Indication: TAVNEOS (avacopan) is indicated as an adjunctive treatment of adult patients with severe active anti-neutrophil cytoplasmic autoantibody...

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Indication: 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.

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Remission

Primary endpoints

At Week 26, the TAVNEOS® arm was noninferior to the Active Control arm in achieving remission2,*

week-52

At Week 52, the TAVNEOS® arm was superior to the Active Control arm in sustaining remission1,2,†

Efficacy1
Remission data of TAVNEOS® (avacopan) compared to Standard Therapy

TAVNEOS arm = TAVNEOS + rituximab, or cyclophosphamide (followed by azathioprine or mycophenolate mofetil‡).

Active Control arm = prednisone taper + rituximab, or cyclophosphamide (followed by azathioprine or mycophenolate mofetil‡).

91%

of patients in the TAVNEOS® arm who achieved remission at Week 26 remained in remission at Week 52 vs 78% of patients in the Active Control arm2

*

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 26.2

†

Sustained remission was defined as remission at Week 26 and at Week 52 and not taking glucocorticoids for treatment of GPA or MPA within 4 weeks before Week 52, without relapse# between Week 26 and Week 52.1,3

‡

If azathioprine not tolerated.

Prednisone taper: 60 mg/day tapered to 0 over 20 weeks.

#

Relapse was defined as the occurrence of at least 1 major item, at least 3 non-major items, or 1 or 2 non-major items for at least 2 consecutive visits based on BVAS after a BVAS of 0 had been achieved.

Relapse Risk

The TAVNEOS® arm saw a reduced risk of relapse by half compared to the Active Control Arm2

10.1% of patients in the TAVNEOS® arm experienced a relapse, compared with 21% of patients in the Active Control arm2

Risk of relapse data
Efficacy2

Prespecified secondary endpoint not adjusted for multiplicity and subject to post-randomization variable dependence. Results should be interpreted with caution.2

Relapse is defined as the occurrence of one of the following after remission (BVAS of 0) had been achieved:1,2

≥1 major item in the BVAS, or

≥3 minor items in the BVAS, or

1-2 minor items in the BVAS recorded at ≥2 consecutive visits

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.

CI = confidence interval.

Renal Function

The TAVNEOS® arm improved renal function, as measured by eGFR, from baseline compared to the Active Control Arm2

Renal function data
Renal function data
  • 81.2% of patients in the trial had renal involvement based on BVAS prior to treatment2
  • Discontinuation of treatment with TAVNEOS® at Week 52 resulted in the reduction of treatment-induced difference in eGFR3

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; eGFR = estimated glomerular filtration rate.

In a subgroup analysis, patients with stage 4 kidney disease at baseline experienced a least-squares mean change in eGFR improvement:2,4

egfr-improvement
egfr-improvement-sm

Results of a prespecified subgroup analysis in the 100 patients with eGFR <30 and ≥15 mL/min/1.73 m2 at baseline2,4,5

Results of prespecified subgroup analysis in the 100 patients with eGFR <30 mL/min/1.73 m2 and ≥15 mL/min/1.73 m2 at baseline. Results from this exploratory subgroup analysis should be interpreted with caution.2,3,5

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65%

improvement from baseline in the TAVNEOS® arm vs 38% in the Active Control arm2,4

Results of prespecified subgroup analysis in the 100 patients with eGFR <30 mL/min/1.73 m2 and ≥15 mL/min/1.73 m2 at baseline. Results from this exploratory subgroup analysis should be interpreted with caution.2,3,5

Click here to see ADVOCATE data on patients with <br>eGFR 15-20 mL/min/1.73 m<sup>2</sup> at baseline
uACR

Patients in the TAVNEOS® arm saw a decrease in albuminuria by Week 42,3,**

Change in Urinary Albumin-Creatinine Ratio (uACR) Over 52 Weeks (ITT Population)2,3

UACR data
UACR data

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

  • Elevated albuminuria may reflect underlying impairment of kidney function6,7
  • Percent changes from baseline are based on ratios of geometric means of visit over baseline2
  • The uACR analysis was only performed in patients who met BVAS criteria for renal involvement at baseline and who also had a uACR ≥10 mg albumin/g creatinine2
**

Based on percentage change from baseline in uACR in patients with baseline renal involvement and baseline uACR >10 mg/g (52-week study period).2,3

BVAS = Birmingham Vasculitis Activity Score; ITT = intent to treat; LSM = least squares mean; SEM = standard error of the mean.

Click here to see ADVOCATE data on patients with ENT and/or respiratory involvement at baseline
Quality of Life

Patients in the TAVNEOS® arm experienced improved quality of life3

Patients in the TAVNEOS® arm reported greater improvement across physical and mental health-related quality-of-life metrics at Weeks 26 and 52 compared to patients in the Active Control arm3,††

Physical measures

Greater Improvement Seen in the Physical Component Score of the SF-36 (V2) in Patients in the TAVNEOS® Arm8,‡‡

physical-graph
physical-graph-sm
Mental measures

Greater Improvement Seen in the Mental Component Score of the SF-36 (V2) in Patients in the TAVNEOS® Arm8,‡‡

mental-graph
mental-graph-sm

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).3

¶¶

Role-Physical is one of the eight SF-36 domains. It assesses the limitations in routine activities because of physical health capabilities.9

##

Role-Emotional is one of the eight SF-36 domains. It assesses the limitations on routine activities because of emotional factors.9

GPA = granulomatosis with polyangiitis; MPA = microscopic polyangiitis.

Glucocorticoid Exposure

Patients in the TAVNEOS® arm experienced a reduction in glucocorticoid exposure

Total glucocorticoid dose decreased for patients in the TAVNEOS® arm by 10,§§

down-arrow-81
TAVNEOS® arm = 600 mg;
Active Control arm = 3097.5 mg
down-arrow-56
TAVNEOS® arm = 1675.5 mg;
Active Control arm = 3846.9 mg
  • Glucocorticoids were allowed as pre-medication for rituximab to reduce hypersensitivity reactions, taper after glucocorticoids given during the screening period, treatment of persistent vasculitis, worsening of vasculitis, or relapses, as well as for non-vasculitis reasons, such as adrenal insufficiency1
    • The incidence of this non-study-supplied glucocorticoid exposure was balanced between both arms4
  • Results are descriptive

§§ Prednisone equivalent dose per patient.

EULAR guidelines recommend initiating RTX or CYC in combination with glucocorticoids or avacopan for the induction of remission in patients with active GPA/MPA with organ- or life-threatening manifestations. Avacopan may be considered as part of a strategy to reduce exposure to glucocorticoids substantially.1,11

§§ Prednisone equivalent dose per patient.

EULAR = European Alliance of Associations for Rheumatology; RTX = rituximab; CYC = cyclophosphamide.

Explore safety and tolerability data

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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. Obtain liver test panel before initiating TAVNEOS, every 4 weeks after start of therapy for 6 months and as clinically indicated thereafter. Monitor patients closely for hepatic adverse reactions, and consider pausing or discontinuing treatment as clinically indicated (refer to section 5.1 of the Prescribing Information). 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.

Adverse Reactions

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.

Drug Interactions

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 coadministering 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.

INDICATION

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.

References: 1. Sed ut perspiciatis unde omnis iste natus error sit voluptatem accusantium doloremque laudantium, totam rem aperiam, eaque ipsa quae ab illo inventore veritatis et quasi architecto beatae vitae dicta sunt explicabo. Nemo enim ipsam voluptatem quia voluptas sit aspernatur aut odit aut fugit, sed quia consequuntur magni dolores eos qui ratione voluptatem sequi nesciunt. Neque porro quisquam est, qui dolorem ipsum quia dolor.
References: 1. TAVNEOS [package insert]. Cincinnati, OH: Amgen Inc. 2. Data on file, Amgen; Clinical Study Report [92070]; 2020. 3. Jayne DRW, Merkel PA, Schall TJ, Bekker P; ADVOCATE Study Group. N Engl J Med. 2021;384(7):599-609. 4. Terrier B, Pagnoux C, Perrodeau E, et al; French Vasculitis Study Group. Ann Rheum Dis. 2018;77(8):1151-1157. 5. Data on file, Amgen; Study Supplied [91955]; 2021. 6. Chung SA, Langford CA, Maz M, et al. Arthritis Rheumatol. 2021;73(8):1366-1383. 7. Mukhtyar C, Lee R, Brown D, et al. Ann Rheum Dis. 2009;68(12):1827-1832.
References: 1. Chung SA, Langford CA, Maz M, et al. Arthritis Rheumatol. 2021;73(8):1366-1383. 2. Neumann I. Rheumatology (Oxford). 2020;59(Suppl 3):iii60-iii67. 3. Data on file, Amgen. Clinical Study Report [92070];2020. 4. King C, Druce KL, Nightingale P, et al. Rheumatol Adv Pract. 2021;5(3):rkab018. 5. Jain K, Jawa P, Derebail VK, et al. Kidney360. 2021;2(4):763-770. 6. Kitching AR, Anders H-J, Basu N, et al. Nat Rev Dis Primers. 2020;6(1):71. 7. Yates M, Watts R. Clin Med (Lond). 2017;17(1):60-64. 8. Robson J, Doll H, Suppiah R, et al. Rheumatology (Oxford). 2015;54(3):471-481. 9. Geetha D, Jefferson JA. Am J Kidney Dis. 2020;75(1):124-137. 10. Supplement to: Walsh M, Merkel PA, Peh C-A, et al; PEXIVAS Investigators. N Engl J Med. 2020;382(7):622-631. 11. Terrier B, Pagnoux C, Perrodeau E, et al. Ann Rheum Dis. 2018;77(8):1151-1157. 12. Guillevin L, Pagnoux C, Karras A, et al. N Engl J Med. 2014;371(19):1771-1780. 13. Data on file, Amgen. Harris Poll [91973]; 2022. 14. Robson JC, Dawson J, Cronholm PF, et al. Patient Relat Outcome Meas. 2018;9:17-34. 15. Jayne DRW, Merkel PA, Schall TJ, Bekker P; ADVOCATE Study Group. N Engl J Med. 2021;384(7):599-609.
References: 1. TAVNEOS [package insert]. Cincinnati, OH: Amgen Inc. 2. Jayne DRW, Merkel PA, Schall TJ, Bekker P; ADVOCATE Study Group. N Engl J Med. 2021;384(7):599-609. 3. Data on file, Amgen. Clinical Study Report [92070]; 2020. 4. Supplement to: Jayne DRW, Merkel PA, Schall TJ, Bekker P; ADVOCATE Study Group. N Engl J Med. 2021;384(7):599-609. 5. Data on file, Amgen. [92252]; 2020. 6. Kaplan-Pavlovčič S, Cerk K, Kveder R, et al. Nephrol Dial Transplant. 2003;18(suppl 5):v5-v7. 7. Stangou M, Asimaki A, Bamichas G, et al. J Nephrol. 2005;18(1):35-44. 8. Data on file, Amgen. [92757]; 2020. 9. Preedy VR, Watson RR, eds. Handbook of Disease Burdens and Quality of Life Measures. Springer Science+Business Media; 2010. 10. Data on file, Amgen; Study Supplied [91955]; 2021. 11. Hellmich B, Sanchez-Alamo B, Schirmer JH, et al. Ann Rheum Dis. 2023. doi: 10.1136/ard-2022-223764
References: 1. Samman KN, Ross C, Pagnoux C, Makhzoum J-P. Int J Rheumatol. 2021;2021:5534851. 2. TAVNEOS [package insert]. Cincinnati, OH: Amgen Inc. 3. Jayne DRW, Merkel PA, Schall TJ, Bekker P; ADVOCATE Study Group. N Engl J Med. 2021;384(7):599-609.
References: 1. TAVNEOS [package insert]. Cincinnati, OH: Amgen Inc. 2. Chung SA, Langford CA, Maz M, et al. Arthritis Rheumatol. 2021;73(8):1366-1383.
References: 1. TAVNEOS [package insert]. Cincinnati, OH: Amgen Inc. 2. Chung SA, Langford CA, Maz M, et al. Arthritis Rheumatol. 2021;73(8):1366-1383.
References: 1. TAVNEOS [package insert]. Cincinnati, OH: Amgen Inc. 2. Chung SA, Langford CA, Maz M, et al. Arthritis Rheumatol. 2021;73(8):1366-1383.
References: 1. TAVNEOS [package insert]. Cincinnati, OH: Amgen Inc. 2. Data on file, Amgen; Clinical Study Report [92070]; 2020. 3. Khan MM, Molony DA. Ann Intern Med. 2021;174(7):JC79. 4. Chen M, Jayne DRW, Zhao M-H. Nat Rev Nephrol. 2017;13(6):359-367. 5. Kitching AR, Anders H-J, Basu N, et al. Nat Rev Dis Primers. 2020;6(1):71. 6. Al-Hussain T, Hussein MH, Conca W, Al Mana H, Akhtar M. Adv Anat Pathol. 2017;24(4):226-234. 7. Jennette JC, Nachman PH. Clin J Am Soc Nephrol. 2017;12(10):1680-1691. 8. Shochet L, Holdsworth S, Kitching AR. Front Immunol. 2020;11:525. 9. Jones RB, Ferraro AJ, Chaudhry AN, et al. Arthritis Rheum. 2009;60(7):2156-2168. 10. Winkelstein A. Blood. 1973;41(2):273-284. 11. Eickenberg S, Mickholz E, Jung E, et al. Arthritis Res Ther. 2012;14(3):R110. 12. Ogino MH, Prasanna T. In: StatPearls [Internet]. StatPearls Publishing; 2023. Accessed October 3, 2023. https://www.ncbi.nlm.nih.gov/books/NBK553087/ 13. Mohammadi O, Kassim TA. In: StatPearls [Internet]. StatPearls Publishing; 2023. 14. Anders H-J, Nakazawa D. CJASN. 2021;16:1581-1583.
References: 1. Smith RM, Jones RB, Jayne DRW. Arthritis Res Ther. 2012;14(2):210. 2. Berti A, Dejaco C. Best Pract Res Clin Rheumatol. 2018;32(2):271-294. 3. Berden A, Göçeroğlu A, Jayne D, et al. BMJ. 2012;344:e26. 4. Jennette JC, Falk RJ, Bacon PA, et al. Arthritis Rheum. 2013;65(1):1-11. 5. Mukhtyar CB. General presentation of the vasculitides. In: Watts RA, Scott DGI, eds. Vasculitis in Clinical Practice. Springer; 2010:13-19. 6. Terrier B, Darbon R, Durel C-A, et al. Orphanet J Rare Dis. 2020;15(suppl2):351. 7. Chung SA, Langford CA, Maz M, et al. Arthritis Rheumatol. 2021;73(8):1366-1383. 8. Lamprecht P, Kerstein A, Klapa S, et al. Front Immunol. 2018;9:680. 9. Al-Hussain T, Hussein MH, Conca W, et al. Adv Anat Pathol. 2017;24(4):226-234. 10. Qasim A, et al. In: StatPearls [Internet]. StatPearls Publishing; 2023. Accessed March 31, 2023. https://www.ncbi.nlm.nih.gov/books/NBK554372/ 11. Hunter RW, Welsh N, Farrah TE, et al. BMJ. 2020;369:m1070. 12. Chen M, Jayne DRW, Zhao M-H. Nat Rev Nephrol. 2017;13(6):359-367. 13. Yates M, Watts R. Clin Med (Lond).2017;17(1):60-64. 14. Syed R, Rehman A, Valecha G, et al. Biomed Res Int. 2015;2015:402826.
References: 1. Lamprecht P, Kerstein A, Klapa S, et al. Front Immunol. 2018;9:680. 2. Chung SA, Langford CA, Maz M, et al. Arthritis Rheumatol. 2021;73(8):1366-1383. 3. Data on file, Amgen. Clinical Study Report [92070];2020. 4. Jayne DRW, Merkel PA, Schall TJ, Bekker P; ADVOCATE Study Group. N Engl J Med. 2021;384(7):599-609. 5. Supplement to: Jayne DRW, Merkel PA, Schall TJ, Bekker P; ADVOCATE Study Group. N Engl J Med. 2021;384(7):599-609. 6. Mukhtyar CB. General presentation of the vasculitides. In: Watts RA, Scott DGI, eds. Vasculitis in Clinical Practice. Springer; 2010:13-19. 7. Geetha D, Jefferson JA. Am J Kidney Dis. 2020;75(1):124-137. 8. Salama AD. Kidney Int Rep. 2020;5(1):7-12. 9. Hellmich B, Sanchez-Alamo B, Schirmer JH, et al. Ann Rheum Dis. 2023. doi: 10.1136/ard-2022-223764 10. Kitching AR, Anders H-J, Basu N, et al. Nat Rev Dis Primers. 2020;6(1):71. 11. Jariwala MP, Laxer RM. Front Pediatr. 2018;6:226. 12. Macarie SS, Kadar A. Rom J Ophthalmol. 2020;64(1):3-7. 13. Palmucci S, Inì C, Cosentino S, et al. Diagnostics (Basel). 2021;11(12):2318. 14. Lionaki S, Skalioti C, Marinaki S, et al. Pauci-immune vasculitides with kidney involvement. In: Mohammed RHA, ed. Vasculitis in Practice: An Update on Special Situations – Clinical and Therapeutic Considerations. InTechOpen; 2018. 15. Yang J, Li M. BMJ. 2022;376:e065658. 16. Kermani TA, Cuthbertson D, Carette S, et al; Vasculitis Clinical Research Consortium. J Rheumatol. 2016;43(6):1078-1084. 17. Merkel PA, Aydin SZ, Boers M, et al. J Rheumatol. 2011;38(7):1480-1486. 18. Mukhtyar C, Lee R, Brown D, et al. Ann Rheum Dis. 2009;68(12):1827-1832. 19. Pagnoux C. Eur J Rheumatol. 2016;3(3):122-133. 20. Data on file, Amgen. LabCorp Sample [93232]; 2022. 21. Zagelbaum N, Shamim Z, Gilani A, et al. Pulm Crit Care Med. 2016;1(3):1-4.
References: 1. Data on file, Amgen. TAVNEOS Payer Approval Percentage [93621]; 2023. 2. Data on file, Amgen. TAVNEOS Time to First Drug Shipment [93622]; 2023. 3. Data on file, Amgen. Patient and Prescriber Counts [93239]; 2023.
References: 1. Sed ut perspiciatis unde omnis iste natus error sit voluptatem accusantium doloremque laudantium, totam rem aperiam, eaque ipsa quae ab illo inventore veritatis et quasi architecto beatae vitae dicta sunt explicabo. Nemo enim ipsam voluptatem quia voluptas sit aspernatur aut odit aut fugit, sed quia consequuntur magni dolores eos qui ratione voluptatem sequi nesciunt. Neque porro quisquam est, qui dolorem ipsum quia dolor.
Patient cases

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. Obtain liver test panel before initiating TAVNEOS, every 4 weeks after start of therapy for 6 months and as clinically...