ChemoCentryx Amends Approval Application for Avacopan

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by Steve Bryson PhD |

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ChemoCentryx has filed an amendment to its application seeking approval of avacopan, an investigational therapy for the treatment of ANCA-associated vasculitis (AAV).

The filing addresses the issues raised by an advisory committee of independent medical experts during a recent meeting with the U.S. Food and Drug Administration (FDA). That panel provided the agency with non-binding recommendations.

At that meeting, the committee voted 10–8 on whether avacopan’s safety profile was adequate to support approval, 9–9 that the therapy’s efficacy data was sufficient to support approval, and 10–8 on whether the benefit-risk profile backed the approval at the suggested dose of 30 mg twice daily.

The FDA indicated that this new filing constituted a major amendment to the application. As a result, a final decision on whether to approve avacopan is now expected by Oct. 7.

“We appreciate the opportunity to put additional data and information before the Agency, information which we believe addresses many of the issues raised at the Advisory Committee meeting,” Thomas Schall, PhD, president and CEO of ChemoCentryx, said in a press release. “We look forward to continuing discussions with the Agency.”

ChemoCentryx’s approval application was based on the ADVOCATE Phase 3 clinical trial (NCT02994927), which evaluated avacopan’s safety and effectiveness in 331 AAV patients in 20 countries.

In people with AAV, part of the immune system known as the complement cascade is overactive, which leads to swelling and damage of small blood vessels, particularly those in the kidneys.

Current AAV treatment consists of regimens of non-specific immunosuppressant medications, such as cyclophosphamide or rituximab, along with daily anti-inflammatory glucocorticoids, which are associated with significant risks of infection. Avacopan is an oral medication designed to block the activity of the complement cascade, preventing the attack on blood vessels.

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ADVOCATE participants were assigned randomly to avacopan or the glucocorticoid prednisone for one year. In both treatment arms, patients also received either cyclophosphamide or rituximab, followed by azathioprine.

The study demonstrated that avacopan was similar to prednisone (non-inferior) at promoting clinical remission at week 26, and superior to the steroid at sustaining that remission at week 52, meeting its primary outcome goals.

The advisory committee was concerned that non-inferiority of avacopan was not enough to show that it can replace glucocorticoids, particularly because most patients received glucocorticoids outside the study’s protocol. They also raised more questions about actual glucocorticoid exposures given how avacopan can increase exposure to systemic glucocorticoids.

There also were differences between patient subgroups who received cyclophosphamide or rituximab, and in the assessments performed by the study’s overseeing committee and investigators.

At a recent meeting, ChemoCentryx highlighted data from the ADVOCATE trial that avacopan improved kidney function in AAV patients better than steroids, especially among those with advanced kidney disease.

The European Medicines Agency recently agreed to review an application to market avacopan for the treatment of AAV and is expected to make a decision later this year. The Japanese Pharmaceuticals and Medical Device Agency also is reviewing avacopan.