OC 14.1 - Phase 3 prospective, randomized, controlled, open-label, multicenter, crossover study of recombinant ADAMTS13 in patients with congenital thrombotic thrombocytopenic purpura

Sunday, June 25, 2023

10:45 – 11:00 ET

Room: 520

Session Available As: On-Demand

Presenting Author(s)

Marie Scully, MD

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

Co-Author(s)

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
BM

Björn Mellgård

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

Thomas L Ortel

Professor of Medicine & Pathology
Duke University, Durham, NC, USA
Durham, North Carolina, United States
HL

Hong Li

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

Mila Ayash-Rashkovsky

Director Clinical Programs
Takeda Development Center Americas, Inc., Cambridge, MA, USA
Cambridge, Massachusetts, United States
Spero Cataland, MD (he/him/his)

Professor
Department of Internal Medicine, Ohio State University, Columbus, OH, USA
Westerville, Ohio, United States
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 an ultra-rare, potentially life-threatening thrombotic microangiopathy caused by an ADAMTS13 deficiency. An ongoing pivotal study is investigating recombinant ADAMTS13 (rADAMTS13; TAK-755; Takeda Development Center Americas, Inc., Lexington, MA, USA) prophylaxis as a therapeutic option in patients with cTTP.

Aims: To evaluate the efficacy/safety of rADAMTS13 prophylaxis.

Methods: This phase 3 prospective, randomized, controlled, open-label, multicenter, crossover study (NCT03393975) was open to enroll patients aged 0-70 years with confirmed cTTP. Data from a pre-planned interim analysis (data cutoff: August 12, 2022) are presented. Patients were randomized 1:1 to 40 IU/kg intravenous rADAMTS13 or standard of care (SoC; Table); both administered every other week or weekly, based on regimen at enrollment. Patients received rADAMTS13 or SoC for Months 1-6 (Period 1), crossing over to the alternate treatment for Months 7-12 (Period 2); patients received rADAMTS13 for Months 13-18 (Period 3). The primary outcome was incidence of acute TTP events in Periods 1-3. Secondary outcomes included non-acute TTP manifestation incidence, treatment-emergent adverse events (TEAEs), serious AEs (SAEs), and immunogenicity.

Results: Efficacy data from 38 adult/adolescent patients with cTTP were analyzed (modified full analysis set: age: 12-58 years; 61% female; mean rADAMTS13 exposure: 13.2 months). Zero acute TTP events occurred during rADAMTS13 prophylaxis; one event occurred during SoC. rADAMTS13 prophylaxis generally resulted in lower non-acute TTP manifestation rates versus SoC (Table). TEAEs assessed as treatment related were reported in 10.3% (n=39) of patients receiving rADAMTS13 and 50.0% (n=40) receiving SoC (safety analysis set, 12-68 years). No rADAMTS13-related SAEs were reported. No patients with cTTP developed ADAMTS13 neutralizing antibodies.

Conclusion(s): No acute TTP events occurred during 13.2 months (mean exposure) with rADAMTS13 prophylaxis. Incidence of non-acute TTP manifestations was generally lower with rADAMTS13 versus SoC. No rADAMTS13-related SAEs or immunogenicity were identified. rADAMTS13 is a promising, potential therapeutic approach for patients with cTTP.

Learning Objectives:

Gain an understanding of results from the first randomized, controlled trial comparing the efficacy and safety of rADAMTS13 prophylaxis with SoC in patients with cTTP
Recognize unmet needs in patients with cTTP receiving Standard of care
Gain an understanding of the safety profile of rADAMTS13, including the absence of allergic reactions to rADAMTS13.