The request, in the form of a new drug application (NDA), is based on data from the ADVOCATE Phase 3 trial (NCT02994927) in adult patients. Results showed that avacopan is better than the corticosteroid prednisone at sustaining remission, and its use led to greater improvements in kidney function and in health-related quality of life, with fewer serious adverse events.
Based on these data, ChemoCentryx’s partner Vifor Pharma is planning to file a similar request — in the form of a marketing authorization application — with the European Medicines Agency before the end of this year.
“We have achieved a major landmark for ChemoCentryx with the submission of the NDA for avacopan in ANCA-associated vasculitis following our highly successful Phase 3 ADVOCATE trial,” Thomas J. Schall, PhD, president and CEO of ChemoCentryx, said in a press release.
Several studies indicate that the complement system — a set of more than 30 blood proteins that contribute to the body’s natural immune defenses — plays a major role in the development of AAV. Activation of this part of the immune system also appears to have a role in AAV-associated kidney damage.
Avacopan (CCX168) is an investigational small molecule inhibitor of the C5a protein, one of the most potent pro-inflammatory proteins of the complement system. As such, it is designed to lessen the inflammation and blood vessel damage brought on by this disease.
ADVOCATE assessed the safety and efficacy of avacopan versus prednisone, both given in combination with standard of care, at inducing and maintaining remission in AAV patients.
Top-line trial data showed that the avacopan combination not only increased the proportion of patients achieving remission after 26 weeks, but it was also superior to the prednisone combo at keeping patients in remission at one year — meeting both of the study’s primary goals.
Additionally, patients given avacopan showed significantly lesser evidence of glucocorticoid toxicity, a major side effects of conventional AAV therapy, as well as greater improvements in kidney function and life quality compared with those given prednisone.
Avacopan was also found to have a favorable safety profile, and to cause fewer serious adverse events than prednisone. Those mostly commonly reported were related to underlying AAV manifestations, with a frequency similar to previously published AAV trials.
“There is an urgent need for a non-immunosuppressive, targeted therapy that can achieve and sustain remission in this organ- and life-threatening disease, while reducing the toxicities associated with daily steroid use. Submission of our NDA is a critical step toward addressing this unmet need, as we seek to improve patients’ lives,” Schall said.
The medication has been designated an orphan drug by both the FDA and the European Commission for the treatment of AAV.
ChemoCentryx holds commercial rights to avacopan in the U.S., while Vifor Pharma owns and retains the medication’s commercial rights for nearly all other countries. In Japan, avacopan’s development and commercial rights have been sub-licensed to Kissei Pharmaceutical.