Shares in ChemoCentryx slumped as much as 61.7% on Friday, a day after an FDA advisory panel appeared split on the company's experimental autoimmune drug avacopan, but ultimately voted 10-8 that its benefit-risk profile supports approval for adults with antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis. The advisory panel followed a critical assessment by FDA staff that had questioned the rationale behind some clinical data for the orally-administered complement C5a receptor inhibitor.
Aside from the question on the drug's benefit-risk profile, the advisory committee voted on two other questions. They were split 9-9 on whether the efficacy data support approval of avacopan for ANCA-associated vasculitis patients, and voted 10-8 that the drug's safety profile is adequate to warrant an FDA nod. All three questions referred to the granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) forms of the disease.
ChemoCentryx's marketing application included data from the Phase III ADVOCATE trial of 331 patients who were randomised to receive avacopan or prednisone, both on top of treatment with rituximab or cyclophosphamide/azathioprine. Avacopan demonstrated statistical superiority in sustaining remission at 52 weeks compared to prednisone, according to findings published in the NEJM earlier this year. The drug was also associated with greater improvement in kidney function and significantly lowered glucocorticoid toxicity, compared with prednisone.
However, members of the FDA advisory committee expressed concern about how ChemoCentryx designed the study, with some suggesting it would need to do additional testing for liver toxicity, SVB Leerink analyst Joseph Schwartz said. They also raised concerns about the random use of glucocorticoids in both groups of patients, noting that while glucocorticoids are part of the usual treatment for ANCA-associated vasculitis, they were not officially designated in the ADVOCATE study. "The panelists and the agency seemed to agree that the use of non-study supplied glucocorticoids makes it challenging to interpret the [effectiveness] results, muddying the comparison between the two [groups]," Schwartz said.
Still, Raymond James analyst Steven Seedhouse predicts the FDA will ultimately greenlight avacopan by the July 7 target date. Further, he added "we're actually not changing our…avacopan estimates [of $1.9 billion in peak unadjusted US sales], only our probability of [approval] success," which he now puts at 50%, down from 100% previously. "We're calling this a pure coin flip between now and July 7," Seedhouse said.
However, other analysts are more skeptical about the prospects for ChemoCentryx's drug, with Stifel's Dae Gon Ha saying "we are now moving to the sidelines," while Edward White of H.C. Wainwright called the mixed FDA panel opinion a negative for potential approval and a "significant negative" for the stock. At SVB Leerink, Schwartz said "we now lack conviction in a positive FDA decision, since it seems likely the agency will take a harsher stance than the panel."
ChemoCentryx is also developing avacopan, formerly CCX168, for the treatment of patients with C3 glomerulopathy (C3G) and hidradenitis suppurativa. The FDA has granted avacopan orphan drug designations for ANCA-associated vasculitis and C3G, while the European Commission has done the same with the GPA and MPA forms of the disease, and for C3G as well. ChemoCentryx owns commercial rights to avacopan in the US, while Vifor Pharma has exclusive rights to commercialise the drug in markets outside of the US.
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