In patients with congenital thrombotic thrombocytopenic purpura (TTP), there were no acute TTP events in a preplanned interim analysis of a phase 3 study evaluating the use of recombinant ADAMTS13 (rADAMTS13) prophylaxis. Study findings were presented at the International Society on Thrombosis and Haemostasis (ISTH) 2023 Congress by Marie Scully, MD, of the University College London Hospitals in London, UK, and colleagues.

This open-label, multicenter, crossover phase 3 study ( Identifier: NCT03393975) enrolled patients aged 0 to 70 years with severe congenital TTP. In the prophylaxis cohort of this study, patients were randomly assigned 1:1 to either rADAMTS13 treatment (40 IU/kg) or standard of care for 6 months (period 1), before crossing over to the other treatment (rADAMTS13 or standard of care) for 6 months in period 2.

In period 3, all patients received rADAMTS13 for 6 months. With this interim analysis, the estimated non-model-based annualized acute TTP event rate was reported, and patients had a median exposure to rADAMTS13 prophylaxis of 13.2 months.

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There were 48 patients overall in this study, and they had a median age of 32.5 years (range, 3-68). In 44 evaluable patients, the median ADAMTS13 activity prior to receiving any congenital TTP treatment was 5.0% (range, 0%-10.0%).

There were 8 patients (16.7%) with a history of acute TTP events during the prior 12 months. The modified full analysis population included 46 patients, 21 of whom received rADAMTS13 prior to standard of care therapy, and 25 of whom received standard of care therapy prior to rADAMTS13.

In a subset of patients who were aged 12 years and older, with rADAMTS13 in periods 1 and 2, the mean annualized acute TTP event rate was 0, compared with 0.05 (SD, 0.28) with standard of care. The mean annualized subacute TTP event rates across these periods were 0 and 0.25 (SD, 0.78), respectively. In period 3, with rADAMTS13, the mean annualized acute TTP event rate was 0, while the mean annualized subacute TTP event rate was 0.07 (SD, 0.29).

In safety analysis including 48 patients, treatment-emergent adverse events (TEAEs) that were considered related to treatment were reported in 8.9% of patients with rADAMTS13 and in 47.7% with standard of care during periods 1 and 2, and in 2.8% of patients with rADAMTS13 during period 3.

Treatment-related serious TEAEs were reported to occur in 2.3% of patients receiving standard of care in periods 1 and 2, but none were reported in patients receiving rADAMTS13 in periods 1 through 3. Overall, there were reportedly no TEAEs leading to death, and no neutralizing antibodies appeared to develop while patients were on rADAMTS13 prophylaxis.

In her presentation, Dr Scully emphasized the lack of acute TTP events, in addition to safety and tolerability findings with rADAMTS13 prophylaxis shown in this analysis. In her presentation, she stated, “this is an extremely promising therapeutic approach for all patients with congenital TTP.”

Disclosures: This research was supported by Takeda Development Center Americas, Inc., and Baxalta Innovations GmbH, a Takeda company. Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.


Scully M, Windyga J, Mellgàrd B, et al. Phase 3 prospective, randomized, controlled, open-label, multicenter, crossover study of recombinant ADAMTS13 in patients with congenital thrombotic thrombocytopenic purpura. ISTH 2023 Congress; June 24-28, 2023. Abstract OC 14.1.