OC 14.4 - Recombinant ADAMTS13 prophylaxis in patients with congenital thrombotic thrombocytopenic purpura: interim analysis from phase 3b continuation study

Sunday, June 25, 2023

11:30 – 11:45 ET

Room: 520

Session Available As: On-Demand

Presenting Author(s)

Paul Coppo, MD, PhD (he/him/his)

Professor
National Reference Center for Thrombotic Microangiopathy, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris and Sorbonne – Université (AP-HP.6), Paris, France
Paris, Ile-de-France, France

Co-Author(s)

PP

Parth Patwari

Medical Director, Clinical Sciences, Rare Diseases and Hematology
Takeda Development Center Americas, Inc., Cambridge, MA, USA
Cambridge, Massachusetts, United States
BM

Björn Mellgård

Vice President, Global Program Lead, Rare Genetics and Hematology
Takeda Development Center Americas, Inc., Cambridge, MA, USA
Cambridge, Massachusetts, United States
HL

Hong Li

Director Statistics
Takeda Development Center Americas, Inc., Cambridge, MA, USA
Cambridge, Massachusetts, United States
Marie Scully, MD

Professor of Haemostasis and Thrombosis
Department of Haematology, University College London Hospitals, London, UK
London, England, United Kingdom
MM

Masanori Matsumoto

Professor
Department of Blood Transfusion Medicine, Nara Medical University, Kashihara, Nara, Japan
Kashihara, Nara, Japan
Jerzy Windyga, Prof. dr med. (he/him/his)

Head Department of Hemostasis Disorders and Internal Medicine
Institute of Hematology and Transfusion Medicine
Warsaw, Mazowieckie, Poland
TO

Thomas L Ortel

Professor of Medicine & Pathology
Duke University, Durham, NC, USA
Durham, North Carolina, United States
Spero Cataland, MD (he/him/his)

Professor
Department of Internal Medicine, Ohio State University, Columbus, OH, USA
Westerville, Ohio, United States
Paul Knoebl, MD

Professor
Department of Medicine 1, Division of Hematology and Hemostasis, Medical University of Vienna, Vienna, Austria
Vienna, Wien, Austria
ZY

Ziqiang Yu

Professor
National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
Suzhou, Jiangsu, China (People's Republic)
LW

Linda T Wang

Executive Medical Director, Clinical Sciences, Rare Diseases and Hematology
Takeda Development Center Americas, Inc., Cambridge, MA, USA
Cambridge, Massachusetts, United States

Background: Congenital thrombotic thrombocytopenic purpura (cTTP) is a rare, potentially life-threatening disease resulting from severe ADAMTS13 deficiency. Chronic organ injury requires prophylaxis with plasma infusions, which is burdensome. Long-term prophylaxis with recombinant ADAMTS13 (rADAMTS13; TAK-755; Takeda Development Center Americas, Inc., Lexington, MA, USA) is being investigated in a phase 3b continuation study.

Aims: To evaluate the safety/efficacy of rADAMTS13 long-term prophylaxis in patients with cTTP.

Methods: This phase 3b, prospective, open-label, multicenter, continuation study (NCT04683003) enrolled cTTP patients aged 0-70 years. Patients had previously received prophylaxis with rADAMTS13 (12 months) and standard of care (plasma infusion; 6 months) in a randomized, crossover, pivotal trial (NCT03393975) (rollover cohort), or had not participated in the pivotal study (non-rollover cohort). Rollover cohort data from a pre-planned interim analysis (data cutoff: August 12, 2022) are presented. Patients received intravenous rADAMTS13 40 IU/kg prophylaxis weekly or every other week. The primary outcome was long-term safety/tolerability, as assessed by incidence of adverse events (AEs) and serious AEs (SAEs) that were considered related to rADAMTS13. Secondary outcomes included incidences of acute and subacute TTP events and non-acute TTP manifestations.

Results: Data from 29 patients were analyzed (mean±SD age: 40.4±12.1 years; 62% female). The median (range) duration of rADAMTS13 treatment was 0.7 (0-1.4) years. No treatment-related AEs were observed and no AEs led to rADAMTS13 discontinuation (Table 1). No patients developed ADAMTS13 neutralizing antibodies. Zero acute TTP events occurred during rADAMTS13 prophylaxis, and the incidence rates of subacute TTP events and TTP manifestations were comparable to those with rADAMTS13 prophylaxis in the pivotal study, and mostly lower versus previous SOC (Table 2).

Conclusion(s): In the rollover cohort of this continuation study, no adverse drug reactions were identified with rADAMTS13 prophylaxis, and no neutralizing antibodies developed. Treatment with rADAMTS13 continued for ≤1.4 years prevented acute TTP events, and reduced subacute events and TTP manifestations.

Learning Objectives:

Gain an understanding of results from a continuation trial assessing the long-term safety of rADAMTS13 prophylaxis in patients with cTTP.
Review the lack of immunogenicity with long-term rADAMTS13 prophylaxis in patients with cTTP.
Understand the impact of rADAMTS13 prophylaxis on TTP manifestations from the pivotal study to the continuation trial.