Drugs

FDA Questions Single Trial Adequacy for Avacopan

FDA reviewers are questioning the adequacy of a single Phase 3 trial submitted to support a ChemoCentryx NDA for avacopan, an oral small molecule C5a receptor inhibitor indicated for treating adult patients with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV).

In a briefing document for a 5/6 advisory committee meeting, the reviewers said there are “substantial uncertainties around the Phase 3 study design and results, raising questions about the adequacy of this single trial to inform the benefit-risk assessment.” While the study demonstrated avacopan’s non-inferiority to a pre-specified prednisone taper at Weeks 26 and 52 with both arms receiving background therapy and glucocorticoids, FDA said that a “non-inferiority comparison would not be sufficient to show that avacopan can replace glucocorticoids as it would be difficult to distinguish whether avacopan is effective or whether the induction treatment with rituximab/cyclophosphamide was the primary driver of the efficacy in both treatment arms.”

FDA reviewers also raised concerns about the trial’s ability to “adequately justify a margin as the benefit of glucocorticoids when administered with rituximab or cyclophosphamide induction therapy...The utility of a non-inferiority comparison is dependent on knowing that the active control had its expected effect in the non-inferiority study. However, the applicant has not provided adequate data or information that would isolate the effect of prednisone to inform the margin of the non-inferiority comparison in this study. Furthermore, non-protocol-specified glucocorticoids were used to control disease activity which resulted in glucocorticoid use in both treatment arms. Thus, the assessment of non-inferiority is a comparison of avacopan and lower dose glucocorticoids to higher dose glucocorticoids.”

Additionally, the briefing document continued, data from the clinical pharmacology program has identified avacopan as a CYP3A4 inhibitor “that has the potential to increase exposures to systemic glucocorticoids which are CYP3A4 substrates, raising further questions about the true difference in glucocorticoid exposures and its impact on the non-inferiority comparisons between the two groups, and respectively the proposed role of avacopan as a steroid-sparing agent.”

FDA is seeking input from the advisory committee on whether the application provides substantial evidence of efficacy for the proposed indication and overall benefit-risk considerations in AAV as a rare and serious disease.

Gupta Raises Concerns About Overton’s Independence, Ideology

FDA commissioner nominee Heidi Overton’s responses on vaccines, contraception and abortion medication during her 9/24 Senate confirmation hearing raise concerns that ideology could influence her decision-making if she takes over the agency, MSNBC senior medical analyst Dr. Vin Gupta said Friday. Gupta was particularly critical of Overton’

Overton Confirmation Remains Uncertain After Senate Hearing

FDA commissioner nominee Heidi Overton emerged from her Senate confirmation hearing Thursday (see earlier story) without resolving questions about whether she has enough Republican support to advance — and with a rapidly narrowing window for confirmation before the midterm elections. The Senate Health, Education, Labor and Pensions Committee hearing provided few

FDA Classifies Boston Scientific Imager II Catheter Recall as Class I

FDA has classified Boston Scientific's recall of its Imager II Angiographic Catheters as Class I because a manufacturing problem could cause catheter tips to degrade and detach, potentially resulting in life-threatening complications. The agency announced the Class I classification 9/25, updating an Early Alert it issued

FDA Approves Gazyva for Childhood-Onset Idiopathic Nephrotic Syndrome

FDA has approved Roche’s Gazyva (obinutuzumab) for reducing the risk of relapse in adults and children aged 2 and older with frequently relapsing or steroid-dependent, childhood-onset idiopathic nephrotic syndrome who are in remission. The expanded approval covers the use of the CD20-directed antibody beyond its existing

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Gupta Raises Concerns About Overton’s Independence, Ideology

Overton Confirmation Remains Uncertain After Senate Hearing

FDA Classifies Boston Scientific Imager II Catheter Recall as Class I

FDA Approves Gazyva for Childhood-Onset Idiopathic Nephrotic Syndrome