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Clinical Trials

Date: 2012-06-05

Type of information:

phase: 2b

Announcement: results

Company: BioInvent (Sweden) ThromboGenics (Belgium)

Product: TB-402 (Anti-Factor VIII)

Action mechanism:

This recombinant human monoclonal antibody partially inhibits Factor VIII, a key component of the coagulation cascade.

Disease:

prophylaxis of venous thromboembolism (VTE) after total hip surgery

Therapeutic area: Cardiovascular diseases

Country: Europe

Trial details: The Phase IIb trial was a multicenter, randomised, double blind trial, evaluating single doses of either 25 or 50 mg TB-402 against rivaroxaban in patients undergoing hip replacement surgery. TB-402 was administered as a single intravenous infusion two to four hours post-operatively, and rivaroxaban was administered as 10 mg once daily for 35 days. A total of 632 patients were enrolled between April and December 2011 in 36 centers across nine countries.
The primary efficacy outcome of the study was the incidence of total VTE up to 35 days post operatively. VTE consisted of both asymptomatic deep vein thrombosis (DVT), as detected by bilateral venography, and symptomatic VTE, i.e. DVT or pulmonary embolism (PE). The principle safety outcome was major bleeding or clinically relevant non-major bleeding events up to 35 days after surgery.

Latest news: * On June 5, 2012, BioInvent International and co-development partner ThromboGenics have announced the results from a Phase IIb trial comparing TB-402, a long acting anticoagulant, against rivaroxaban (Xarelto®; Bayer), an oral anticoagulant.  The study showed that the incidence of venous thromboembolism (VTE) was similar with both drugs but patients receiving TB-402 had a significantly higher incidence of bleeding events.  Based on these results, BioInvent and ThromboGenics have decided to stop further development of TB-402. The study showed that the incidence of VTE was similar for TB-402 and rivaroxaban. In the pooled TB-402 group, 5.3% of patients had VTE, compared with 4.7% in the group treated with rivaroxaban. All incidences were asymptomatic DVT. However, major or clinically relevant non-major bleeding occurred in 6.5% of the patients treated with TB-402 compared to 1.4% of patients treated with rivaroxaban, a statistically significant difference.
ThromboGenics now intends to utilize its resources to support the commercialization of its lead product ocriplasmin and to develop its ophthalmology pipeline. The company has recently resubmitted a BLA with the FDA for ocriplasmin intravitreal injection, 2.5 mg/mL, for the treatment of symptomatic Vitreomacular Adhesion (VMA) including macular hole.

* On June 29,2012, BioInvent has announced that the company has decided to initiate negotiations with trade unions regarding organisational changes. The decision is due to the fact that development of the antithrombotic agent TB 402 has been stopped. The company’s resources will therefore be reprioritised to focus on the continued development of BI 204 for the treatment of acute coronary artery disease and new and existing cancer projects such as BI 505.
The new organisation is planned to have 68 full-time employees compared with the current 89. The reduction in work force and other reprioritisations are expected to result in cost savings of around SEK 15 million on a full-year basis, fully effective from January 2013.

* On December 16, 2011, ThromboGenics and BioInvent International have completed the enrolment of a 632-patient Phase IIb trial with their novel long-acting anticoagulant TB-402 for the prophylaxis of venous thromboembolism (VTE) after total hip surgery. The trial has recruited patients from 36 centers across Europe. It is anticipated that the swift inclusion of patients in the final recruitment phase of the study will allow the Companies to report the outcome in the second quarter of 2012. This is ahead of previous guidance, which was the second half of 2012.

* On April 27, 2011, ThromboGenics and co-development partner BioInvent International have announced that the first patient has been dosed in a Phase IIb trial with their novel long-acting anticoagulant TB-402 for the prophylaxis of venous thromboembolism (VTE) after total hip surgery.
An important benefit of TB-402 is that a single injection could provide a stable, long-acting antithrombotic 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.

Is general: Yes