Takeda Pharmaceutical Company Limited (TSE: 4502/NYSE:TAK) ("Takeda") today announced the results of a phase 3 trial investigating the efficacy and safety of recombinant von Willebrand factor (rVWF) prophylaxis,1 one of the 12 abstracts being presented at the International Society on Thrombosis and Haemostasis (ISTH) Virtual Congress 2021. Several of these abstracts explored the use of prophylaxis as part of Takeda's commitment to improving outcomes for patients with rare bleeding disorders.

The prospective, phase 3, open-label, international multicenter study included 23 patients with severe von Willebrand disease (VWD). The study period was 12 months and included two arms; the prior on-demand (OD) group included patients previously taking OD VWF and the switch group included patients previously taking prophylactic plasma-derived von Willebrand factor (pdVWF) treatment [LPB0128]. Results showed that prophylaxis with rVWF effectively reduced spontaneous, treated annualized bleeding rates (sABRs) in patients previously treated OD, and the same level of hemostatic control was maintained in patients who switched from prophylaxis with pdVWF. The sABR was reduced by 91.5% on study (while receiving prophylactic rVWF) compared with historical sABR in prior OD patients, and sABR was maintained on-study in switch patients (sABR on-study: historical ratio (95% CI): 0.09 (0.02, 0.35) in prior OD arm; 0.55 (0.09, 3.52) in switch arm). No new risks were identified, with no serious adverse events related to rVWF reported.1The pharmacokinetics (PK) of VWF:ristocetin cofactor (VWF:RCo) and FVIII pharmacodynamics (PD) [PB0917] were also studied and presented at the congress.2

"Stopping a bleed in VWD does not prevent subsequent bleeds, and the complications and unpredictable nature of these bleeds for many OD treated patients can impact their daily life," commented Dr. Flora Peyvandi, Director of the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore, Policlinico, University of Milan, Italy. "These exciting phase 3 results are important in improving understanding about the potential benefit of prophylaxis with rVWF and what this may offer patients with VWD in reducing spontaneous bleeds in the future."

A literature review being presented at ISTH 2021 also studied the rates of bleeding-related complications, quality of life and healthcare resource utilization in VWD [PB0924].3 Data gathered from a further retrospective cohort study investigating the characteristics and management of patients with VWD in UK general practice discussed the occurrence of bleeding events in patients with a mild disease status [PB0927].4

Additional investigational data across Takeda's hematology portfolio assessed the efficacy and safety of PK-guided prophylaxis in patients with hemophilia A. Results from the real-world German AHEAD study, which aims to examine long-term effectiveness and safety of antihemophilic factor (recombinant), rAHF (ADVATE),5help to provide an understanding of the bleeding rates in patients with hemophilia A receiving PK-guided prophylaxis versus standard prophylaxis [PB0509].6 PK-guided prophylaxis was further studied in another real-world analysis using data from the CHESS II database to assess the impact on clinical and health resource utilization outcomes [PB0554].7 Data from a post hoc analysis of the PROPEL phase 3 study on the effects of PK-guided prophylaxis targeting specific FVIII trough levels with rurioctocog alfa pegol (ADYNOVATE) were also presented at the congress [PB0542].8

"At Takeda we are committed to helping make a difference to the lives of patients with rare hematological disorders, both today through our broad portfolio of treatments, and in the future by developing innovative solutions to address unmet needs," commented Wolfhard Erdlenbruch, MD, Head, Global Medical Affairs Hematology. "The data presented at ISTH 2021 highlights the potential for rVWF to address unmet needs in VWD, as well as helping us to understand the clinical and resource utilization impact when individualizing treatment through PK-guided prophylaxis in hemophilia."

Also featured at the congress was the phase 3 study design exploring TAK-755, an investigational recombinant ADAMTS13 replacement therapy being studied for use as prophylactic and OD treatment for patients with severe congenital thrombotic thrombocytopenic purpura (cTTP) [PB0837],9 and an abstract which reviewed the clinical burden of TTP [PB0843].10 Improving awareness and understanding around this rare and life-threatening blood disorder associated with ADAMTS13 deficiency,9together with the development of TAK-755, forms part of Takeda's commitment to invest in research that has the potential to transform the future care of even more patients affected by rare hematological disorders.

About the Phase 3 Recombinant von Willebrand Factor Study 

In the prior OD group, subjects initiated rVWF prophylactic treatment with twice-weekly infusions of 50±10 IU/kg per infusion. In the switch group, subjects initiated rVWF prophylactic treatment based on matching (±10%) the weekly dose of their prior pdVWF prophylaxis regimen.

23 enrolled patients received rVWF prophylaxis (prior OD arm: n=13; switch arm: n=10) and 18/23 (78.3%) patients had type 3 VWD. Over the 12-month study period, 11/13 (84.6%) prior OD patients and 7/10 (70.0%) switch patients had a treated, sABR of zero, whereas, historically, 13/13 prior OD and 1/10 switch patients had an sABR >2. Benefit-risk profile was maintained, with no newly identified risks. One adverse event, a headache of moderate severity, was considered possibly related to rVWF by the investigator and led to discontinuation of rVWF and study withdrawal.

About von Willebrand Disease (VWD) 

VWD is the most common inherited bleeding disorder, affecting up to one percent of the U.S. population.11 VWD is caused by a deficiency or dysfunction of VWF, one of several types of proteins in the blood that are needed to facilitate proper blood clotting.11 Due to this defect or deficiency in VWF, blood is not able to clot effectively in people with VWD, resulting in prolonged bleeding.11 There is a broad spectrum of disease severity, however, severe bleeding can occur in anyone living with VWD.12

About Hemophilia 

Hemophilia is a chronic disease that causes longer-than-normal bleeding due to absent or deficient clotting factor in the blood.13 Hemophilia A is more common than hemophilia B; in 2018, hemophilia A affected about 173,711 people, whereas hemophilia B affected about 34,289 people worldwide.14

People with hemophilia, working closely with their healthcare professionals, can live healthy lives with proper care and adequate treatment.15 Treatment regimens typically include on-demand and/or regular prophylactic infusions of factor replacement therapy to control or prevent the risk of bleeding.16

About Takeda Hematology 

Following its recent acquisition of Shire, Takeda is a leader in hemophilia with the longest heritage and market-leading portfolio, backed by established safety and efficacy profiles with decades of real-world experience. We have 70+ years driving innovation for patients17 and a broad portfolio of 11 products across multiple bleeding disorders.18 Our experience as a leader in hematology means we are well prepared to meet today's needs as we pursue future developments in the care of blood disorders. Together with the hematology community, we are raising expectations for the future, including earlier diagnosis, earlier and full protection against bleeds, and more personalized patient care.