The European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use has started a review of avacopan (Tavneos, Amgen), a drug authorized in the EU for treating adults with severe, active granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). 

The review comes after emerging information raised questions about how the manufacturer handled the database for the main study supporting the drug’s approval. “Serious questions” have been raised about whether data had been amended and may thus impact the study’s results and reliability, the EMA said. 

The European regulator will now review all available data to see whether the emerging information impacts avacopan’s balance of benefits and risks. The agency will then issue a recommendation to maintain, amend, suspend, or revoke the drug’s marketing authorization in the EU, a decision that will be binding in all EU member states. A decision is expected by March 2026 at the earliest. 

Avacopan was approved for use in the EU in January 2022. There is a high unmet need for medicines to treat GPA and MPA. 

GPA and MPA are rare chronic inflammatory conditions of the blood vessels. GPA affects small blood vessels and tissues in multiple organs, whereas MPA typically affects the kidneys. Symptoms of both conditions include fever, malaise, unexplained weight loss, and muscle pain. 

Left untreated, the average life expectancy of GPA is 5 months, while 90% of those with MPA die within a year. GPA affects 137 per million people in the EU, and MPA affects 35.6 per million.

Avacopan works by blocking receptors for a blood protein called complement 5a to reduce blood vessel inflammation and thus improve symptoms. 

The main study supporting avacopan, known as the ADVOCATE study, included 331 patients with GPA or MPA and compared the effects of high-dose corticosteroids and avacopan, both given alongside standard treatment of rituximab or a regimen consisting of cyclophosphamide followed by azathioprine.

Avacopan was found to be at least as effective as high-dose corticosteroids in inducing remission in patients with GPA or MPA. After 26 weeks, 72% of patients taking avacopan were in complete remission, compared with 70% of those taking corticosteroids at 20 weeks. After a year of treatment, 66% of those on avacopan were still in remission, compared with 55% of those given corticosteroids. 

The most common adverse events among people taking avacopan include nausea, headache, decreased white blood cell count, upper respiratory tract infection, diarrhea, vomiting, and nasopharyngitis. Liver function abnormalities and pneumonia were the most common serious side effects. 

Avacopan is currently taken alongside a rituximab or a cyclophosphamide regimen. The drug is available as a capsule and is taken orally as 30 mg twice daily with meals. Treatment should be started and monitored by clinicians experienced in diagnosing and treating GPA or MPA. 

Annie Lennon is a medical journalist. Her writing appears on Medscape, WebMD, and Medical News Today, among other outlets.