The novel design of the study was built upon preliminary data indicating that FVIII exposure associated with higher trough levels may be able to help enhance bleed protection and help more patients reach zero bleeds

Takeda Pharmaceutical Company Limited, the global biotechnology leader in rare diseases, has today announced results from its phase IIIb/IV clinical trial for ADYNOVATE at the 12th Annual Congress of the European Association of Haemophilia and Allied Disorders, EAHAD, taking place February 6-9, in Prague, Czech Republic. The PROPEL study is 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. Ongoing analyses will characterize the relationship between PK-tailored dosing of ADYNOVATE FVIII levels and bleeding events.

“The study reiterates the importance of personalised prophylaxis for those living with hemophilia,” Robert Klamroth, the head of the Department of Internal Medicine Angiology and Coagulation Disorders and director of the Comprehensive Care HaemophiliaTreatment Centre and the Haemostasis and Thrombosis Unit at the VivantesKlinikum in Berlin, Germany, said. “The findings suggest the need to measure actual FVIII levels and show a clear trend that if we’re able to keep FVIII levels in a higher range, there may be better patient outcomes, including enhanced bleed protection that could help more patients reach zero bleeds.”

“At Takeda, we are proud of the hematology heritage Shire and Baxalta built over 60 years and we plan on expanding on it through continued research and innovation, including continued focus on direct factor replacement,” WolfhardErdlenbruch, the vice-president, head of Global Medical Affairs Hematology, Takeda, said. “We are excited to be at EAHAD and share the results of PROPEL study. The zero all bleed rates and zero all spontaneous joint bleeds in this study have not been reported previously with people living with hemophilia A. This supports that factor levels matter and brings us a step closer to achieving our goal of optimized and personalized patient care, because every bleed matters.”

In addition to PROPEL, Takeda will present a dozen scientific data releases on the company’s recently acquired broad portfolio of treatments for bleeding disorders throughout EAHAD, including:

• AHEAD international and German studies: Effectiveness, safety, and quality of life outcomes in hemophilia A patients treated with antihemophilic factor (recombinant) in a real world setting over 5 years.
• Insights into the evolution of haemophiliacarthropathy: The Irish personalised approach to the treatment of haemophilia, iPATH, study.
• Physical activity and haemophilic joint arthropathy amongst adults with severe haemophilia in Ireland: The Irish personalised approach to the treatment of haemophilia, iPATH, study.
• Barriers to physical activity amongst adults with moderate and severe haemophilia in Ireland: The Irish personalised approach to the treatment of haemophilia, iPATH, study.
• Results from a phase 3B, open-label, multicenter, continuation study of rurioctocog alfa pegol for prophylaxis in previously treated patients with severe hemophilia A: Analysis by age group.
• Design of a phase 3, prospective, multicenter, open-label study of safety and hemostatic efficacy of rurioctocog alfa pegol in previously untreated patients <6 years of age with severe hemophilia A.
• Demographic and baseline data from patients with hemophilia and inhibitors enrolled in the FEIBA global outcomes, “FEIBA GO,” study.
• Analysis of joint bleeding events from a phase 3, multicenter, open-label study of on-demand recombinant von Willebrand factor, VWF, treatment in patients with severe von Willebrand disease, VWD.
• Evaluation of laboratory safety data from patients with severe von Willebrand disease, VWD, in association with infusion of recombinant von Willebrand factor, VWF, in a phase 3, multicenter, open-label study.
• Efficacy and safety of prophylaxis with recombinant von Willebrand factor, VWF, in severe von Willebrand disease, VWD: Design of a prospective, phase 3, open-label, international multicenter study.
• Nonclinical safety evaluation of a next generation factor IX, FIX, gene therapy construct (SHP648) in mice.

Feb. 8, 2019 @ 04:30 GMT |