Avacopan, the complement pathway inhibitor used to treat antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, showed strong effectiveness in an Italian registry study, according to findings published in ACR Open Rheumatology. The data may help settle questions about the drug’s efficacy, though safety concerns remain a focus for regulators. Avacopan gained FDA approval in 2021. Among 32 patients treated across 18 centers for at least one year, all but one achieved clinical remission on avacopan, and 55 percent were able to stop corticosteroids entirely.
Renal Function and Steroid Reduction
Patients in the study saw marked improvements in kidney function. Mean steroid doses fell nearly 80 percent by week 12, dropping from 23 mg of prednisone equivalents per day at baseline to 5 mg per day. Median estimated glomerular filtration rate also rose from 30.5 mL/min/1.73 m2 at the start of treatment to 53.5 mL/min/1.73 m2 at week 52. This increase is clinically significant, though the rate remains below the normal threshold of 60 mL/min/1.73 m2.
The study population included 46 patients identified from Italian records between 2022 and 2024. The average age was 59, and 63 percent were women. Eighteen patients were newly diagnosed with the disease, while the rest had relapsing conditions. About one-third of the group presented with systemic symptoms, and a similar number had kidney involvement when treatment began. Twenty percent demonstrated rapidly progressing glomerulonephritis. Pulmonary and ear-nose-throat symptoms were also common.
Real-World Data in the Wake of Regulatory Issues
The study comes at a time of heightened scrutiny for avacopan. Earlier this year, data from the drug’s main registration trial were re-adjudicated after the study was unblinded, converting a missed endpoint into a success. The New England Journal of Medicine subsequently retracted the paper reporting those findings. The FDA had asked the current manufacturer, Amgen, to withdraw the drug due to new information on liver toxicity and the re-adjudicated data, but Amgen has refused, and the FDA has not issued a formal withdrawal order. European regulators revoked authorization in August.
Researchers argue that independent prospective real-world studies are critical for assessing effectiveness and safety when trial data are under suspicion. While randomized clinical trials provide the basis for regulatory approval, these observational studies describe outcomes and patient-reported quality of life in unselected populations. The current registry did not investigate hepatic effects in detail. Only two patients showed grade 1 liver enzyme elevations that did not interrupt treatment, but long-term safety data remain limited. In avacopan’s phase III trial, 4.2% of patients on the drug had discontinued due to adverse liver effects, and 5.4% had serious hepatic reactions.
Outcomes and Attrition
Clinical remission was defined as a Birmingham Vasculitis Activity Score of zero; any patients in remission who developed any new symptom, and thus a score greater than 0, were considered to have relapsed. Patients were followed for a mean of 61 weeks; for some, follow-up reached 130 weeks.
Among the 46 patients, nine discontinued treatment at some point. Three stopped because symptoms worsened, four due to infections, and two for other reasons. Seven others paused the drug temporarily due to infections or other reasons, such as scheduled surgery. Three patients relapsed, all of whom had a history of relapses before starting avacopan. One of these patients died from a fungal infection after receiving rituximab in an attempt to control symptoms.
At 104 weeks, attrition outcomes were known for 13 patients. Eight were still taking the drug, and five had stopped after week 52 while in remission. All five patients who stopped treatment remained in remission at their last follow-up. Another area of success was getting patients off steroids, which come with their own suite of serious adverse effects when taken for long periods. At week 52, steroid-free remission was achieved by 75% of patients with newly diagnosed disease, although those with relapsing disease did not do so well, with just 40% able to stop the agents altogether. Most patients with extended follow-up continued to receive rituximab, usually every 6 months.
