After skepticism and tight vote at adcomm, FDA approves ChemoCentryx's rare disease drug
After a tight advisory committee vote back in May that tilted just slightly in favor of approving ChemoCentryx’s avacopan, the FDA has officially cleared the drug to treat a rare and serious disease known as anti-neutrophil cytoplasmic autoantibody (ANCA)-vasculitis.
The approval makes avacopan — now marketed as Tavneos — the first new drug in a decade for ANCA-associated vasculitis, according to trial investigator Peter Merkel.
ANCA-associated vasculitis refers to a group of autoimmune diseases characterized by inflammation and damage to small blood vessels. It’s often caused by ANCAs, self-reactive antibodies that bind to a type of white blood cells called neutrophils and overactivate them.
It’s a potentially fatal condition that’s notoriously expensive to treat. Back in 2019, Rituxan, a current standard of care, made ICER’s list of top price-hike offenders. According to CEO Thomas Schall, Tavneos’ price will fall somewhere between $150,000 to $200,000 per patient per year.
The drug, a small molecule antagonist of the C5a receptor, was approved based on data from the Phase III ADVOCATE trial, which enrolled 331 patients in one of two arms: one group received 30 mg of oral avacopan, while the other received oral prednisone on a tapering schedule. All of the patients received either cyclophosphamide (followed by azathioprine) or rituximab.
Researchers were able to show that Tavneos was non-inferior to the prednisone taper at Week 26 (the primary endpoint), and superior to the taper with respect to sustained remission at the one-year mark.
But those numbers didn’t impress some adcomm members, who raised concerns about relying on the single trial as evidence, the insufficient amount of safety data, and questions on whether the trial was statistically robust enough.
The agency also questioned if the other drugs used in the study may have contributed to the efficacy seen for avacopan.
“In this case, both treatment arms received background therapy in the form of cyclophosphamide or rituximab. The benefit of glucocorticoids on top of cyclophosphamide or rituximab is not well understood,” FDA statistical reviewer Yura Kim said back in May. “As a result, it is difficult to determine if similar remission rates observed on both arms can support a conclusion that avacopan is effective or if similarities can be primarily attributed to both arms receiving rituximab or cyclophosphamide.”
The committee ended up voting 10-8 to recommend approving the drug; 9-9 on whether the efficacy data support approval; and 10-8 that the safety profile of avacopan is adequate enough to support approval.
During the investor call, Schall emphasized that Tavneos is indicated as an adjunctive treatment in combination with standard therapy glucocorticoids, and explained the sources of glucocorticoid exposure in the ADVOCATE trial.
“Additional glucocorticoids were allowed in both groups, both the Tavneos and the prednisone standard of care group, as required for, say for example, premedication for rituximab infusion,” Schall said. “You actually have what I call hitchhiker glucocorticoid coming in with each infusion of rituximab.”
“So of course, that’s one of the main sources of glucocorticoid exposure in ANCA vasculitis therapy, and it was certainly a source in the ADVOCATE trial and a source that simply could not be eliminated,” he added.