LB 01.1 - Safety, tolerability, and efficacy of mezagitamab (TAK-079) in chronic or persistent primary immune thrombocytopenia: Interim results from a phase 2, randomized, double-blind, placebo-controlled study

Sunday, June 23, 2024

09:30 – 09:45 ICT

Room: Plenary Hall

Presenting Author(s)

David J. Kuter, MD, DPhil

Chief of Hematology
Hematology Division, Massachusetts General Hospital, Harvard Medical School
Boston, Massachusetts, United States

Co-Author(s)

DP

Dražen Pulanić

Head of the Unit for Hemostasis
Thrombosis and Benign Hematology Disorders, Division of Hematology, Department of Internal Medicine, University Hospital Center Zagreb
Zagreb, Grad Zagreb, Croatia
AP

Andrea Patriarca

Director of Therapeutic Innovation in Hematology
AOU Maggiore della Carità and University of Eastern Piedmont
Novara, Piemonte, Italy
Renchi Yang, MD

Head of Thrombosis and Hemostasis Center
Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Tianjin, Hebei, China (People's Republic)
KS

Katya Sapunarova

Chief Assistant Professor
Department of Hematology, Medical University of Plodiv
Plodiv, Plovdiv, Bulgaria
KM

Katsuhiro Miura

Director
Department of Hematology and Oncology, Nihon University Itabashi Hospital
Tokyo, Tokyo, Japan
MF

MK Farmer

Senior Medical Director
Takeda Development Center Americas, Inc.
Cambridge, Massachusetts, United States
SW

Scarlett Wang

Associate Director, Statistics
Takeda Development Center Americas, Inc.
Cambridge, Massachusetts, United States
AS

Aimee Sundberg

Senior Director, Clinical Science
Takeda Development Center Americas, Inc.
Cambridge, Massachusetts, United States

Background: Immune thrombocytopenia (ITP) is a rare autoimmune bleeding disorder characterized by a reduction in platelet numbers and consequent hemorrhagic risk. Mezagitamab, a fully human anti-CD38 IgG1 monoclonal antibody, depletes CD38-expressing cells targeting cell- and antibody-mediated platelet destruction underlying ITP etiology.

Aims: Evaluate safety/tolerability and efficacy of mezagitamab in individuals with chronic/persistent ITP.

Methods: This Phase 2 study had two parts: 25 participants were randomized (1:1:1) to mezagitamab 100mg or 300mg, or placebo in Part A; 16 participants were randomized (2:1) to mezagitamab 600mg or placebo in Part B. Ethics committee approvals/informed consent were obtained. Participants received once weekly subcutaneous mezagitamab or placebo for 8 doses, followed by ≥8 weeks of safety follow-up. Stable background ITP treatment was continued during the study. Primary endpoint was percentage of participants with treatment-emergent adverse events (TEAEs). Secondary endpoints included platelet response (PR), complete platelet response (CPR), clinically meaningful platelet response (CMPR), and hemostatic platelet response (HPR).

Results: Participants (N=41) had a mean disease duration of 10.98 (range:0.3–35.2) years and received a mean of 3.9 (range:1–13) prior ITP treatments. In the prespecified interim analysis, TEAE incidence was similar between mezagitamab-treated and placebo-treated participants. In mezagitamab-treated versus placebo groups, 14.3% versus 0%, 17.9% versus 23.1%, and 14.3% versus 7.7% of participants had TEAEs leading to discontinuation, Grade ≥3 TEAEs, and serious adverse events, respectively. All three mezagitamab groups showed rapid/sustained improvement in platelet counts that persisted after the last dose through Week 16 (Figure 1). By Week 16, PR, CPR, CMPR, and HPR were higher in all mezagitamab dose groups versus placebo; highest responses were observed with mezagitamab 600mg (Figure 2). There were fewer participants with ≥1 ITP-associated bleeding AEs in mezagitamab-treated (17.9%) versus placebo (46.2%) groups.

Conclusion(s): Mezagitamab had a favorable safety/tolerability profile and demonstrated improvement in platelet response by Week 16 versus placebo in participants with chronic/persistent ITP.

Funding: Takeda