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OVERVIEW

ADZYNMA is an enzyme replacement therapy (ERT) indicated for the treatment of ADAMTS13 deficiency in children and adult patients with congenital thrombotic thrombocytopenic purpura (cTTP). ADZYNMA can be used for all age groups.*,1 

ADZYNMA is a purified bivariant human recombinant “A disintegrin and metalloproteinase with thrombospondin motifs 13” (rADAMTS13) expressed in Chinese Hamster Ovary (CHO) cells using recombinant DNA technology (a mixture of native rADAMTS13 Q23 and variant rADAMTS13 R23 with a controlled range of the two variants ratio), referred to as rADAMTS13.1

A Phase 1, first-in-human, dose escalation, safety, and pharmacokinetics study in cTTP patients (NCT02216084)3,4

A pivotal, randomised, controlled Phase 3 study in cTTP patients 
(NCT03393975)5

A Phase 3b continuation study in cTTP patients (NCT04683003)6


The ADZYNMA clinical development programme included a pivotal, randomised, controlled Phase 3 study, the first of its kind in cTTP patients2,3


ADZYNMA Phase 3 study design1,2

A Phase 3, multinational, prospective, open label, randomised, controlled, two period crossover trial to evaluate the efficacy and safety of ADZYNMA and standard therapy administered as routine prophylaxis or on demand treatment in patients with congenital TTP.2

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All patients rolled over to a 6 month ADZYNMA extension.
 

The Phase 3 study had a cohort of acute cTTP patients who received ADZYNMA on demand. Patients were eligible to enter the prophylaxis study upon completion of acute treatment.

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Adapted from Scully M, et al. N Engl J Med. 2024;390(17):1584-1596.

A Phase 3 study aimed to assess the safety and efficacy of ADZYNMA in the prevention and treatment of acute episodes of thrombotic thrombocytopenic purpura (TTP) in patients with congenital TTP.2
The study evaluated the clinical benefit of ADZYNMA across efficacy, pharmacokinetic, safety, and immunogenicity endpoints in patients with severe cTTP.5

Patients could be enrolled to prophylaxis treatment and were randomised one-to-one in a Phase 3, open-label, crossover trial 
(NCT03393975) to receive either ADZYNMA followed by plasma-based therapies or plasmabased therapies followed by ADZYNMA.2

In addition to the cohort receiving prophylactic treatment in the Phase 3 study, a cohort included patients entering the trial to control an acute event with on-demand treatment. When patients experienced an event, they were randomised one-to-one to receive either ADZYNMA or plasma-based therapies until the acute TTP event was resolved. After resolution, patients could opt to join the prophylactic cohort.2

STUDY PATIENT POPULATION1,2

Patients with severe congenital deficiency of ADAMTS13 (cTTP; defined as plasma ADAMTS13 activity <10%) aged 0–70 years.

INTERVENTION1,2

ADZYNMA

Prophylaxis dose regimen:

  • 40 IU/kg body weight of ADZYNMA once every other week.


On-demand dose regimen:

  • Day 1: Administer 40 IU/kg body weight of ADZYNMA.
  • Day 2: Administer 20 IU/kg body weight of ADZYNMA.
  • Day 3 and thereafter: 15 IU/kg of body weight once daily until two days after the acute event was resolved.

COMPARATOR1,2

Investigator-recommended plasma-based therapies.

OUTCOMES1,2
  • The primary outcome measure was the incidence of acute TTP events.*
  • Secondary endpoints included the number and incidence of acute cTTP episodes responding to ADZYNMA; time to resolution of clinical symptoms and laboratory parameters; incidence of isolated clinical symptoms (including thrombocytopenia, microangiopathic haemolytic anaemia (MAHA), renal dysfunction, neurological symptoms, and abdominal pain); incidence of adverse events; incidence of antibodies to ADAMTS13; PK properties; health-related quality of life; and resource utilization.
  • Exploratory outcome measures included the incidence of subacute (or non-acute) manifestations in patients receiving prophylactic treatment, measured as incidence of composite TTP manifestations (defined as the occurrence of two or more of the following: thrombocytopenia, microangiopathic haemolytic anaemia, renal dysfunction, neurological symptoms or abdominal pain).

*An acute TTP event was defined as a decrease in the platelet count by at least 50% from baseline or to less than 100,000 per microlitre and an elevation of the lactate dehydrogenase (LDH) level to more than 2 times the baseline value or more than 2 times the upper limit of the normal range (ULN).2

 

Explore the prophylactic, on-demand and quality of life (QoL) benefits with ADZYNMA compared with plasma-based therapies

Efficacy

Discover the safety, tolerability and immunogenicity profile associated with ADZYNMA
 

Safety


ADZYNMA is now an option for cTTP prophylaxis and treatment*,9

Takeda is committed to advancing treatment options in rare genetics and haematology

This is a step forward in the management of cTTP and brings new possibilities to patients

Takeda is committed to advancing disease management, including treatment options and improving quality of life for those living with cTTP

*Physicians must educate patients and parents on the benefits of prophylaxis to ensure adherence for adequate protection against cTTP relapses.


 

  1. ADZYNMA (rADAMTS13) EU Summary of Product Characteristics. August 2024.
  2. Scully M, et al. N Engl J Med. 2024; 390(17):1584-1596.
  3. Scully, M, et al. Blood. 2017; 130(19):2055-2063.
  4. Phase 1 Dose Escalation, Single Dose Study to Assess Safety and Pharmacokinetics of BAX930 in Hereditary Thrombotic Thrombocytopenic Purpura (TTP). Available at: https://www.clinicaltrials.gov/study/NCT02216084. Accessed July 2024.
  5. A Study of BAX 930 in Children, Teenagers, and Adults Born With Thrombotic Thrombocytopenic Purpura (TTP). Available at: https://clinicaltrials.gov/study/NCT03393975. Accessed July 2024.
  6. A Study of TAK-755 in Participants With Congenital Thrombotic Thrombocytopenic Purpura. Available at: https://clinicaltrials.gov/study/NCT04683003. Accessed July 2024.
  7. Takeda Press Release. 5th January 2023. Available at: https://www.takeda.com/newsroom/newsreleases/2022/takeda-announces-favorablephase-3-safety-and-efficacy-results-of-tak-755-as-compared-to-standard-of-care-in-congenital-thrombotic-thrombocytopenic-purpura-cttp/. Accessed July 2024.
  8. Takeda Press Release. 26th March 2024. Available at: https://www.takeda.com/newsroom/newsreleases/2024/adzynma-japan-regulatory-approval/. Accessed July 2024.
  9. Mazepa, M. Blood. 2022; 140(7):671 672.

 

ADAMTS13, A disintegrin and metalloproteinase with a thrombospondin motifs 13
CHO, Chinese hamster ovary
cTTP, Congenital TTP
DNA, Deoxyribonucleic acid
ERT, Enzyme replacement therapy
IU, International unit
LDH, Lactate dehydrogenase
MAHA, Microangiopathic haemolytic anaemia
PK, Pharmacokinetic
QoL, Quality of life
rADAMTS13, Recombinant ADAMTS13
SmPC, Summary of product characteristics
SoC, Standard of care
TTP, Thrombotic thrombocytopenic purpura
Tx, Treatment
ULN, Upper limit of normal

 

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