Last updated Jan. 24, 2022, by Marisa Wexler, MS
Fact-checked by Inês Martins, PhD
Tavneos (avacopan) is an approved oral therapy by ChemoCentryx for people with severe and active microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA), the two most common forms of ANCA-associated vasculitis (AAV).
It became the first new treatment for AAV patients in over a decade in autumn 2021, with the U.S. Food and Drug Administration approving it as an add-on therapy for these indications in October, about one month after a similar approval decision in Japan.
Tavneos was also approved in the European Union in January 2022 to treat severe and active GPA and MPA.
What is ANCA vasculitis?
ANCA vasculitis is an autoimmune disease in which a type of immune cell called neutrophils become overactive and attack small blood vessels in the body. This causes inflammation and damage.
In normal inflammation, the complement system (a family of proteins that play an important role in the immune response) is activated. This signals immune cells to come to the area where there is an injury or infection. Immune cells defend the body against invasion by infectious agents and promote healing.
In ANCA vasculitis, the complement system can be activated by mistake. This means that immune cells “are called” to areas where there is no injury or infection. The accumulation of inflammatory signals damages the blood vessels and tissues where this occurs.
One important signaling protein of the complement system is C5a. Released by cells in distress, it binds to C5a receptors (C5aR) on immune cells and on cells that line blood vessels. When bound to its receptor, C5a signals to immune cells to come to that site.
How Tavneos works
Tavneos contains a small molecule that binds to C5a, preventing it from binding to its receptor. This reduces the number of immune cells that wrongly rush to sites. In this way, Tavneos works to reduce inflammation and damage to small blood vessels in ANCA vasculitis.
Tavneos in clinical trials
CLEAR sought to determine whether Tavneos would allow people with ANCA vasculitis to lower the dose of steroids they use to control their disease. ANCA vasculitis patients can be on high doses of steroids due to inflammation, but these medications can have serious side effects. Steroids also suppress a healthy immune response, leaving patients vulnerable to infections.
During the trial, researchers randomly assigned 67 patients to one of three treatment regimens over 12 weeks: a high dose of the corticosteroid prednisone plus a placebo, Tavneos plus a lower dose of prednisone, or Tavneos plus a placebo. All also received standard doses of cyclophosphamide or Rituxan (rituximab), other medications commonly used to treat ANCA vasculitis. Researchers measured the effectiveness of Tavneos by assessing changes in the Birmingham vasculitis activity score (BVAS), a measure of vasculitis.
Results published in 2017 showed that Tavneos without prednisone was as effective as a standard therapy that included prednisone.
CLASSIC tested the safety of adding Tavneos to the standard-care regimen for ANCA vasculitis, including prednisone plus either cyclophosphamide or Rituxan. Researchers randomly assigned patients to a high dose of Tavneos plus standard of care, a low dose of Tavneos plus standard care, or to a placebo plus standard care.
The combination of Tavneos and the standard regimen was safe, ChemoCentryx reported.
The Phase 3 ADVOCATE trial randomly assigned 331 people with ANCA vasculitis to either Tavneos or prednisone plus the standard care for 52 weeks. The study’s primary goals were to determine if Tavneos was at least as good as prednisone at inducing remission at 26 weeks, and superior to prednisone at maintaining that remission at 52 weeks (as determined by changes in BVAS from the study’s start to week 26 and week 52).
This study met both of its primary goals. Among Tavneos-treated patients, 72.3% achieved remission at 26 weeks, as did 70.1% of those on prednisone. Sustained remission at 52 weeks occurred in 65.7% of the Tavneos-treated group and 54.9% in the control group, which was a significant improvement.
Additional benefits in patients given Tavneos included a reduction in glucocorticoid-related toxicity, significantly better kidney function in those with kidney disease, and improvements in health-related quality of life. Researchers reported fewer serious side effects in the Tavneos group (42%) than in the prednisone group (45%). Most adverse events were related to ANCA vasculitis and were similar to rates in previous trials.
Tavneos is being distributed in the U.S. by rare disease pharmacy PANTHERx.
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