Michael Denne, PharmD, Vice President of US Medical Affairs at Takeda, discusses results from clinical trials evaluating rADAMTS13 in patients with congenital thrombotic thrombocytopenic purpura (cTTP).
cTTP is characterized by profound peripheral thrombocytopenia, microangiopathic hemolytic anemia (MAHA) and single or multiple organ failure of variable severity. It is caused by deficiency of the ADAMTS13 enzyme.
Patients completing the Phase 3 study could enroll into the Phase 3b open-label continuation study. The phase 3 clinical trial was a prospective, randomized, controlled, open-label, multicenter, two period crossover study involving eight pediatric patients. The phase 3b clinical trial was a prospective, open-label, multicenter, single treatment arm, continuation study involving six pediatric patients. Both studies evaluated the efficacy and safety of rADAMTS13 prophylaxis in patients with cTTP.
rADAMTS13 is the first recombinant form of human ADAMTS13 approved by the U.S. Food and Drug Administration (FDA). Patients were randomized to receive 40 IU/kg rADAMTS13 or standard of care prophylaxis. Treatment lasted for six months and patients were then crossed over to the alternate treatment for another six months. The primary outcome was incidence of acute TTP events. Secondary outcomes included incidence of non-acute TTP events, safety, and immunogenicity.
Results
In the phase 3 study, no acute TTP events were observed. The mean annualized event rare for subacute events in periods 1 and 2 were 0.23 ± 0.65 for rADAMTS13 and 0.51 ± 0.95 for standard of care. No subacute events were observed in period 3.
Thrombocytopenia mean annualized event rate was 2.98 ± 6.32 for rADAMTS13 prophylaxis vs 4.05 ± 7.62 for standard of care (periods 1 and 2), and 0.69 ± 1.96 (period 3). Mean annualized event rate for elevated lactate dehydrogenase (LDH) was 3.21 ± 8.37 for rADAMTS13 prophylaxis vs 3.00 ± 8.49 for standard of care (periods 1 and 2), and 2.90 ± 8.19 (period 3).
In the phase 3b study, the mean annualized event rate was 0.21 ± 0.51 for acute events and 0.41 ± 0.64 for subacute events. The mean annualized rate was 1.86 ± 2.04 for thrombocytopenia and 0.63 ± 1.05 for elevated LDH.
Additionally, in the phase 3 trial, 39 adverse events were reported in 8 patients during rADAMTS13 prophylaxis, and 21 adverse events in 7 patients during standard of care (periods 1 and 2). During period 3, 17 adverse events were reported in 4 patients. In the Phase 3b study, 26 AEs were reported in 5 patients. However, no adverse events were considered to be related to rADAMTS13.
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To learn more about cTTP and other rare hematologic conditions, visit https://checkrare.com/diseases/hematologic-disorders/
