ChemoCentryxs stock price almost halved after the FDA raised concerns with a filing for approval of avacopan. The agency raised multiple concerns with ChemoCentryxs phase 3 clinical trial ahead of an advisory committee meeting to discuss the complement 5a receptor inhibitor this week.
In November 2019, ChemoCentryx reported that avacopan had demonstrated superiority to standard of care at 52 weeks in a form of vasculitis, as well as non-inferiority at 26 weeks. Shares in ChemoCentryx soared after the publication of the top-line data. However, the FDA has now framed the same results in a different light, raising doubts about ChemoCentryxs ability to establish avacopan as a significant product on the strength of its current data.
The FDA reviewers highlighted multiple issues that could affect the interpretability of the data in their briefing document and pre-recorded presentation. The failure to show superiority at Week 26 is part of the problem.
In pre-submission communications, FDA stated that a noninferiority comparison would not be sufficient to show that avacopan can replace glucocorticoids as it would be difficult to establish whether avacopan is effective or whether rituximab/cyclophosphamide was the primary driver of the efficacy in both treatment arms, the agency wrote.
The FDA also raised concerns about the lack of historical clinical trials to support estimates of what glucocorticoids contribute to the effects of combinations based on cyclophosphamide or rituximab. Efforts to compare avacopan to standard of care are further complicated by the fact 86% of subjects on the investigational drug used non-study supplied glucocorticoids over the first 26 weeks of the trial.
ChemoCentryx showed superiority at Week 52, but the FDA cast doubts on the data. In the subgroup of patients on rituximab background induction therapy, the 52-week response rate in patients on avacopan was 15 percentage points higher than the control arm. The delta fell to 3 percentage points in the subgroup on cyclophosphamide. The fact the rituximab group drove the superiority result may be a problem for ChemoCentryx.
The result of the subgroup analysis suggests the possibility that avacopan was efficacious only in the population who did not receive standard-of-care maintenance immunosuppression therapy and may be considered undertreated, raising questions about the adequacy of the comparisons and clinical meaningfulness of the avacopan effect at Week 52, the FDA wrote.
Investors responded to the briefing document by driving ChemoCentryxs share price down 45%. The company will make its case to the outside experts convened by the FDA on Thursday. The FDA wants the experts to vote on whether the safety and efficacy data support the approval of avacopan. 2021 Global Data Point.