A Phase 3 clinical trial showed that a new medication that suppresses part of the immune system that causes inflammation was more effective than treatment with glucocorticoids (“steroids” like prednisone) in keeping patients with vasculitis associated with ANCA, a disease that causes the destruction of small blood vessels of the body, in remission for a year. The researchers behind the trial believe that a treatment approach that avoids prednisone use could significantly reduce many of the side effects patients experience. These results were published in the New England Journal of Medicine today.
“This is a completely new class of medication for the treatment of autoimmune disease that delivers beneficial effects without the negatives we see when glucocorticoids like prednisone or other similar drugs are used. , ”said Peter A. Merkel, MD, MPH, co – primary academic examiner of the trial, head of Rheumatology in the Perelman School of Medicine at the University of Pennsylvania and director of the International Vasculitis Clinical Research Consortium. “Importantly, avacopan appears to act quickly so it may prevent disease-related damage in this type of vasculitis.”
ANCA-associated vasculitis is a disease that occurs when the body’s white blood cells invade and destroy the body’s small blood vessels. This can affect many organs throughout the body, including kidneys, lungs, nerves, and other areas. About one in 50,000 people suffer from the disease, and their cause is uncertain. Untreated, it is fatal, but treatment significantly increases the survival of the disease.
Currently, treatment for ANCA-related vasculitis usually involves the use of high doses of a glucocorticoid such as prednisone to prevent inflammation that breaks down blood vessels. But the use of prednisone is associated with many side effects, such as increased risks of infection, diabetes, high blood pressure, weight gain, cataracts, and many other complications.
Looking for solutions that could cut steroids out completely, Merkel worked with her co-primary academic researcher David Jayne, MD, professor of nephrology at Cambridge University , with ChemoCentryx to develop avacopan for ANCA-related vasculitis. The basic concept is that C5a, a protein that acts as a “chemoattractant” for inflammatory cells, including neutrophils, provided a good opportunity to stop ANCA-related vasculitis in its pathways.
“There is strong data from animal models that C5a is directly involved in the as yet undiagnosed cause of ANCA-related vasculitis,” Merkel explained. “These models show that inhibition of C5a at the tissue level has the potential to rapidly stop at least part of the destructive destructive process in this disease.”
To confirm this, the clinical trial (named ADVOCATE) enrolled 331 patients. They were randomized into two groups: the control group, who took prednisone as their level of care; and the test group, which received avacopan. Both groups also received cyclophosphamide (followed by azathioprine) or rituximab, other medications that are common for vasculitis. The depth of the disease at each patient was measured using a standard instrument in vasculitis tests, the Birmingham Vasculitis Activity Score (BVAS), which helped determine who had received relief.
The researchers first measured whether patients achieved relief from vasculitis 26 weeks (half a year) after starting their treatments. Both groups achieved similar levels of relief, with approximately 72 percent of patients with avacopan treatment receiving relief and 70 percent of patients with prednisone treatment. This showed that avacopan performed just as well as prednisone.
However, a year later, the findings showed that avacopan patients were more likely to remain in remission. At that level, 66 percent of the original patients treated with avacopan were in remission, compared with 55 percent of the patients treated with prednisone.
In addition, severe adverse events such as exacerbated vasculitis, severe infections, and also death occurred 33 percent more frequently in the prednisone group than the avacopan group.
Avacopan is currently under review by the U.S. Food and Drug Administration (FDA) for approval as a treatment for ANCA-related vasculitis.
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Other authors of this study include Thomas J. Schall, PhD, and Pirow Bekker, both of ChemoCentryx.
Editor’s note: The ADVOCATE trial was funded by ChemoCentryx, which holds the patent for avacopan. Merkel and Jayne have been paid consultants for the company.
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