Preclinical testing in animal models has shown that the new therapy greatly reduces the risk of thrombosis (unwanted clotting of the blood inside a blood vessel) without increasing the risk of bleeding, a common problem with most current therapies, which necessitates frequent monitoring.
Assuming the clinical trials go to plan, the drug will enter "a massive market" according to Stuart Laermer, ThromboGenics' chief business officer.
Blood clots are formed by a mechanism known as the coagulation cascade, which involves numerous proteins, including Factor VIII. Sometimes the cascade can go too far and cause unwanted clotting leading to heart attacks, deep vein thrombosis (DVT) and even atrial fibrillation when the blood clot is formed in connection with heart arrhythmia.
Without the use of anticoagulants, as many as 80 per cent of orthopaedic patients would be at risk from heart attacks and DVT.
One of the major problems with using anticoagulants is that they can cause spontaneous bleeding, with patients needing frequent check-ups. While there are oral anticoagulants such as warfarin (coumadin), on the market, many anticoagulants, such as heparin and low molecular weight heparin need to be administered by daily injection, and complications can exist for those patients on more than one drug. Compliance is often an issue for patients on anticoagulants and a once a month treatment would vastly improve this.
The antibody was isolated from patients suffering with haemophilia (a genetic illness that impairs the patients ability to form blood clots) who were treated with recombinant Factor VIII. In unusual cases, patients form antibodies, such as TB-402 against the recombinant Factor VIII.
"TB-402 is a human monoclonal antibody which only partially inhibits Factor VIII, in preclinical models we found that no matter how much TB-402 is given, only about 40 per cent of the Factor VIII is blocked," Steve Pakola, MD, chief medical officer at Thrombogenics told DrugResearcher.com.
This is crucial to efficacy of the drug, as only unwanted clotting is prevented, minimising the risks of unwanted bleeding that can lead to haemorrhagic strokes if too much of an anticoagulant is administered.According to Pakola, preclinical data indicates that the therapy has an excellent safety profile and has a half-life of more than several weeks, which should allow dosing once a month, which would fit in nicely with the monitoring that joint replacement patients receive, the most common sufferers of thrombosis.
The Phase I trial will be a typical study looking at evaluating the safety of the therapy starting off with low doses and then looking at how high a dose you can go to before observing any safety problems.
The planned Phase IIa study will look into the prevention of DVT in orthopaedic surgery patients who have just undergone hip or knee replacement treatments.
Pakola continued: "There is a lot of literature out there specifying the risks of DVT in joint replacement patients and that makes it a good place to start in the initial evaluation and proof of concept."
"The question we want to answer is can we cure the DVT with a single shot of the drug."
The company is hoping that the anticoagulant will also be indicated as a treatment for atrial fibrillation when the blood clot is formed in connection with heart arrhythmia, where clots develop in the heart before breaking off and entering the brain leading to strokes.