIENTS no. (%)
51 (30.7)
50 (30.5)
NEWLY DIAGNOSED PATIENTS no. (%)
115 (69.3)
114 (69.5)
BVAS SCORE no. (%)
16.3±5.9
16.2±5.7
GC USE DURING SCREENING PERIOD no. (%)
125 (75.3)
135 (82.3)
ORGAN INVOLVEMENT no. (%)
RENAL
EARS, NOSE, AND THROAT
CHEST
134 (80.7)
75 (45.2)
71 (42.8)
134 (80.7)
75 (45.2)
71 (42.8)
TAVNEOS-BASED REGIMEN (n=166)
AGE (mean±SD)
61.2±14.6
MALE no. (%)
98 (59.0)
GRANULOMATOSIS WITH POLYANGIITIS no. (%)
91 (54.8)
MICROSCOPIC POLYANGIITIS no. (%)
75 (45.2)
RELAPSED PATIENTS no. (%)
51 (30.7)
NEWLY DIAGNOSED PATIENTS no. (%)
115 (69.3)
BVAS SCORE no. (%)
16.3±5.9
GC USE DURING SCREENING PERIOD no. (%)
125 (75.3)
ORGAN INVOLVEMENT no. (%)
RENAL
EARS, NOSE, AND THROAT
CHEST
134 (80.7)
75 (45.2)
71 (42.8)
GC-BASED REGIMEN (n=164)
AGE (mean±SD)
60.5±14.5
MALE no. (%)
88 (53.7)
GRANULOMATOSIS WITH POLYANGIITIS no. (%)
90 (54.9)
MICROSCOPIC POLYANGIITIS no. (%)
74 (45.1)
RELAPSED PATIENTS no. (%)
50 (30.5)
NEWLY DIAGNOSED PATIENTS no. (%)
114 (69.5)
BVAS SCORE no. (%)
16.2±5.7
GC USE DURING SCREENING PERIOD no. (%)
135 (82.3)
ORGAN INVOLVEMENT no. (%)
RENAL
EARS, NOSE, AND THROAT
CHEST
134 (80.7)
75 (45.2)
71 (42.8)
Primary endpoints1
Primary
Overview of results
Achievement of clinical remission (BVAS 0 and no GC use in previous 4 weeks)
Non-inferior to GC-based regimen
(p<0.001 for non-inferiority)
Sustained remission at Week 52,defined as clinical remission at Week 26
through to Week 52
Superior to GC-based regimen
(p=0.007 for superiority)
Secondary endpoints1,3-6
Secondary
Overview of results
Change in GC-related toxicity during first 26 weeks according to the GTI
Significant reduction in GTI-CWS at Week 26
(p=0.0002); significant reduction in GTI-AIS at
Week 26 (p=0.008) vs GC-based regimen
BVAS 0 at Week 4
Similar number of patients achieved BVAS 0 at
Week 4 in both treatment groups
Change in health-related QoL scores over 52 weeks as measured by SF-36v2 and EuroQoL-5D-5L
Significant improvements in physical QoL (p=0.002 at Week 26 and p=0.018 at Week 52) and health-related QoL* vs GC-based regimen. Numerical improvement in mental QoL
In patients with renal disease at baseline, change over 52 weeks in eGFR, UACR and MCP-1:creatinine ratio
Meaningful improvements in renal function at Week 52 (p=0.029), meaningful reduction in UACR at Week 4; numerically greater reduction in MCP-1:creatinine ratio at Week 52 vs GC-based regimen
Relapse (BVAS >0) assessed in a time-to-event analysis
54% relative reduction in relapse risk over 52
weeks vs GC-based regimen
Cumulative organ damage (VDI)
Numerically similar change in VDI from baseline across both treatment groups
There was no pre-specified plan for adjustment of confidence intervals for multiplicity of the secondary end points; point estimates and 95% confidence intervals only are presented, and no definite conclusions can be drawn from these data
*Health-related QoL was measured using two scores: EQ-5D-5L VAS score and EQ-5D-5L index. Significant improvements in EQ-5D-5L VAS score were observed in the TAVNEOS-based regimen at and Week 52 vs GC-based regimen (as 95% confidence interval of the differences between the TAVNEOS®-based regimen and GC-based regimen groups does not include 0). With the EQ-5D-5L index, numerical improvements were observed at Week 26, and significant improvements were observed at Week 52 (p=0.009) in the TAVNEOS-based regimen vs GC-based regimen1,3,5
In patients with Stage 4 CKD (eGFR <30 mL/min/1.73 m2):1,6
mL/min/1.73 m2 eGFR increase in TAVNEOS®-based regimen (n=52) vs +8.2 mL/min/1.73 m2 in GC-based regimen (n=48) at Week 52 (p=0.005) (Difference 5.6, 95% CI, 1.7 to 9.5)
In patients with Stage 4/5 CKD (eGFR ≤20 mL/min/1.73 m2):6
mL/min/1.73 m2 eGFR increase in TAVNEOS®-based regimen (n=27) vs +7.7 mL/min/1.73 m2 in GC-based regimen (n=23) at Week 52 (p=0.003) (Difference 8.4, 95% CI, 2.9 to 13.8)
There was no pre-specified plan for adjustment of confidence intervals for multiplicity of the secondary end points; point estimates and 95% confidence intervals only are presented, and no definite conclusions can be drawn from these data
TAVNEOS®-based regimen demonstrated a significant reduction in GC toxicity1,4
reduction in GTI Cumulative Worsening Score (CWS) in TAVNEOS®-based regimen vs GC-based regimen at Week 26 1,4
Difference at Week 13: -11.0 (95% CI, -19.7 to -2.2)
Difference at Week 26: -16.8 (95% CI, -25.6 to -8.0)
GTI CWS increase as new toxicities are reported (e.g. worsening hypertension, infection) but do not decrease when improvements occurs 7
reduction in GTI Aggregate Improvement Score (AIS) in TAVNEOS®-based regimen vs GC-based regimen at Week 26 1,4
Difference at Week 13: -13.3 (95% CI, -22.2 to -4.4)
Difference at Week 26: -12.1 (95% CI, -21.1 to -3.2)
GTI AIS increase when toxicities are reported and decrease when improvement occurs 7
There was no pre-specified plan for adjustment of confidence intervals for multiplicity of the secondary end points; point estimates and 95% confidence intervals only are presented, and no definite conclusions can be drawn from these data
TAVNEOS®-based regimen demonstrated significant improvements in physical and health-related domains of QoL1,3,5
Significant improvements in physical QoL at Week 521,5§
Difference at Week 26: 3.10 (95% CI, 1.17 to 5.03)
Difference at Week 52: 2.35 (95% CI, 0.40 to 4.31)
Significant improvements in health-related QoL at Week 521,3**††
Difference at Week 26: 3.6 (95% CI, -0.1 to 7.2)
Difference at Week 52: 5.9 (95% CI, 2.3 to 9.6)
ADVOCATE is the first study to show a significant difference in the QoL between treatment arms1,3,5,8–10
There was no pre-specified plan for adjustment of confidence intervals for multiplicity of the secondary end points; point estimates and 95% confidence intervals only are presented, and no definite conclusions can be drawn from these data
Sign up here to learn more about managing AAV (GPA/MPA) with a TAVNEOS®-based regimen
*TAVNEOS®, as an adjunctive treatment to standard immunosuppressive treatment that includes rituximab or cyclophosphamide with glucocorticoids, is indicated for the treatment of adult patients with severe, active ANCA-associated vasculitis (GPA/MPA).11
†Clinical remission in the ADVOCATE study was defined as a BVAS 0 and no glucocorticoid use in previous 4 weeks.1
‡The NNT was calculated using https://www.statology.org/confidence-interval-difference-in-proportions-calculator/ to determine the confidence intervals for crude difference in proportions. At Week 52, the response rates were 65.7% in the TAVNEOS®-based regimen and 54.9% in the GC-based regimen. This led to a crude result of NNT = 1/(0.657-0.549) = 9.26, rounded to 10 patients. Using the adjusted model and the estimated common difference, the NNT = 1/0.125 = 8. In conclusion, the NNT is between 8 and 10 patients at Week 52.1
§A numerical improvement was seen in mental QoL.3,5
**With the EQ-5D-5L index, numerical improvements were observed at Week 26, and significant improvements were observed at Week 52 (p=0.009) in the TAVNEOS®-based regimen vs GC-based regimen.5
††The 95% confidence interval of the differences between the TAVNEOS®-based regimen and GC-based regimen groups does not include 0.3
1. Jayne D, et al. N Engl J Med 2021;384(7):599–609. 2. EMA. First-in-class medicine recommended for treatment of rare blood vessel inflammation. Nov. 2021. https://www.ema.europa.eu/en/news/first-class-medicine-recommended-treatment-rare-blood-vessel-inflammation. Last access: October 2023. 3. Jayne D, et al. N Engl J Med 2021;384(7):599–609. [Supp Appendix]. 4. Stone J, et al. Semin Arthritis Rheum 2022;55:152010. 5. Strand V, et al. Lancet Rheumatol 2023;5:e451–60. 6. Cortazar F, et al. Kidney Int Rep 2023;8(4):860–70. 7. McDowell P, et al. J Allergy Clin Immunol Pract 2021;9(1):365–72. 8. Stone JH, et al. N Engl J Med 2010;363(3):221–32. 9. Walsh M, et al. N Engl J Med 2020;382(7):622–31. 10. Charles P, et al. Ann Intern Med 2020;173(3):179–87. 11. TAVNEOS® Fachinformation, www.swissmedicinfo.ch.
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