ONE-YEAR EFFICACY OF RAVULIZUMAB (ALXN1210) IN ADULT PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA NAIVE TO COMPLEMENT INHIBITORS
Author(s): ,
Hubert Schrezenmeier
Affiliations:
Institute of Transfusion Medicine, University of Ulm and Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service and University Hospital Ulm,Ulm,Germany
,
Austin Kulasekararaj
Affiliations:
Department of Haematological Medicine,King’s College Hospital, NIHR/Wellcome King’s Clinical Research Facility,London,United Kingdom
,
Lindsay Mitchell
Affiliations:
University Hospital Monklands,North Lanarkshire,United Kingdom
,
Flore Sicre de Fontbrune
Affiliations:
Centre de Référence Aplasie Médullaire, Service d'Hématologie Greffe,Assistance Publique des Hôpitaux de Paris, Hôpital Saint-Louis,Paris,France
,
Timothy Devos
Affiliations:
Department of Hematology,University Hospitals Leuven,Leuven,Belgium;Laboratory of Experimental Transplantation, Department of Microbiology and Immunology,KU Leuven,Leuven,Belgium
,
Shinichiro Okamoto
Affiliations:
Keio University School of Medicine,Tokyo,Japan
,
Richard Wells
Affiliations:
Sunnybrook Health Sciences Centre,Toronto,Canada
,
Scott Rottinghaus
Affiliations:
Alexion Pharmaceuticals, Inc.,New Haven,United States
,
Peng Liu
Affiliations:
Alexion Pharmaceuticals, Inc.,New Haven,United States
,
Stephan Ortiz
Affiliations:
Alexion Pharmaceuticals, Inc.,New Haven,United States
,
Lori Shafner
Affiliations:
Alexion Pharmaceuticals, Inc.,New Haven,United States
,
Jong Wook Lee
Affiliations:
Seoul St. Mary’s Hospital, The Catholic University of Korea,Seoul,Korea, Republic Of
Gerard Socie
Affiliations:
Hôpital Saint-Louis,Paris,France
EHA Library. Schrezenmeier H. Jun 15, 2019; 267446; S863
Hubert Schrezenmeier
Hubert Schrezenmeier
Contributions
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Abstract

Abstract: S863

Type: Oral Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 12:00 - 12:15

Location: Hall E106

Background
Ravulizumab, a novel C5 complement inhibitor, was approved by FDA for treating paroxysmal nocturnal hemoglobinuria (PNH) and is under review in EMEA and Japan. In the largest phase 3 study in complement inhibitor-naive PNH patients (pts) conducted to date, qw8 ravulizumab was noninferior to qw2 eculizumab for all primary and secondary endpoints after 26 wks. To evaluate long-term efficacy and safety, all pts had the option of continuing to receive ravulizumab in an extension study.

Aims
To characterize the durability of efficacy responses to ravulizumab through 52 wks and to evaluate the efficacy profile of ravulizumab after switching from eculizumab in adult PNH pts naive to eculizumab therapy (NCT02946463).

Methods
This phase 3, randomized, active-controlled, open-label study was conducted in 123 centers in 25 countries. Pts were randomly assigned to receive eculizumab (n=121) or ravulizumab (n=125) for 26 wks, after which pts in the ravulizumab arm continued ravulizumab maintenance therapy (R-R arm), while pts in the eculizumab arm were then switched to ravulizumab (E-R arm). Results of the co-primary [lactate dehydrogenase normalization (LDH-N), transfusion avoidance] and key secondary endpoints [breakthrough hemolysis (BTH) and LDH levels] are provided descriptively. Plasma free C5 levels were obtained through 52 wks.

Results
During the first 26 wks, 74% of pts in the R-R arm avoided transfusion, compared to 77% avoiding transfusion in wks 27-52. More than 90% (n=83) of pts who avoided transfusion during the initial 26 wk period maintained this response through 52 wks, and 38% (n=12) who required transfusion in the 0-26 wk period avoided it in wks 27-52. In the E-R arm, 66% (26 wks) vs 67% (52 wks) avoided transfusion; 87% (n=69) who avoided transfusion for 26 wks maintained this response through 52 wks. Additionally, 28% (n=11) who required transfusion during the 26 wks while on eculizumab avoided it through 52 wks once switched to ravulizumab. In the R-R arm, LDH-N occurred in 48% of pts (n=60) at 26 wks and in 44% of pts (n=54) at 52 wks. Similarly, in the E-R arm, at 26 wks, LDH-N was 42%, and was 40% at 52 wks. At the end of 26 wks, pts on ravulizumab had a 77% (SEM = 1.4) mean reduction in LDH from baseline and this was maintained through 52 wks (77%, SEM=1.2). All pts (n=119) in the ravulizumab treatment group continued to maintain free C5 <0.5 µg/mL at all time points through 52 wks (Figure). In pts initially randomized to eculizumab, the switch to ravulizumab showed improved free C5 control, and no patients had free C5 >0.5 µg/ml after the switch. Of the 125 pts initially on ravulizumab, 5 pts (4%) had BTH in the first 26 wks vs 4 pts (3%) during wks 27-52. In the E-R arm, 13 pts (11%) experienced BTH during the first 26 wks vs 2 pts (2%) in wks 27-52 after the switch to ravulizumab. During wks 27-52, none of the BTH events in both arms were associated with free C5 >0.5 µg/ml, the threshold associated with complete inhibition of hemolysis. These results demonstrate maintenance of complete free C5 control in pts receiving ravulizumab. Ravulizumab was well tolerated and the most common treatment-related adverse events decreased in frequency with increased treatment duration.

Conclusion
Ravulizumab demonstrated consistent and durable efficacy over 52 wks of treatment. Importantly, all pts who had suboptimal free C5 control receiving eculizumab achieved complete free C5 inhibition after the switch to ravulizumab. Complete suppression of free C5 level was associated with a decreased incidence of BTH.

Session topic: 12. Bone marrow failure syndromes incl. PNH - Clinical

Keyword(s): Clinical trial, Long-term follow-up, PNH, Treatment

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