ANCA-Associated Vasculitis (AAV)

Tavneos^® (avacopan) is a medication indicated as an add-on treatment for severe, active antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), specifically the subtypes of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). It is to be used in combination with standard therapy (including glucocorticoids) in adult patients.^1,2

Tavneos was developed by ChemoCentryx and approved by the US Food and Drug Administration (FDA) in October 2021 for this indication of AAV. As a unique complement inhibitor therapy, Tavneos has been shown to provide efficacy in an alternate regimen with a reduced toxicity from traditional therapies.¹ 

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Mechanism of Action

The active substance of Tavneos is avacopan, a small molecule that is orally administered and is a selective inhibitor of the complement C5a receptor, C5aR1.^2,6 Tavneos blocks C5aR1, consequently blocking C5a-mediated neutrophil activation and migration and therefore decreasing the damage caused by these cells.^1,2 

Read more about AAV pathophysiology

Administration

The recommended dosage of Tavneos is 30 mg twice per day, taken with food. Tavneos should be taken on a strict schedule, and any missed doses should be skipped, but never doubled.¹

Adverse Effects

Common adverse reactions to Tavneos are headache, nausea, vomiting, diarrhea, upper abdominal pain, hypertension, dizziness, fatigue, rash, elevated serum creatinine, and paresthesia.

Warnings and Precautions

Patients treated with Tavneos may experience hepatotoxicity, and therefore a liver panel should be obtained before treatment initiation and every 4 weeks during the first 6 months of therapy to evaluate liver function. Tavneos can also lead to reactivation of hepatitis B virus, serious infections that can be life threatening, and hypersensitivity reactions such as angioedema.¹

Read more about AAV complications

Safety and Efficacy in Trials

In preclinical studies using a murine model of ANCA vasculitis, Tavneos was shown to prevent the development of glomerulonephritis induced by antimyeloperoxidase antibodies.³ 

Two phase 2 clinical trials were performed to study the effect of Tavneos on vasculitis.^4,5 The goal of the CLEAR clinical trial (NCT01363388) was to evaluate if treatment with Tavneos would allow a reduction in the dose of systemic corticosteroids administered.⁶ This was a randomized trial that enrolled 67 participants with newly diagnosed or relapsing disease.⁴ Results of the trial showed that Tavneos was not inferior to standard therapy in achieving a treatment response. Treatment response was observed in 86.4% of patients treated with Tavneos and a reduced dose of corticosteroids, 81% of patients receiving Tavneos with no corticosteroid treatment, and 70% of patients in the control group receiving high doses of corticosteroids.⁷ Quality of life was improved, and no safety concerns were reported.⁴

In the CLASSIC (NCT02222155) phase 2 clinical trial, the safety and efficacy of 2 doses of Tavneos, 10 mg and 30 mg per day, were evaluated as adjunction to standard of care (prednisone with Cytoxan® [cyclophosphamide] or Rituxan® [rituximab]) and compared with standard of care alone. The trial enrolled 42 participants with newly diagnosed or relapsed disease.^5,7 The study reported that early achievement of remission within the first month of treatment was superior with 30 mg of Tavneos (20%) when compared to 10 mg of Tavneos (8%) and the standard of care (15%).⁵

A phase 3, double-blind, randomized trial (ADVOCATE, NCT02994927) involving 331 participants led to the approval of Tavneos in 2021.^1,8 The primary objective of this trial was to evaluate the efficacy of the drug in inducing and sustaining remission in patients with ANCA-associated vasculitis when used in combination with Cytoxan followed by Imuran® (azathioprine) or when used in combination with Rituxan.⁸ 

Tavneos was neither inferior nor superior to tapered prednisone in inducing remission of vasculitis at week 26 in the ADVOCATE trial.³ Results also showed that Tavneos was superior to prednisone at week 52 in patients who received concurrent Cytoxan or Rituxan.⁶ At week 26, 72.3% of the patients treated with Tavneos achieved remission, while 70.1% of patients treated with prednisone achieved remission. At week 52, sustained remission occurred in 65.7% of the patients treated with Tavneos, while 54.9% of prednisone-treated patients experienced sustained remission at the same time point.³

Read more about AAV clinical trials

References

1. Tavneos. Prescribing information. ChemoCentryx, Inc; 2021. Accessed February 23, 2023.

2. Tavneos^® (avacopan) recommended by England’s NICE for the treatment of AAV (GPA/MPA). News release. Vifor Fresenius Medical Care Renal Pharma (VFMCRP); August 18, 2022.

3. 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

4. Jayne DRW, Bruchfeld AN, Harper L, et al; CLEAR Study Group. Randomized trial of C5a receptor inhibitor avacopan in ANCA-associated vasculitis. J Am Soc Nephrol. 2017;28(9):2756-2767. doi:10.1681/ASN.2016111179

5. Merkel PA, Niles J, Jimenez R, et al; CLASSIC Investigators. Adjunctive treatment with avacopan, an oral C5a receptor inhibitor, in patients with antineutrophil cytoplasmic antibody-associated vasculitis. ACR Open Rheumatol. 2020;2(11):662-671. doi:10.1002/acr2.11185

6. A study to evaluate the safety and efficacy of CCX168 in subjects with ANCA-associated vasculitis. ClinicalTrials.gov. June 1, 2011. Updated July 27, 2020. Accessed February 23, 2023.

7. Clinical trial to evaluate safety and efficacy of CCX168 in ANCA-associated vasculitis. ClinicalTrials.gov. August 21, 2014. Updated November 16, 2016. Accessed February 23, 2023.

8. A phase 3 clinical trial of CCX168 (avacopan) in patients with ANCA-associated vasculitis (ADVOCATE). ClinicalTrials.gov. December 16, 2016. Updated October 13, 2022. Accessed February 23, 2023.

Reviewed by Kyle Habet, MD, on 2/23/2023.

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Diana Diez Gaspar, PharmD, PhD

Diana earned her PhD and PharmD with distinction in the field of Medicinal and Pharmaceutical Chemistry at the Universidade do Porto. She is an accomplished oncology scientist with 10+ years of experience in developing and managing R&D projects and research staff directed to the development of small proteins fit for medical use.