All secondary endpoints were met in both Study 301^*† and Study 302^†‡1,2

*Study 301 was a Phase 3 multicentre, randomised, active-controlled, open-label, non-inferiority study to evaluate the efficacy and safety of ULTOMIRIS^® vs SOLIRIS^® (eculizumab) in treatment-naïve adults with a documented diagnosis of PNH. Patients were treated with ULTOMIRIS^® or SOLIRIS^® over a 26-week initial evaluation period. Key inclusion criteria: age ≥18 years, diagnosis of PNH, granulocyte or monocyte clone size ≥5%, and LDH level ≥1.5× ULN at screening. Key exclusion criteria: complement inhibitor-experienced, weight <40 kg. Key inclusion criteria: age ≥18 years, diagnosis of PNH, granulocyte or monocyte clone size ≥5%, and LDH level ≥1.5× ULN at screening. Coprimary endpoints were transfusion avoidance, defined as the proportion of patients who remain transfusion-free and do not require a transfusion per protocol specified guidelines through Day 183, and haemolysis as measured by LDH normalisation (≤1× ULN, [246U/L]) from Days 29 through 183. Key secondary endpoints included: % change from baseline to Day 183 in LDH and quality of life (assessed via FACIT–F); proportion of patients with breakthrough haemolysis defined as ≥1 new or worsening sign or symptom of IVH (fatigue, haemoglobinuria, abdominal pain, dyspnoea, anaemia [Hb <10g/dL]), MAVEs [including thrombosis], dysphagia, or erectile dysfunction) in the presence of LDH ≥2× ULN after prior reduction of LDH to <1.5× ULN on treatment and proportion of patients with stabilised Hb (defined as avoidance of a ≥2g/dL decrease in Hb from baseline in the absence of transfusion).¹

†ULTOMIRIS^® dosing in the clinical trials was consistent with the recommendations in the ULTOMIRIS^® SmPC.⁴

‡Study 302 was a Phase 3 multicentre, randomised, active-controlled, open-label, non-inferiority study to evaluate the efficacy and safety of ULTOMIRIS^® vs SOLIRIS^® in SOLIRIS^®-experienced adult patients with a documented diagnosis of PNH. Patients were treated with ULTOMIRIS^® or SOLIRIS^® over a 26-week initial evaluation period. Key inclusion criteria: age ≥18 years, diagnosis of PNH, granulocyte or monocyte clone size ≥5%, clinically stable on SOLIRIS^® for at least 6 months. Key exclusion criteria: LDH levels >2× ULN in the 6 months before Day 1, MAVE within 6 months before Day 1, body weight <40 kg at screening. Primary endpoint was haemolysis as measured by percentage change in LDH levels from baseline to Day 183. Key secondary endpoints included: proportion of patients with breakthrough haemolysis, defined as ≥1 new or worsening symptom or sign of IVH (fatigue, haemoglobinuria, abdominal pain, shortness of breath [dyspnoea], anaemia [Hb <10 g/dL], MAVE [including thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥2× ULN after prior reduction of LDH to <1.5× ULN on treatment; change from baseline in quality of life (assessed via FACIT–F); transfusion avoidance, defined as the proportion of patients who remained transfusion free and did not require a transfusion per protocol-specified guidelines; and proportion of patients with stabilized Hb, defined as avoidance of a ≥2-g/dL decrease in Hb level from baseline in the absence of transfusion.²

^*Mean FACIT-Fatigue score for the general population was determined through assessment of 2,426 adults (n=1,074 males; n=1,352 females; mean age [SD]: 49.8 [17.4] years) in Germany between March 2015 and May 2015.¹⁴

^†Improvements in QoL were evident across the broad PNH patient population studied, including those receiving transfusions and/or non-stabilised Hb.³

CI, confidence interval; FACIT–F, Functional Assessment of Chronic Illness Therapy – Fatigue; Hb, haemaglobin; IVH, intravascular haemolysis; LDH, lactose dehydrogenase; LS, least squares; MAVE, major adverse vascular event; C5, complement component 5; OLE, open-label extension; PNH, paroxysmal nocturnal haemoglobinuria; QoL, quality of life; SmPC, Summary of Product Characteristics; ULN, upper limit of normal.

^*Data collected from Phase 3, open-label, single-arm, multicenter study in 13 paediatric patients with PNH (NCT03406507). The study assessed the long-term PKs & PDs (primary endpoints), efficacy, and safety of ravulizumab treatment in eculizumab-naïve (n=5) or eculizumab-experienced (n=8) paediatric patients (aged <18 years) with PNH during 26-week primary evaluation period and 4-year extension period. Of 13 enrolled patients, 12 patients completed the extension period, and 1 eculizumab-experienced patient stopped the treatment because of their choice to undergo bone marrow transplantation on day 341 of extension period.

^†The maintenance dosing schedule for ULTOMIRIS^® in adults and paediatric patients who weigh ≥20 kg is once every 8 weeks. For paediatric patients who weigh ≥10 kg and <20 kg, the maintenance dosing schedule is once every 4 weeks.