Oral Therapy Avacopan for AAV Now Under Regulatory Review in Europe

The European Medicines Agency (EMA) has agreed to review Vifor Pharma and ChemoCentryx’s application requesting the approval of avacopan to treat granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), the companies announced in a press release.

GPA and MPA are two types of ANCA-associated vasculitis (AAV), a group of autoimmune diseases caused by the production of antibodies that wrongly target the cells lining the blood vessels, promoting vascular inflammation and damage.

A decision is expected in the second half of 2021. Should the European Commission approve avacopan, health authorities in each European Union member state, as well as in Iceland, Liechtenstein, and Norway, will decide whether to bring the therapy into their respective public health programs, where patients can access the treatment at low or no cost.

A similar application also is being reviewed by the U.S. Food and Drug Administration, with a decision due by July 7, 2021.

Avacopan received orphan drug designation in Europe for the treatment of GPA and MPA, and in the U.S. for AAV. It also was granted priority medicine, or PRIME, designation, in Europe for treating AAV.

These designations are meant to speed up the therapy’s development and review by providing regulatory support, financial benefits, and marketing exclusivity upon approval. In Europe, such marketing exclusivity is for 10 years, while in the U.S. that period is seven years.

Previously known as CCX168, avacopan is a first-in-class, orally available small molecule that works by specifically blocking C5a, one of the most potent pro-inflammatory proteins of the complement system.

The complement system is a set of more than 30 blood proteins that contribute to the body’s natural immune defenses and play a key role in AAV. By blocking C5a, avacopan is expected to prevent further inflammation and blood vessel damage.

ChemoCentryx, the therapy’s developer, holds avacopan’s development and commercial rights in the U.S., while Vifor Pharma owns its marketing rights in nearly all other countries. In Japan, avacopan’s development and commercial rights have been sub-licensed to Kissei Pharmaceutical.

If approved, avacopan will become the first orally administered selective C5a inhibitor for the treatment of AAV patients.

The applications were based on data from the ADVOCATE Phase 3 trial (NCT02994927), which evaluated the safety and effectiveness of avacopan against standard glucocorticoid therapy (prednisone) in adults with GPA or MPA.

The trial involved 331 patients who were randomly assigned to receive either avacopan or prednisone, both given alongside standard of care treatment — rituximab or cyclophosphamide, followed by azathioprine — for 52 weeks, or about one year.

The study’s main goals were to assess the proportion of patients achieving disease remission at week 26 (about six months) and sustained remission at one year. Remission was determined by a score of zero in the Birmingham Vasculitis Activity Score and being off glucocorticoid therapy for at least the previous four weeks.

ADVOCATE’s top-line data showed that the trial met its main goals. Avacopan was found to be superior to prednisone both at inducing clinical remission within the first six months of treatment (72.3% vs. 70.1%) and at ensuring patients remained symptom-free more than one year (65.7% vs. 54.9%).

Participants treated with avacopan also showed significantly greater improvements in kidney function and in health-related quality of life compared with those receiving prednisone.

Avacopan was generally well-tolerated and associated with lower glucocorticoid toxicity — a major side effect associated with long-term use of AAV standard therapy — and fewer serious side effects compared with prednisone.

These data highlighted that avacopan can be as or more effective than available standard-of-care glucocorticoid therapies for AAV, but with lower toxicity.