What are Severe Active GPA and MPA?

GPA and MPA are part of a rare group of small- to medium-vessel vasculitides called ANCA-associated vasculitis, or AAV^2-4

An AAV diagnosis can be made in part through the clinical assessment of impaired function in one or multiple organs.^5,6

Severe vasculitis is defined by the American College of Rheumatology/Vasculitis Foundation (ACR/VF) guidelines as having life-threatening or organ-threatening manifestations. This is inclusive of multi-organ and localized symptoms⁷
- Approximately 80% to 90% of patients with AAV present with renal or other organ-threatening disease activity⁸
ACR/VF guidelines define “active” as new, persistent, or worsening signs and/or symptoms attributed to GPA or MPA, and not related to prior damage⁷

Severe active GPA and MPA are characterized by neutrophil-induced inflammation and scarring of small- to medium-vessel endothelia⁹

Severe active GPA and MPA characterized by neutrophil-induced inflammation and scarring of small-to-medium vessel endothelia

anca ANCA
c5a C5a
c5a4 C5aR
cytokine-receptor Cytokine receptor
MPO-PR3-antigen MPO/PR3 antigen

The initial injury to vessel walls may result in:⁹
- hemorrhage and
- release of plasma proteins (including coagulation factors) into the vessel walls and adjacent extravascular tissue
Activated coagulation factors produce fibrin that forms at sites of injury which, in time, leads to necrosis⁹
Severe injury to a vessel could manifest in one or more organ systems^7,10,11

C5a = complement fragment 5a; C5aR = C5a receptor; MPO = myeloperoxidase; PR3 = proteinase 3.

Progressive inflammation and vascular injury by neutrophils is perpetuated through a vicious feedback loop that is fueled in part by a complement-mediated pathway¹²

Common Terms

Common terms associated with GPA and MPA
ANCA-associated vasculitis (AAV)	A rare group of necrotizing vasculitides that predominantly affects small-to-medium blood vessels^9,13
Granulomatosis with polyangiitis (GPA)	A subtype of AAV, previously called “Wegener’s granulomatosis,” that features necrotizing granulomatous inflammation and is commonly associated with PR3-ANCA^9,13
Microscopic polyangiitis (MPA)	Another subtype of AAV where granulomatous inflammation is absent and is commonly associated with MPO-ANCA^9,13
Pauci-immune crescentic glomerulonephritis (PICGN)	A form of rapidly progressing glomerulonephritis (RPGN) is one of the common manifestations of GPA and MPA that can lead to renal failure¹⁴

ACR = American College of Rheumatology; ANCA = anti-neutrophil cytoplasmic antibody; GPA = granulomatosis with polyangiitis; MPA = microscopic polyangiitis; MPO-ANCA = myeloperoxidase anti-neutrophil cytoplasmic antibody; PR3-ANCA = proteinase 3 anti-neutrophil cytoplasmic antibody.

See why disease burden may remain high for adult patients with severe active GPA or MPA

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. 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.

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 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.

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/medwatchor calling 1-800-332-1088.

ANCA-associated vasculitis (GPA and MPA) is a group of chronic and progressive autoimmune diseases that affect vasculature throughout the body1

GPA and MPA are part of a rare group of small- to medium-vessel vasculitides called ANCA-associated vasculitis, or AAV2-4

Severe active GPA and MPA are characterized by neutrophil-induced inflammation and scarring of small- to medium-vessel endothelia9

Progressive inflammation and vascular injury by neutrophils is perpetuated through a vicious feedback loop that is fueled in part by a complement-mediated pathway12

Common terms associated with GPA and MPA