In light of upcoming Phase 3 data, ChemoCentryx and Vifor Fresenius Medical Care Renal Pharma have decided not to pursue the conditional approval of avacopan in Europe for patients with ANCA-associated vasculitis.
Instead, the companies plan to submit a full (unconditional) marketing approval application for the therapy in 2020 with both the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA).
“Since pivotal topline data will be available from our global Phase III ADVOCATE trial later this year, we have decided not to proceed with our limited Phase II-based CMA (conditional marketing authorization) in Europe,” Thomas J. Schall, PhD, president and CEO of ChemoCentryx, said in a press release.
Avacopan is a small molecule that inhibits the complement 5a receptor (C5aR), involved in inflammatory signals of ANCA-associated vasculitis. It was granted orphan drug status by the FDA and EMA, which are expected to support and expedite the development and regulatory approval of the investigational therapy.
In January 2018, EMA said it would review avacopan’s Conditional Marketing Authorization (CMA) as a treatment for ANCA-associated vasculitis patients, based on data from the CLEAR Phase 2 trial (NCT01363388). The trial included 67 patients and showed that treated patients could reduce their use of corticosteroids significantly, which overall led to fewer adverse events and better quality of life.
However, the conditional approval — if granted — would be contingent on additional Phase 3 data confirming the benefits of avacopan in this patient population.
Thus, the company designed a Phase 3 trial, called ADVOCATE (NCT02994927), to compare avacopan versus prednisolone in patients receiving standard care — Rituxan (rituximab) or cyclophosphamide, followed by azathioprine.
The main objective of the ADVOCATE trial is to see if avacopan can put patients into remission. The trial will also look at whether oral avacopan can prevent the disease from returning — something other therapies are unable to do.
Topline results, scheduled to be released by the fourth quarter of 2019, are expected to support a full approval of avacopan.
“We strongly support the decision to focus on a full Market Authorization. We believe this will offer regulators and the companies a much clearer view of the performance of avacopan in the treatment of ANCA-associated vasculitis,” said Stefan Schulze, president of the executive committee, and COO of Vifor Pharma Group.
“Since Phase III ADVOCATE assesses more than 300 ANCA vasculitis patients through 52 weeks of treatment, the imminent comprehensive data set will be much more powerful than those in the CMA application, therefore enabling a more consistent set of filings in Europe and the U.S.,” added Schall.