The company designed it to interfere with the damaging inflammatory response in autoimmune diseases.
How Avacopan works
ANCA vasculitis affects small blood vessels in many organs. Autoimmune diseases like ANCA vasculitis trigger inflammation, which damages tissue. Avacopan interferes with the inflammatory response by blocking the protein C5a.
C5a is a member of the complement system, a family of proteins that plays an important role in immune response. Complement proteins help recruit white blood cells to areas of infection or injury, to defend the body and promote healing. But in autoimmune diseases, white blood cells are recruited to healthy tissue, where they build up and cause damage.
It blocks the effects of C5a by targeting its receptor, C5aR. Blocking C5aR interferes with messages to white blood cells, so fewer are attracted to inflammation sites.
Avacopan in clinical trials
It has been tested in two Phase 2 clinical trials, CLEAR and CLASSIC. A Phase 3 trial is under way.
The goal of the CLEAR trial (NCT01363388) was to see whether Avacopan would allow people with ANCA vasculitis to use a smaller dose of steroids to control their disease. People with ANCA vasculitis may be on high doses of steroids, which decrease inflammation but can have serious side effects. In addition, steroids also suppress healthy immune response, leaving patients vulnerable to infections.
Researchers in the CLEAR trial randomized 67 patients to receive one of three treatment regimens over 12 weeks. One was a high dose of the corticosteroid prednisone plus a placebo. Another was Avacopan plus a reduced dose of prednisone. And the third was Avacopan without prednisone.
The research team measured its effectiveness by how much it reduced patients’ vasculitis activity score.
Results of the CLEAR trial, published in the Journal of the American Society of Nephrology in April 2017, showed that Avacopan without prednisone was as effective as a standard therapy that includes prednisone.
The main goal of the CLASSIC trial (NCT02222155) was to test the safety of adding Avacopan to the standard-of-care regimen used to treat ANCA vasculitis. That regimen includes prednisone plus either cyclophosphamide or Rituxan.
Some of CLASSIC’s 42 patients received Avacopan and the standard-of-care regimen. The control group received only the standard regimen. ChemoCyntryx reported that a combination of Avacopan and the standard regimen was safe.
The Phase 3 as ADVOCATE trial (NCT02994927) will include about 300 patients, who will take Avacopan for 12 months. Researchers will look at how quickly Avacopan works and whether it is able to prevent the disease from recurring, at 26 and 52 weeks. The trial is recruiting participants.
The U.S. Food and Drug Administration (FDA) granted Avacopan orphan drug status, a designation that helps speed up the approval process for drugs being developed to treat rare diseases.
The European Medicines Agency has added Avacopan to the list of therapies that are part of its priority medicines, or PRIME, initiative. The initiative is aimed at accelerating regulatory approval of therapies addressing unmet medical needs.
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