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Encouraging data for ThromboGenics and BioInvent product

pharmafile | May 7, 2010 | News story | | BioInvent, Lovenox, ThromboGenics, VTE

An antibody-based drug to prevent blood clots after orthopaedic surgery has shown promising results in phase II.

TB-402 is a novel, long acting anticoagulant single injection for venous thromboembolism (VTE) and is being co-developed by Belgium-based ThromboGenics and Sweden’s BioInvent.

The phase II results suggest that TB-402 is better at preventing blood clots than the current standard treatment, Sanofi-Aventis’ Lovenox (enoxaparin), and has comparable safety. TB-402 is also more convenient for the patient, as only one post-surgery infusion is required, compared to daily injections of Lovenox for at least 10 days.

The primary efficacy endpoint of the trial was based on occurrences of VTE in patients 7-11 days after surgery, whether they were symptomatic or asymptomatic. The primary safety endpoint was the number of patients with major or clinically relevant non-major bleeding from randomisation until the end of the study at three months. The study enrolled a total of 316 patients across 30 centres in Europe.

For the pooled TB-402 treated group, 47 out of 218 (or 22%) patients experienced VTE; for the enoxaparin treated group, 30 out of 77 (or 39%) patients experienced VTE (p<0.05). The superior reduction was statistically significant, and the study also showed TB-402 and enoxaparin had a similar safety profile.

The companies welcomed the news, and said it would help them to secure a deal with a major pharmaceutical company to co-develop and market the drug.

Svein Mathisen, chief executive of BioInvent, said: “We are delighted with the progress of TB-402 and are excited about the product’s demonstrated success over current treatments in preventing VTE in post-operative patients and the associated advantages of this being delivered as a single dose.”

Patrik De Haes, chief executive of ThromboGenics, commented: “These results also reinforce our confidence that we can secure a significant partnership deal that will allow us to bring TB-402 to market and deliver its significant potential.”

The companies hope that TB-402 could become a widely used treatment in the anticoagulant market, which is set to develop greatly in the next few years, with numerous new products being developed.

Two new oral treatments, Boeheringer Ingelheim’s Pradaxa and Bayer’s Xarelto have already been launched in Europe, and have been tipped to transform the market. Neither drug has yet been approved in the US, however, with some questions remaining about their safety, which could allow other new products to gain market share.

TB-402 is a recombinant human monoclonal antibody that partially inhibits Factor VIII, a key component of the coagulation cascade. Its novel mode of action is expected to reduce the risk of undesirable bleeding events, even at high doses, as well as the need for patient monitoring, the two main drawbacks of current anticoagulant therapy.

Andrew McConaghie