BioInvent International AB and co-development partner ThromboGenics NV announce the results from a Phase 2b trial comparing TB-402, a long acting anticoagulant, against rivaroxaban, 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 Phase 2b 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. Rivaroxaban is a recently approved oral factor Xa inhibitor for the prevention of VTE after elective hip or knee 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.
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.
Svein Mathisen, CEO of BioInvent, commented, “In our collaboration with ThromboGenics we decided to raise the bar for TB-402 by pitching it in a head-to-head trial against Xarelto. Investment decisions should be based on business context and solid science. In this disappointment it is comforting to know that we did get a clear answer. As we face a number of important data points later this summer both in our collaboration with Genentech as well as in the study of our proprietary multiple myeloma drug it is this principle which guides us.’’
Dr. Patrik De Haes, CEO of ThromboGenics, also commented, “The decision to conduct this study comparing TB-402 with a potential future market leader, rivaroxaban, has been validated. The result, while disappointing, means that we do not need to invest any further in the development of TB-402. We intend to utilize our resources to support the commercialization of our lead product ocriplasmin and to develop our ophthalmology pipeline.”