BACKGROUND: Hemophilia A (HA) is marked by substantial economic burden, including costs of ongoing treatment, increased monitoring, bleed events, and other health care utilization associated with managing the disease and comorbidities related to the disease. Gene therapies and other anticipated breakthrough treatments hold potential to substantially offset long-term traditional factor VIII (FVIII) prophylaxis in specific populations. Fragmentation of the US insurance system, however, may impact payers' approaches to coverage of new treatments, given concerns about patients "switching" insurance and the payer's ability to offset costs over time. OBJECTIVE: To assess insurance coverage and switching across payers among people with severe HA (SHA) using real-world data. METHODS: Adult men with SHA (FVIII measuring < 1%) in the American Thrombosis and Hemostasis Network dataset between January 2013 and September 2019 were identified. Patients' primary insurance category (ie, commercial, Medicaid, Medicare) and insurance switching over time were described. Outcomes included distribution of current primary insurance coverage by category and mean years of coverage per payer for commercially insured patients, including those with 2 or more commercial payers, and for those who switched insurance categories (eg, coverage by a commercial payer and government payer). RESULTS: Among the cohort of patients with SHA (N = 3,677), 51.9% had commercial primary insurance and 29.0% had coverage by Medicaid (including state-funded programs). The mean duration of follow-up in the database was 6.3 years for patients with at least 1 year of follow-up. Among patients who had ever been commercially insured, 74.9% had the same commercial payer for the entire follow-up period. The mean time covered by the same commercial insurance was 4.8 years. Only 7.5% of patients switched insurance categories (eg, from commercial to Medicaid). Among those who switched categories, patients averaged 3.9 years of commercial coverage, 4.0 years of Medicaid coverage, and 4.8 years of Medicare coverage during the follow-up period. CONCLUSIONS: Both commercially and government-insured patients with SHA typically maintain continuous coverage for extended periods, with limited switching between payers and insurance categories over time. These findings suggest that should breakthrough treatments be approved, payers would likely be able to realize substantial cost savings associated with avoiding long-term prophylactic therapies during the several years after treatment. DISCLOSURES: This study was funded by BioMarin Pharmaceutical Inc. Hinds, Chen, and Sammon are employees of BioMarin Pharmaceutical Inc. and own stock/stock options. Solari was an employee of BioMarin Pharmaceutical Inc. at the time of the study. Pezalla is CEO of Enlightenment Bioconsult, LLC. He, Cheng, and Recht are, or were at the time of this study, employees of American Thrombosis and Hemostasis Network (ATHN), which has received ATHNdataset licensing and other fees from BioMarin Pharmaceutical Inc. Research funding to Recht's employers has come from Bayer, BioMarin Pharmaceutical Inc., CSL Behring, Genentech, Grifols, Hema Biologics, LFB, Novo Nordisk, Octapharma, Pfizer, Sanofi, Spark, Takeda, and uniQure. Recht has also worked as a consultant for Catalyst Biosciences, CSL Behring, Genentech, Hema Biologics, Kedrion, Novo Nordisk, Pfizer, Sanofi, Takeda, and uniQure; sits on the board of directors of the Foundation for Women and Girls with Blood Disorders and of Partners in Bleeding Disorders; and is an employee of the Oregon Health & Science University. Data from this study were presented as a poster at AMCP Nexus 2021; October 18-21, 2021; Denver, CO.