FDA Approves ChemoCentryx’s Tavneos in ANCA-Associated Vasculitis

The U.S. Food and Drug Administration approved ChemoCentryx’s Tavneos, an orally administered selective complement 5a receptor inhibitor, as an adjunctive treatment of adult patients with the rare and severe autoimmune disease anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, in combination with standard therapy.

The approval of Tavneos for ANCA-associated vasculitis is for granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), the two main forms of ANCA vasculitis, in combination with standard therapy. It comes after the company filed an amendment to its New Drug Application for Tavneos following talks with the FDA that addressed points raised during the FDA Advisory Committee meeting in May that was split on whether the efficacy and safety data warranted approval.

ANCA-associated vasculitis is a systemic disease in which over-activation of the complement pathway further activates neutrophils, leading to inflammation and destruction of small blood vessels. This results in organ damage and failure, with the kidney as the major target, and is fatal if not treated. Currently, treatment for ANCA-associated vasculitis consists of courses of non-specific immuno-suppressants, combined with the administration of daily steroids for prolonged periods of time, which can be associated with significant clinical risk including death from infection.

Tavneos (avacopan) is a first-in-class, orally administered small molecule that employs a novel, highly targeted mode of action in the treatment of ANCA-associated vasculitis and other complement-driven autoimmune and inflammatory diseases. By precisely blocking the receptor for the pro-inflammatory complement system fragment known as C5a on destructive inflammatory cells, such as blood neutrophils, avacopan arrests the ability of those cells to do damage in response to C5a activation, which is known to be the driver of 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, 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.”

Tavneos 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. The ADVOCATE trial of Tavneos 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 Tavneos 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 percent 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 increase, and paresthesia.

ChemoCentryx is responsible for the discovery and development of Tavneos 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 of the U.S.

Tavneos is also approved for the treatment of microscopic polyangiitis and granulomatosis with polyangiitis in Japan. The regulatory decision in Europe following the European Medicines Agency (EMA) review is expected by the end of 2021.

Author: Rare Daily Staff