U.S. FDA approves the first oral complement 5a receptor inhibitor Tavneos

On October 8, 2021, ChemoCentryx announced that the U.S. FDA has approved the oral selective complement 5a (C5a) receptor inhibitor Tavneos (avacopan) to be marketed in combination with standard therapies to assist in the treatment of two main types of antineutrophils Plasma autoantibody (ANCA) related vasculitis: Microscopic polyangiitis (MPA) and granuloma with polyangiitis (GPA). ANCA-associated vasculitis is a rare and serious autoimmune nephropathy with high unmet medical needs. The press release pointed out that this is the first time the FDA has approved an ANCA-related vasculitis drug in ten years, and it is also the first oral complement C5a receptor inhibitor approved by the FDA.

ANCA-related vasculitis is a systemic disease in which excessive activation of the C5a complement pathway further activates neutrophils, leading to inflammation and destruction of small blood vessels, which can cause organ damage and failure. At present, the treatment of ANCA-related vasculitis includes non-specific immunosuppressants (cyclophosphamide or rituximab), combined with daily glucocorticoid long-term administration, which may lead to significant clinical risks, including death due to infection .

Avacopan precisely blocks C5a receptors located on inflammatory cells such as neutrophils to prevent these cells from being activated by C5a and reduce inflammatory damage.

This approval is supported by the positive results of a pivotal Phase 3 trial. Data from 331 patients with polyangiitis and granuloma with polyangiitis showed that according to the Birmingham Vasculitis Activity Score (BVAS), the remission rate of the avacopan group was better than standard treatment at the 52nd week of treatment.

At the 52nd week of treatment, the remission rate of the avacopan group was better than that of the standard treatment

Specifically, at the 52nd week of treatment, 65.7% of patients in the avacopan group observed sustained remission, compared with 54.9% in the control group (non-inferiority P<0.001; superiority P=0.007).

In terms of safety, 37.3% of patients treated with avacopan and 39.0% of patients treated with control drugs had serious adverse events (excluding worsening of vasculitis).