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ADZYNMA prophylaxis Primary endpoint: ADZYNMA prophylaxis for a median of ~ 13.3 months was associated with zero acute TTP events & fewer sub-acute TTP events compared to treatment with plasma-based therapies.^{*,†, 2 2. Scully M, et al. N Engl J Med. 2024;390(17):1584-1596.}

*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 2. Scully M, et al. N Engl J Med. 2024;390(17):1584-1596.
†} Subacute events were two or more of the following (including ≥1 laboratory measurement): a decrease in the platelet count by at least 25% from baseline or to less than 150,000 per microlitre, an increase in the LDH level to more than 1.5 times the baseline value or more than 1.5 times the ULN, or organ-specific signs or symptoms of TTP. ^{2 2. Scully M, et al. N Engl J Med. 2024;390(17):1584-1596.}

ADZYNMA prophylaxis resulted in higher mean platelet counts over time vs plasma-based therapies ^{1 1. ADZYNMA (rADAMTS13) EU Summary of Product Characteristics. August 2024. 2 2. Scully M, et al. N Engl J Med. 2024;390(17):1584-1596.}

Higher protection against thrombocytopenia achieved with ADZYNMA vs plasma-based therapies ^{1 1. ADZYNMA (rADAMTS13) EU Summary of Product Characteristics. August 2024. 3 3. Patel M, et al. Blood. 2023;142(Suppl 1):1260}

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The mean maximum ADAMTS13 activity after recombinant ADAMTS13 treatment was 101%, as compared with 19% after standard therapy. ^{2 2. Scully M, et al. N Engl J Med. 2024;390(17):1584-1596.}

Prophylactic treatment with ADZYNMA in the Phase 3, open-label, crossover trial (NCT03393975) resulted in a lower annualised incidence rate of composite TTP manifestations (at least one of the following: thrombocytopenia, elevated LDH level, increased creatinine level, neurological symptoms, or abdominal pain) vs plasma-based therapy. ^{1 1. ADZYNMA (rADAMTS13) EU Summary of Product Characteristics. August 2024. 2 2. Scully M, et al. N Engl J Med. 2024;390(17):1584-1596.}

Thrombocytopenia was the most frequently observed TTP manifestation ^{1 1. ADZYNMA (rADAMTS13) EU Summary of Product Characteristics. August 2024. 2 2. Scully M, et al. N Engl J Med. 2024;390(17):1584-1596.}

No acute TTP event occurred during prophylaxis with recombinant ADAMTS13, whereas 1 patient had an acute TTP event during prophylaxis with standard therapy (mean annualised event rate, 0.05) ^{1 1. ADZYNMA (rADAMTS13) EU Summary of Product Characteristics. August 2024. 2 2. Scully M, et al. N Engl J Med. 2024;390(17):1584-1596.}

ADZYNMA pharmacology

ADZYNMA IV administration at 40 IU/kg resulted in approximately greater than 5-fold higher ADAMTS13 activity exposures (Cmax, AUC, and duration above 10% ADAMTS13 activity) and lower variability when compared to plasma-based therapies.^{*, 1 1. ADZYNMA (rADAMTS13) EU Summary of Product Characteristics. August 2024.}

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✓  The mean maximum ADAMTS13 activity after recombinant ADAMTS13 treatment was 101%, as compared with 19% after standard therapy.  ^{2 2. Scully M, et al. N Engl J Med. 2024;390(17):1584-1596.}

✓  ADZYNMA IV administration at 40 IU/kg resulted in approximately greater than 5-fold higher ADAMTS13 activity exposures (Cmax, AUC, and duration above 10% ADAMTS13 activity) and lower variability when compared to plasma-based therapies.^{*, 1 1. ADZYNMA (rADAMTS13) EU Summary of Product Characteristics. August 2024.}

✓  In a Phase 3, open-label, crossover trial (NCT03393975), the mean time with ADAMTS13 activity of ≥10% was 5.2 days after ADZYNMA administration vs 1.7 days after standard therapy. ^{1 1. ADZYNMA (rADAMTS13) EU Summary of Product Characteristics. August 2024. 2 2. Scully M, et al. N Engl J Med. 2024;390(17):1584-1596.}

✓ The prophylactic dose of ADZYNMA is 40 IU/kg of body weight, administered once every other week. The prophylaxis dosing frequency may be adjusted to 40 IU/kg of body weight once weekly based on clinical response. ¹ 1. ADZYNMA (rADAMTS13) EU Summary of Product Characteristics. August 2024.

✓  Prophylactic treatment with ADZYNMA in the Phase 3, open-label, crossover trial (NCT03393975) resulted in a lower annualised incidence rate of composite cTTP manifestations (at least one of the following: thrombocytopenia, elevated LDH level, increased creatinine level, neurological symptoms, or abdominal pain) vs plasma-based therapy. ^{1 1. ADZYNMA (rADAMTS13) EU Summary of Product Characteristics. August 2024. 2 2. Scully M, et al. N Engl J Med. 2024;390(17):1584-1596.}

*The PK profile of ADZYNMA was determined based on clinical trial ADAMTS13 activity data analyses. Following single-dose intravenous administration of ADZYNMA at 5 IU/kg, 20 IU/kg, and 40 IU/kg to adults and adolescents, dose-related increases in individual ADAMTS13 activity were observed and reached a maximum at approximately 1 hour post-administration or earlier. ¹ 1. ADZYNMA (rADAMTS13) EU Summary of Product Characteristics. August 2024.

ADZYNMA indication

ADZYNMA can be used prophylactically, and on-demand, to treat congenital TTP in children and adults.^{*, 1 1. ADZYNMA (rADAMTS13) EU Summary of Product Characteristics. August 2024.}

ADZYNMA IV administration at 40 IU/kg resulted in approximately greater than 5-fold higher ADAMTS13 activity exposures (Cmax, AUC, and duration above 10% ADAMTS13 activity) and lower variability when compared to plasma-based therapies.^{*, 1 1. ADZYNMA (rADAMTS13) EU Summary of Product Characteristics. August 2024.}

* The PK profile of ADZYNMA was determined based on clinical trial ADAMTS13 activity data analyses. Following single-dose intravenous administration of ADZYNMA at 5 IU/kg, 20 IU/kg, and 40 IU/kg to adults and adolescents, dose-related increases in individual ADAMTS13 activity were observed and reached a maximum at approximately 1 hour post-administration or earlier. ¹ 1. ADZYNMA (rADAMTS13) EU Summary of Product Characteristics. August 2024.

Acronyms

ADAMTS13, A disintegrin and metalloproteinase with a thrombospondin motifs 13 AUC, Area under the plasma concentration-time curve
Cave,ss, Average plasma concentration at steady-state
CI, Confidence interval Cmax, Maximum plasma concentration
cTTP, Congenital TTP
CHO, Chinese hamster ovary
ERT, Enzyme replacement therapy
FFP, Fresh frozen plasma
FVIII, Factor VIII
IU, International unit
IV, Intravenous
LDH, Lactate dehydrogenase
LLOQ, Lower limit of quantification
PK, Pharmacokinetic
Q1W, Once weekly
Q2W, Once every two weeks
rADAMTS13, Recombinant ADAMTS13
S/D, Solvent detergent
SmPC, summary of product characteristics
SoC, Standard of care
TTP, Thrombotic thrombocytopenic purpura
ULN, Upper limit of normal