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BSH 2023 Oral abstracts book BSH23OR01 | Control of hemolysis in paroxysmal nocturnal hemoglobinuria following switching from HighDose Eculizumab to Ravulizumab Dr Morag Griffin, Dr Shreyans Gandhi, Ms Eden Hicks, Dr Deepak Jain, Dr Richard Kelly, Dr Talha Munir, Dr Petra Muus, Dr Masayo Ogawa, Dr Roochi Trikha, Mr Ji Yu, Dr Austin Kulasekararaj 1St James's University Hospital, Leeds, UK, 2King's College Hospital, London, UK, 3Alexion, AstraZeneca Rare Disease, Boston, USA The complement C5 inhibitors eculizumab and ravulizumab are the current standards of care in patients with paroxysmal nocturnal haemoglobinuria (PNH), a rare chronic blood disorder. Ravulizumab provides the same clinical benefit as eculizumab in patients with PNH at a longer dosing interval (every 8 weeks [q8w] vs every 2 weeks [q2w]). Approximately 10%– 15% of patients with PNH who receive the approved, fixed eculizumab dose (900 mg q2w) experience insufficient inhibition of intravascular haemolysis (IVH), characterised by breakthrough haemolysis (BTH) towards the end of the dosing interval. In such patients, increasing the eculizumab dose can be effective. However, currently there are no recommendations or clinical trial data regarding the impact of switching these patients to ravulizumab. Study 401 (NCT04320602) is an ongoing, phase 4, singlearm, multicentre trial designed to investigate the impact of switching treatment from fixed, highdose IV eculizumab (1200 mg q2w) to weightbased IV ravulizumab q8w in adult (≥18 years of age; N = 18) patients with PNH. The primary endpoint is the proportion of patients who experience serum free C5associated BTH (defined as ≥1 new or worsening symptom or sign of IVH with lactate dehydrogenase [LDH] levels ≥2 x upper limit of normal [ULN] and free C5 concentrations ≥0.5 μg/mL). Other endpoints include change in free C5 concentrations and LDH levels over time. This interim analysis describes data up to day 183 of followup. Data for 10/18 enrolled patients (55.6%) were available. From baseline to day 183, no instances of free C5associated BTH were reported, free C5 concentrations remained below 0.5 μg/mL for all patients at all study timepoints, and LDH levels remained ≤1.5 × ULN in all patients. Up to day 183, 7/10 patients (70.0%) reported treatmentemergent adverse events that were mild (n = 3, 30.0%) or moderate (n = 4, 40.0%) in severity. BTH was reported in one patient which was deemed vaccinerelated as two vaccinations were administered the day prior to the event. No elevated free C5 level was detected in the earliest available sample (0.11 μg/ mL, collected four days after the event) and the patient continued ravulizumab treatment. Results of this interim analysis showed that in a sample of ten patients with PNH, switching from highdose IV eculizumab to standard, weightbased IV ravulizumab q8w was well tolerated. Up to day 183, no free C5associated BTH was reported and the safety profile of ravulizumab was considered comparable to previously published studies. BSH23OR02 | Efficacy and safety of biosimilar ABP 959 compared with reference eculizumab in adults with PNH Dr Austin Kulasekararaj, Dr. Francesco Lanza, Dr. Alexandros Arvanitakis, Dr. Saskia Langemeijer, Dr. Satheesh Chonat, Dr. Jean Pan, Dr. Vincent Chow, Dr. Yaneth Saportas, Dr. Haby Henary 1King's College Hospital, London, UK, 2Azienda USL della Romagna, Ravenna, Italy, 3Skånes Universitetssjukhus Malmö, Sweden, 4Radboud Universitair Medisch Centrum, Nijmegen, Holland, 5Emory University and Children's Healthcare of Atlanta, Atlanta, USA, 6Amgen Inc., Thousand Oaks, USA Introduction: ABP 959, a biosimilar to eculizumab reference product (RP), binds to the human complement component 5 protein to inhibit the progression of the complement cascades. Reference eculizumab is approved for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH). Methods: This multicenter, randomised, doubleblind, activecontrolled, 2period crossover study evaluates the clinical similarity of ABP 959 compared with RP in adult patients with PNH. Patients were randomised 1:1 to receive each investigational product (900 mg of ABP 959 or RP IV q14d) in one of two treatment sequences (ABP 959/RP or RP/ ABP 959). Primary efficacy for the crossover comparison was determined by hemolysis, measured by the timeadjusted area under the effect curve (AUEC) of lactate dehydrogenase (LDH) from weeks 13 to 27, 39 to 53, and 65 to 79. The similarity of AUEC between treatment groups was assessed by comparing the 2sided 90% confidence interval (CI) for the geometric mean ratio (GMR) of the timeadjusted AUEC DOI: 10.1111/bjh.18718 © 2023 The Authors. British Journal of Haematology © John Wiley & Sons Ltd