Phase IIIb/IV PROPEL trial of Adynovate presents new data in haemophilia A.- Takeda

Takeda announced results from its phase IIIb/IV PROPEL trial for Adynovate (recombinant factor VIII), a PROspective, randomized, multi-center study comparing the safety and efficacy of Adynovate following PK-guided prophylaxis targeting two different Factor Eight (FVIII) trough Levels in subjects with severe hemophilia A. The study showed that Adynovate prophylaxis targeting 8�12% (HIGH) vs 1�3 % (LOW) trough levels was associated with a trend toward a higher proportion of patients with a total annualized all bleed rate (ABR)=0 (66% HIGH vs 39% LOW; p=0.075).

The HIGH group was also associated with a trend toward a lower total ABR, as well as a higher proportion of patients with all annualized joint bleed rate (AJBR)=0 (90% HIGH vs 68% LOW) and all spontaneous ABR=0 (84% HIGH vs 61% LOW). The data suggests that optimizing FVIII profiles through PK-driven dosing that targets trough levels 8-12% was consistently achievable and further treatment personalization for patients with hemophilia A should be considered. Safety profiles were comparable and consistent with previous Adynovate trials. Overall AEs and SAEs occurred in 63% and 9% of subjects, with 1 HIGH subject (0.9%) SAE considered related to SHP660: a transient 0.6 BU inhibitor without evidence of anti-FVIII binding, which resolved by study end. AE profiles were comparable and consistent with previous SHP660 trials.

Ongoing analyses will characterize the relationship between PK-tailored dosing of Adynovate FVIII levels and bleeding events. Data were presented at the 12th Annual Congress of the European Association of Haemophilia and Allied Disorders.