Ab1241 Design of Avacostar: A Real-World Study of Avacopan in Anca-Associated Vasculitis (Aav)

Background: Avacopan, a first-in-class oral C5aR antagonist, was shown to be superior to a prednisone taper in sustaining remission, and was associated with improved estimated glomerular filtration rate after 12 months in patients with severe active granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) 1. Avacopan was approved for the treatment of adult patients with severe active GPA and MPA in combination with rituximab or cyclophosphamide by the European Commission in January 2022. The assessment of the EU Marketing Authorization Application for avacopan was based on data available from the clinical development program; however, long term data beyond the 12-month pivotal phase 3 ADVOCATE study period is lacking. Objectives: AVACOSTAR is a post-authorization safety study designed to evaluate the incidence of safety events of interest during long-term follow up in a real-world cohort of participants with GPA and MPA treated with avacopan (NCT05897684) in EU. Methods: AVACOSTAR is a non-interventional, multi-national, prospective cohort study that will enroll participants with severe active GPA/MPA into two cohorts: those treated with avacopan, and a second cohort treated with a cyclophosphamide or rituximab-based induction regimen without avacopan. Participants will be followed until the last patient last visit milestone, 4 years after the last participant is enrolled. All decisions on therapeutic or diagnostic procedures, treatments, disease management, timing of visits, or resource utilization will follow the investigator's usual clinical practice (Figure 1). The primary objective of the study is to evaluate the incidence of defined medical events of special interest (MESIs) in both cohorts. Secondary objectives include evaluating adverse events (AEs), AEs leading to discontinuation of therapy, serious adverse events, adverse drug reactions, serious adverse drug reactions, selected laboratory abnormalities, disease flares, organ damage, and patterns of immunosuppression and glucocorticoid use. Results: The study has been approved in UK and Germany and plans to enroll 500 participants, 250 in each arm, the first of which enrolled in September 2023. Conclusion: The AVACOSTAR study will be the largest real world evidence study conducted to date that evaluates long-term safety of novel therapeutics in GPA/MPA and is expected to yield important insights on the use of avacopan in GPA/MPA in a real-world setting, including continuation beyond 12 months. REFERENCES: 1 Jayne DRW et al. N Engl J Med. 2021;384:599-609. Acknowledgements: NIL. Disclosure of Interests: David R. W. Jayne Lecture fees: Amgen, GSK, CSL Vifor, Stocks: Alentis, Aurinia, Consultancy: Alentis, Amgen, AstraZeneca, Aurinia, Boehringer, Chinook, GSK, Novartis, Otsuka, Roche/Genentech, Takeda, CSL Vifor, Research grants: GSK, Rocher/Genentech, CSL Vifor, Raashid Luqmani Lecture fees: GSK, CSL Vifor, Consulting: GSK, Roche, CSL Vifor Advisory Boards: GSK, Research grants: BMS, Celgene, CSL Vifor, Benjamin Terrier Lecture fees: CSL Vifor, Novartis, AstraZeneca, GSK, Consulting: Boehringer Ingelheim, CSL Vifor, Novartis, AstraZeneca, GSK, Achim Obergfell Stocks: Vifor, Employee: CSL Vifor, Charlotte Pollet Stocks: CSL Vifor, Medtronic Inc., Employee: CSL Vifor, Monica Balcells Stocks: Amgen, CSL Vifor, Employee: CSL Vifor, Marie Boff CSL Vifor, Bernhard Hellmich Lecture fees: Abbvie, Amgen, Boehringer, Chugai, CSL, MSD, Vifor, Pfizer, Sanofi, Novartis, Consulting: CSL Vifor, GSK, Hansa, InflaRx, Novartis Advisory Boards: AstraZeneca, Boehringer, CSL, Novartis, Vifor.