BioInvent International AB and co-development partner ThromboGenics NV announce that the first patient has been dosed in a phase IIb trial with their novel long-acting anticoagulant TB-402 (Anti-Factor VIII) for the prophylaxis of Venous Thromboembolism (VTE) after total hip surgery.

The phase IIb study is a multi-centre, double blind, randomised controlled trial. It is comparing the safety and efficacy of two dose levels of TB-402, given as a single intravenous infusion after hip surgery, with the recently approved factor Xa inhibitor rivaroxaban. The trial will enrol 600 patients across 41 centres in Europe. Results are expected in the second half of 2012.

TB-402 is a recombinant human monoclonal antibody that has a novel mode of action. It targets factor VIII, a key component of the coagulation cascade. An important benefit of TB-402 is that a single injection could provide a stable, long-acting anti-thrombotic effect, for the prophylaxis of VTE after orthopaedic surgery, which is expected to lead to reduced nursing time and improved patient compliance.

Importantly, TB-402's anti-coagulant activity is easily reversible using Factor VIII, in case of bleeding or need for surgery. In contrast, certain newer anticoagulant therapies lack an antidote which can make it difficult to manage serious bleeds or which may complicate or delay acute surgical procedures.

In 2010, TB-402 reported positive results in a 315-patient phase IIa trial for VTE prophylaxis after knee replacement surgery, compared with enoxaparin, the standard treatment for preventing VTE in this setting. The positive pooled results of three doses of TB-402 (0.3 mg/kg, 0.6 mg/kg and 1.2 mg/kg) showed a 22% incidence of total VTE compared with 39% for enoxaparin (p<0.05). In addition, TB-402 was generally well tolerated and demonstrated comparable safety to enoxaparin. The results were published in the Journal of Thrombosis and Haemostasis in February 2011.

Svein Mathisen, CEO of BioInvent commented, “We are delighted about the product's demonstrated success in earlier trials and believe that it represents an innovative approach to the prevention of VTE after hip orthopaedic surgery. TB-402 promises to become a very important entrant into the anticoagulant market where the product would fill a significant unmet need.”

Dr Patrik De Haes, CEO of ThromboGenics, added, “TB-402 has already shown the potential to significantly improve the treatment of VTE in the post-surgery setting. We hope that this study will confirm these promising results and give us a better understanding of the overall benefits that TB-402 can provide to this patient group. We believe that VTE prophylaxis with a single dose of TB-402 that lasts for several weeks is a simple and attractive option for physicians and patients when compared with other anticoagulant regimes that are currently available.”

TB-402 has the potential to be an important new entrant into the anticoagulant market. It is a long-acting agent, which means it could be given as a single dose to prevent the development of VTE in patients undergoing surgery. This simple approach to prophylaxis would be an attractive option, as all current anticoagulant treatment options require daily treatment for up to several weeks. Importantly, this could lead to better patient compliance.

TB-402 is a recombinant human monoclonal antibody that partially inhibits factor VIII, a key component of the coagulation cascade. This novel mode of action is expected to reduce the risk of undesirable bleeding events, as well as the need for anticoagulation monitoring. These are the two main drawbacks associated with current anticoagulant therapy.

VTE is the third most common cardiovascular disease after myocardial infarction and stroke. It includes both Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE). DVT is caused when a blood clot forms in a deep vein, most commonly in the deep veins of the lower leg. PE occurs when a blood clot blocks the main artery of the lung or one of its branches. DVT and PE are major public health issues. It is estimated that in the US alone, more than 600,000 patients are treated for venous thromboembolisms such as DVT or PE each year. Moreover, DVT and PE together may be responsible for more than 100,000 deaths in the US each year.

BioInvent International AB, is a research-based pharmaceutical company that focuses on developing antibody drugs.

ThromboGenics is a biopharmaceutical company focused on the discovery and development of innovative medicines for the treatment of eye disease, vascular disease and cancer.