Request for FDA Approval of Avacopan Likely by Mid-year, ChemoCentryx Says

ChemoCentryx is planning to file a request with the U.S. Food and Drug Administration (FDA) by mid-year seeking approval of avacopan (CCX168) as a treatment for people with ANCA-associated vasculitis (AAV), the company said.

Its new drug application will be supported by results of the Phase 3 ADVOCATE trial (NCT02994927). Topline study data showed avacopan to be superior to standard steroid therapy at sustaining remission in AAV patients, and at improving kidney function and overall quality of life.

Expected costs of the regulatory application and, if approved, avacopan’s commercial launch are supported by a credit line of up to $100 million that the company recently secured.

“We are actively preparing our NDA submission to the FDA following the positive results of the Phase III ADVOCATE trial,” Thomas J. Schall, PhD, president and CEO of ChemoCentryx, said in a press release.

The complement system — a set of more than 30 blood proteins that contribute to the body’s natural immune defenses — is known to play a key role in AAV. Low complement protein levels are also associated with more severe kidney damage in AAV patients.

Current treatments for AAV rely heavily on the use of immunosuppressants. Avacopan works by specifically blocking the C5a protein of the complement system to prevent the activation of inflammatory pathways.

ADVOCATE included 331 AAV patients who received either avacopan or prednisone — one of the most commonly prescribed corticosteroids — in combination with standard care (rituximab or cyclophosphamide, followed by azathioprine) for 52 weeks.

The trial’s goals were the proportion of patients achieving disease remission by week 26 (six months) — and those with sustained remission assessed at one year — as measured by the Birmingham Vasculitis Activity Score (BVAS), and without using glucocorticoid therapy for at least the previous month.

Both objectives were met, with a higher proportion of patients in the avacopan-treated group showing disease remission by week 26 (approximately 72.3%) compared to those on standard glucocorticoid therapy (70.1%).

Disease remission was sustained through 52 weeks in 65.7% of those given avacopan and in 54.9% of patients receiving glucocorticoids.

Patients with renal disease who took avacopan also experienced significant improvements in kidney function, as measured by increases in estimated glomerular filtration rate, and in health-related quality of life — assessed with by EuroQOL-5D-5L.

Avacopan-treated trial patients also showed significantly lower glucocorticoid-related toxicity, a major side effect of long-term AAV standard therapy.

Fewer serious adverse events were reported in the avacopan group (42%) compared to the standard care group (45%). Those most often reported were related to underlying AAV manifestations, and their frequency was similar to previously published AAV trials.

“We at ChemoCentryx are entirely devoted to a different and, we believe, better approach: highly targeted, non-immunosuppressive medicines such as avacopan. Such medicines are entirely unlike the current immune-destroying regimen of high doses of prednisone combined with other immune system dampeners,” Schall said.

Not weakening immune responses can be of particular importance amid the current COVID-19 pandemic.

“A central tenet for our new medicines is ‘do not immune suppress’, and the current crisis provides a stark reminder of exactly why this is so important,” Schall added.