BACKGROUND: The introduction of the bispecific antibody emicizumab-kxwh has driven a paradigm shift in the management of patients with hemophilia A. Emicizumab-kxwh is gradually replacing factor VIII as the treatment of choice for prophylaxis. The requirement to dose emicizumab-kxwh by weight can drive waste when the appropriate combination of various strengths of single-use vials is not considered, whereas inappropriate rounding to full vials can lead to significantly subtherapeutic or supratherapeutic doses. OBJECTIVE: To quantify waste reduction and impact to savings when a clinical program designed to optimize the emicizumab-kxwh dose, frequency, and vial combination is applied at the dispensing specialty pharmacy level. METHODS: The electronic medical records of 360 patients receiving emicizumab-kxwh as maintenance therapy were retrospectively reviewed. Patients were included in the sample if they were male, were aged 18 to 89 years, were inhibitor negative, and had at least 1 new or renewal maintenance prescription in 2021. Three hundred seventy discrete regimens were identified as evaluated per the Regimen Optimization Algorithm - emicizumab-kxwh and included in the final sample. Data collected for each regimen included patient weight, emicizumab-kxwh dose and interval originally prescribed, every 7-day equivalent regimen (to the hundredth of a milligram), vial combination originally ordered, and resulting waste generated. For those regimens failing the algorithm, additional review of pharmacist follow-up and prescriber engagement was performed. When the prescriber adopted a pharmacist recommendation to adjust dose, frequency of administration and/or vial combination, impact to cost was calculated (Medicare Part B 2022 average sale price). RESULTS: 48% (176/370) of reviewed regimens failed specialty pharmacist review because they drove a potentially subtherapeutic or supratherapeutic dose and/or resulted in the use of partial vials that required that the patient discard all emicizumab-kxwh over the prescribed amount with each dose. 112 (64%) of these failed regimens met full criteria for prescriber engagement to recommend a regimen adjustment to dose, frequency of administration, and/or vial combination. These recommendations were adopted in 43% of cases (48/112), resulting in a cumulative savings of 600 mg per dose while also avoiding significant subtherapeutic or supratherapeutic dosing. When factoring in the frequency of administration at the patient level, cumulative annual savings to payers across these 48 accepted recommendations was $1,793,549.76. CONCLUSIONS: These data illustrate that the application of an evidence-based Regimen Optimization Algorithm at the dispensing specialty pharmacy level can reduce waste and drive payer savings while avoiding significant subtherapeutic or supratherapeutic dosing. DISCLOSURES: Accredo, Inc, a specialty pharmacy dispensing emicizumab-kxwh to patients with hemophilia A, employs the authors. Accredo, Inc, is a subsidiary of EverNorth, which also includes Express Scripts, a PBM that adjudicates a portion of emicizumab-kxwh claims.