5613423 TREATMENT OF ERYTHROID PRECURSOR CELLS FROM β-THALASSEMIC PATIENTS WITH ISOXAZOLE DERIVATIVES: POTENT INDUCTION OF FETAL HEMOGLOBIN (2023)

7:S1 17 (HU).Voxelotor, a first-in-class oral treatment, inhibits sickle hemoglobin polymerization, the molecular basis of red blood cell sickling.Voxelotor is approved in the United States for the treatment of SCD in patients aged 4 years and in the European Union, Great Britain, United Arab Emirates, Kuwait, and Oman for patients aged 12 years.Voxelotor has been provided to eligible patients with SCD in the United Kingdom (UK) through a Medicines and Healthcare Products Regulatory Agency -approved Early Access to Medicines Scheme (EAMS) and through a company Named Patient Program (NPP), both of which allow patients to receive new, unlicensed medicines when there is a clear unmet need.Aims: To describe the UK patient population participating in the voxelotor EAMS and NPP for the treatment of hemolytic anemia due to SCD.Methods: Patients aged 12 years with hemoglobin (Hb) 10.5 g/dL received voxelotor.The EAMS permitted patients to receive a stable dose of HU for 3 months prior to starting voxelotor, whereas NPP allowed patients who were ineligible or intolerant to HU, had a poor/ no response to HU, or had stopped taking HU.Data on demographics, comorbidities, concomitant medications (including blood transfusions), adverse events, markers of hemolysis, vaso-occlusive crises (VOCs) requiring treatment and/or hospitalization, and discontinuation of therapy were collected.Results: As of August 22, 2022, 90 patients (61 in the EAMS and 29 in the NPP) were enrolled.Overall, the mean age (range) was 37.82 years (12-66), 53.33% (48/90) were female, 75.56% (68/90) were of African or Afro-Caribbean origin, and the most common genotype was HbSS (97.78%, 88/90) (Table ).At baseline, mean (SD) [range] Hb was 7.54 (1.43) [4.6-10.8]g/dL.At baseline, 45.9% (28/61) of patients were taking HU, and 18.03% (11/61) had discontinued previous use of HU; 1.64% (1/61) had been treated with crizanlizumab, and 50.82% (31/61) reported having simple and/or exchange transfusions.In the 12 months before initiating voxelotor, the mean (SD) number of VOCs requiring hospitalization was 0.84 (1.52).Other reasons for hospitalization included admission for VOC (24.59%, 15/61), acute chest syndrome (4.92%, 3/61), transfusion (9.84%, 6/61), hyperhemolysis (3.28%, 2/61), and other (9.84%, 6/61).A total of 9.84% (6/61) of patients reported 3 emergency department (ED) admissions, and alloimmunization was reported in 19.67% (12/61) of patients.Summary/Conclusion: The UK EAMS and NPP provide voxelotor to patients with SCD with limited treatment options.Clinical measures, ED visits, and hospital admission rates of patients participating in the voxelotor EAMS and NPP demonstrate the characteristics of patients selected for the early access scheme and highlight the unmet treatment needs among representative patients with SCD in the UK.Baseline hemolytic parameters and Hb levels are critical not only for defining patient eligibility, but as follow-up measures for patients while receiving voxelotor treatment.Data on the impact of voxelotor on clinical outcomes are forthcoming.