TB-402
Product description
TB-402 is a human monoclonal antibody that targets Factor
VIII, a blood clotting factor. The product is being developed as an
anti-coagulant, to prevent deep vein thrombosis in connection with
orthopaedic surgery and to prevent stroke in patients with atrial
fibrillation.
Product rationale
TB-402 shows an advantageous partial inhibition of Factor
VIII, and the level of inhibition does not rise beyond a particular
point, regardless of the dose administered. This and other evidence
suggests that TB-402 could have a lower risk of overdose and fewer
side effects than currently available anti-coagulants. As a
consequence patients may require less monitoring.
In addition, TB-402 could be more convenient to administer than current treatments. Its long half life means that it could be given to patients less frequently than other anti-coagulants.
Clinical status
A Phase II proof of concept study was reported in May
2010, in which TB-402 demonstrated superior and statistically
significant antithrombotic activity to enoxaparin. The study was a
multicenter, dose-escalating, randomised, open-label trial,
evaluating TB-402 against enoxaparin for the prophylaxis of VTE
after knee surgery. 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 study also showed that TB-402 and enoxaparin had a similar
safety profile.
Phase I studies with TB-402 have further been completed. One randomised, placebo-controlled, dose-escalation study in 56 healthy male volunteers showed that the drug was safe and well-tolerated. No serious adverse events or bleeding complications were reported. In addition the drug showed anti-coagulant effects.
A further Phase I study showed that the activity of TB-402 can be reversed by administering recombinant Factor VIII. It also showed that the product did not interact with either warfarin or Low Molecular Weight Heparin, the most commonly prescribed anti-coagulants.
Preclinical studies in animal models demonstrated that TB-402 could inhibit thombosis without causing increased bleeding.
Development and commercialisation strategy
TB-402 is being developed in conjunction with
ThromboGenics Ltd.