Abstract
BACKGROUND: BAY 81-8973 (Kovaltry®, Bayer) is an unmodified full-length recombinant FVIII indicated for prophylaxis and treatment of bleeds in patients with hemophilia A; BAY 81-8973 was launched in 2016 and has since accumulated 6765 patient-years of exposure. The TAURUS study (NCT02830477) was established to investigate BAY 81-8973 prophylaxis dosing regimens chosen in clinical practice and confirm the established safety and efficacy results from the LEOPOLD clinical trials in a real world setting.
OBJECTIVES: To analyse the proportion of patients on specific BAY 81-8973 prophylaxis regimens, bleeds, and patient-reported outcomes at baseline and most recent follow-up.
METHODS: TAURUS is an international, open label, prospective, non-interventional, single arm study with a target recruitment of 350 previously treated patients with hemophilia A of all ages with moderate or severe hemophilia A (≤ 5% FVIII:C) with ≥ 50 exposure days to any FVIII product who have been switched to prophylaxis with BAY 81-8973. At baseline, physicians document clinical information including age, BMI, severity of hemophilia, number of target joints, prior treatment regimen, bleed history, inhibitor history, and reason for choosing a specific prophylaxis regimen. Patients/caregivers reported bleeds in ongoing patient diaries, and completed questionnaires on treatment satisfaction (HEMOSAT) and adherence (VERITAS-PRO) at baseline and follow-up. A scheduled interim analysis (30% of patients recruited) was conducted with data collected up to 2 July 2018.
RESULTS: At the cut-off, 160 enrolled patients were included in the baseline analysis set, of whom 89 had ≥ 6 months of follow-up data available (median observation period 201 days), 33% of whom had completed one year of the study. Median (range) patient age was 22 (2‒69) years, time since diagnosis was 15 (0.5‒64) years, and most patients (76/89, 85%) had baseline FVIII level of <1%. Treatment assignments are shown in the table. All patients had received pre-study prophylaxis, for a median of 15 years, with 66% of patients using rFVIII-FS as their most recent FVIII treatment prior to BAY 81-8973. Most (91%) had been treated with BAY 81-8973 for <3 months prior to study entry. Pre-study, 72% of patients were treated ≥3 times per week (xW). At baseline, most patients (59%) were assigned treatment ≥3xW (every day, 1%; every other day, 16%; 3xW, 41%). The majority remained on their previous regimen (78% on ≤2xW and 97% on ≥3xW); any changes were mainly a reduction in frequency on BAY 81-8973 vs previous treatment (22%), with only 2% increasing frequency on BAY 81-8973. At last follow up, most patients remained on the same regimen: 60% on ≥3xW (≥ every other day, 17%; 3xW, 42%). Most patients (92%) did not alter their dosing frequency. Of the 8% who changed dosing frequency, the majority (6 patients) changed from ≥3xW to ≤2xW; 1 patient changed from ≤2xW to ≥3xW. The median prescribed weekly dose was 52 IU/kg (64 IU/kg for ≥3xW and 43 IU/kg for ≤2xW) on study, slightly lower than those with previous product: 56 IU/Kg overall, 64 IU/kg for ≥3xW and 50 IU/kg for ≤2xW. Median (Q1; Q3) patient diary-reported annualized joint bleed rates were 1.5 (0.0; 5.3), 1.2 (0.0; 5.3) and 1.4 (0.0; 6.1); for ≤2xW, ≥3xW, and all patients, respectively. HEMO-SAT and VERITAS-PRO data will be presented in the poster. No recruited patients developed inhibitors with BAY 81-8973.
CONCLUSIONS: These real-world data from 89 patients show that the range of dosing options available for BAY 81-8973 allowed the majority of patients to become established quickly on this treatment upon switching. In the few instances where patients changed dosing frequency either upon switching to BAY 81-8973 or once established on treatment, most moved to less frequent treatment. Joint bleeding rates confirm and extend findings from the clinical trials and speak to effective bleeding prophylaxis with BAY 81-8973 in a real-world setting. Therefore, BAY 81-8973 treatment may be successfully individualized according to patient need and disease characteristics.
Disclosures
Wang: Terumo BCT: Other: CPC Clinical Research; CSL Behring: Consultancy; Bayer, Bioverative, Novo Nordisk, Octapharma, Shire, Genentech, Biomarain, Pfizer, CSL Behring, HEMA Biologics, Daiichi Sankyo: Research Funding; Bayer: Consultancy; Bayer, Novo Nordisk, Octapharma, Genentech, HEMA Biologics, Shire, CSL Behring: Honoraria; Novo Nordisk: Consultancy. Maes:Bayer: Honoraria. Rauchensteiner:Bayer: Employment.
Feasibility of Using Real-world Data to Emulate Postapproval Confirmatory Clinical Trials of Therapeutic Agents Granted US Food and Drug Administration Accelerated Approval
