FDA Finally Approves ChemoCentryx's Tavneos for ANCA Vasculitis
The U.S. Food and Drug Administration (FDA) approved ChemoCentryx’s Tavneos (avacopan) as an adjunctive treatment for adults with severe active anti-neutrophil cytoplasmic autoantibody-associated vasculitis (ANCA-associated vasculitis or ANCA vasculitis). Specifically, the approval was for granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), the two primary types of ANCA vasculitis. The drug was approved in combination with standard therapy.
The company initially had a PDUFA date three months earlier, but the agency requested additional information. Once ChemoCentryx complied, the FDA declared the filing of a significant amendment and extended the target action date.
The drug was approved in Japan on September 27 to treat microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). Tavneos is a first-in-class, oral small molecule that blocks the C5aR receptor for the pro-inflammatory complement system fragment known as C5a on destructive inflammatory cells such as blood neutrophils.
ANCA-associated vasculitis is a systemic autoimmune disease. It is caused by over-activation of the complement system, part of the immune system. This further activates neutrophils, causing inflammation and the eventual destruction of small blood vessels. This leads to organ damage and failure. The kidney is the primary target and is often fatal if not treated.
“Today is a momentous day in the history of ChemoCentryx; the culmination of decades of effort aimed at offering new hope to patients with this and other debilitating and deadly diseases,” said Dr. Thomas J. Schall, president and chief executive officer of ChemoCentryx. “We look forward to making Tavneos available to clinicians and patients in the next few weeks.”
Schall added, “We thank the Agency for their collaboration and consideration and we are also immensely grateful to the pioneering scientists, clinicians and patients who believed in the promise of Tavneos and who have worked tirelessly to make it a reality, along with my dedicated and talented colleagues at ChemoCentryx.”
The approval was partially built on data from the pivotal Phase III ADVOCATE trial, which was also published in the February 2021 issue of The New England Journal of Medicine. The study evaluated 330 patients with ANCA-associated vasculitis in 20 countries. Patients were randomized to receive either rituximab or cyclophosphamide followed by azathioprine/mycophenolate and Tavneos or oral prednisone. Participants in both groups were able to take non-protocol glucocorticoids if necessary.
The trial hit its primary endpoints of disease remission at 26 weeks and sustained remission at 52 weeks. It also demonstrated superiority to a prednisone-based standard of care in terms sustained remission. The most common side effects were nausea, headache, hypertension, diarrhea, vomiting, rash, fatigue, upper abdominal pain, dizziness, blood creatinine increase, and paresthesia (burning or prickling sensation).
ChemoCentryx handled the discovery and development of the drug and holds commercial rights to it in the U.S. The company’s Kidney Health Alliance with Vifor Pharma gives Vifor exclusive rights to commercialize it in markets outside the U.S. A regulatory decision is expected in Europe by the end of this year.
“I am excited that our work has helped lead to the first-in-a-decade approval of a medicine for ANCA-associated vasculitis,” said Peter A. Markel, chief of Rheumatology at the Perelman School of Medicine at the University of Pennsylvania, director of the international Vasculitis Clinical Research Consortium, the trial’s co-primary academic investigator, and consultant to ChemoCentryx. “This is an important step forward in the treatment of this disease. Patients will now have access to a new class of medication that provides beneficial effects for the treatment of ANCA-associated vasculitis.”