On Oct. 8, ChemoCentryx Inc. announced that the U.S. Food & Drug Administration (FDA) has approved avacopan (TAVNEOS), an orally administered selective complement 5a receptor inhibitor, as an adjunctive treatment of adult patients with severe active anti-neutrophil cytoplasmic autoantibody-associated vasculitis (ANCA-associated vasculitis), specifically granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) (the two main forms of ANCA vasculitis), in combination with standard therapy. ANCA-associated vasculitis is a systemic autoimmune disease in which over-activation of the complement system further activates neutrophils, leading to inflammation and eventual destruction of small blood vessels. This results in organ damage and failure, with the kidney as the major target, and is often fatal if not treated.
“We look forward to making TAVNEOS available to clinicians and patients in the next few weeks,” said Thomas J. Schall, PhD, president and chief executive officer of ChemoCentryx.
“I am excited that our work has helped lead to the first-in-a-decade approval of a medicine for ANCA-associated vasculitis. This is an important step forward in the treatment of this disease,” said the trial’s co-primary academic investigator Peter A. Merkel, MD, MPH, the chief of rheumatology at the Perelman School of Medicine at the University of Pennsylvania, director of the international Vasculitis Clinical Research Consortium, and consultant to ChemoCentryx. “Patients will now have access to a new class of medication that provides beneficial effects for the treatment of ANCA-associated vasculitis.”
“The vasculitis community is elated that TAVNEOS is now approved, bringing a much-needed new treatment option to patients living with this devastating disease,” said Joyce Kullman, executive director, Vasculitis Foundation. “There is a significant unmet need in the treatment of ANCA-associated vasculitis, with current therapies often leading to serious, even fatal, side effects and a diminished quality of life. We believe new therapies like TAVNEOS may offer a brighter future for these patients.”
Avacopan is the first FDA approved orally administered inhibitor of the complement C5a receptor. The approval in ANCA-associated vasculitis was supported by the results of the pivotal phase 3 ADVOCATE trial, which were highlighted in the February 2021 edition of The New England Journal of Medicine (NEJM). The ADVOCATE trial of avacopan was a global, randomized, double-blind, active-controlled, double-dummy phase 3 trial of 330 patients with ANCA-associated vasculitis in 20 countries. Eligible study subjects were randomized to receive either rituximab or cyclophosphamide (followed by azathioprine/mycophenolate) and either avacopan or study-supplied oral prednisone. Subjects in both treatment groups could also receive non-protocol glucocorticoids if needed. The study met its primary endpoints of disease remission at 26 weeks and sustained remission at 52 weeks, as assessed by the Birmingham Vasculitis Activity Score, or BVAS. The study demonstrated superiority to a prednisone-based standard of care with respect to sustained remission at 52 weeks. The most common adverse reactions (≥5% of patients and higher in the avacopan group vs. prednisone group) were: nausea, headache, hypertension, diarrhea, vomiting, rash, fatigue, upper abdominal pain, dizziness, blood creatinine increase, and paresthesia.
ChemoCentryx has developed TAVNEOS Connect, a patient support program designed to assist patients who are prescribed avacopan. To learn more about avacopan or TAVNEOS Connect, visit www.TAVNEOS.com.
ChemoCentryx is responsible for the discovery and development of TAVNEOS (avacopan) and owns the commercial rights to the drug in the United States. ChemoCentryx’s Kidney Health Alliance with Vifor Pharma provides Vifor Pharma with exclusive rights to commercialize TAVNEOS in markets outside the U.S.
TAVNEOS (avacopan) is also approved for the treatment of microscopic polyangiitis and granulomatosis with polyangiitis (the two main forms of ANCA-associated vasculitis) in Japan. The regulatory decision in Europe following the European Medicines Agency (EMA) review is expected by the end of 2021.
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.
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 six 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 risk and benefit before administering this drug to a patient with liver disease.
Serious Hypersensitivity Reactions: Cases of angioedema occurred in a clinical trial, including one serious event requiring hospitalization. Discontinue immediately if angioedema occurs and manage accordingly. TAVNEOS must not be re-administered 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 six 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 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 coadministration 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. Monitor for adverse reactions and consider dose reduction of certain sensitive CYP3A4 substrates.
Please see Full Prescribing Information and Medication Guide for TAVNEOS.