One-year efficacy and safety of ravulizumab in adults with paroxysmal nocturnal hemoglobinuria naïve to complement inhibitor therapy: open-label extension of a randomized study
Creators: name: Schrezenmeier, Hubert
name: Kulasekararaj, Austin
name: Mitchell, Lindsay
name: Sicre De Fontbrune, Flore
name: Devos, Timothy
name: Okamoto, Shinichiro
name: Wells, Richard
name: Rottinghaus, Scott T.
name: Liu, Peng
name: Ortiz, Stephan
name: Lee, Jong Wook
name: Socié, Gérard
Publisher: name: Universität Ulm
Year: 2020
Subjects: subject: breakthrough hemolysis
subject: complement inhibitor
subject: eculizumab
subject: high disease activity
subject: paroxysmal nocturnal hemoglobinuria
subject: ravulizumab
subject: transfusion
subject: DDC 610 / Medicine &amp; health
subject: Hemoglobinuria, Paroxysmal; Drug therapy
subject: Lactate dehydrogenases
subject: Antibodies, Monoclonal, Humanized; Therapeutic use
subject: Complement inactivating agents
subject: Paroxysmale nächtliche Hämoglobinurie
subject: Pharmakotherapie
subject: Hämolyse

description: Background: Ravulizumab, the only long-acting complement C5 inhibitor for adults with paroxysmal nocturnal hemoglobinuria (PNH), demonstrated non-inferiority to eculizumab after 26 weeks of treatment in complement inhibitor-naïve patients during a phase III randomized controlled trial. We present open-label extension results with up to 52 weeks of treatment. Methods: Patients assigned to ravulizumab every 8 weeks (q8w) or eculizumab every 2 weeks during the randomized primary evaluation period received ravulizumab q8w during the 26-week extension. Efficacy endpoints were lactate dehydrogenase (LDH) normalization, transfusion avoidance, breakthrough hemolysis (BTH), LDH levels, Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale, and stabilized hemoglobin. Serum free C5 levels and safety were assessed. Outcomes as of the data cut-off (4 September 2018) were summarized using descriptive statistics. Results: Overall, 124 patients continued ravulizumab, and 119 switched from eculizumab to ravulizumab. During the extension, 43.5% and 40.3% of patients in the ravulizumab–ravulizumab and eculizumab–ravulizumab arms, respectively, achieved LDH normalization; 76.6% and 67.2% avoided transfusion. BTH decreased in the eculizumab–ravulizumab arm; no events were associated with free C5 ⩾0.5 μg/mL while receiving ravulizumab. Overall, 73.4% and 65.5% of patients in the ravulizumab–ravulizumab and eculizumab–ravulizumab arms, respectively, achieved stabilized hemoglobin. Similar proportions of patients achieved ⩾3-point improvement in FACIT-Fatigue at week 52 (ravulizumab–ravulizumab, 64.5%; eculizumab–ravulizumab, 57.1%). All patients maintained free C5 &lt;0.5 μg/mL during the ravulizumab extension, including those who experienced C5 excursions ⩾0.5 μg/mL while receiving eculizumab during the primary evaluation period. Adverse events were comparable between groups and decreased over time. Conclusion: In adult, complement inhibitor–naïve patients with PNH, ravulizumab q8w for up to 52 weeks demonstrated durable efficacy and was well tolerated, with complete and sustained free C5 inhibition and a decreased incidence of BTH with no events associated with loss of free C5 control. Trial registration: ClinicalTrials.gov identifier, NCT02946463