Recombinant factor products haven’t changed much in recent decades. While preventative treatment (prophylaxis) revolutionised the lives of many people with a bleeding disorder, the typical treatment regime - injections into the vein two or three times each week - places a significant burden on individuals and families.
Now, a flurry of research into new factor products for haemophilia A and B which can be given less often, yet are just as effective at preventing bleeds, is seeing very promising results. Products to treat those with inhibitors are also being researched but still have some way to go. The first of these longer-lasting products have recently been approved by the US licensing authority, the Federal Drugs Administration (FDA), and similar treatments are likely to reach the UK by the end of 2015 or 2016.
Major pharmaceutical companies are conducting intense research, with hundreds of people with haemophilia taking part in each of the numerous clinical trials worldwide.
The research pipeline is centred on three main approaches, known as Fc fusion, PEGylation and albumin fusion (see our glossary for full explanations). All of these are aiming to prolong the ‘half-life’ of clotting factors VIII and IX by altering the structure of the protein molecules so that the body takes longer to clear them from the blood circulation and they therefore work for longer after being injected.
Results seen in clinical trials so far indicate that the new products could mean significantly fewer injections for people receiving prophylaxis for haemophilia B (to every 1-2 weeks), and to around twice weekly for those with haemophilia A. While exact treatment patterns will vary, this would make a huge difference to the lives of many Haemophilia Society members. In trials, the number of spontaneous bleeds has so far stayed the same or dropped compared with existing factor treatments, with no serious side effects evidenced so far.
First to market in the US are Biogen Idec, who, working in partnership with SOBI, have completed clinical trials and been granted FDA approval for two new longer-lasting factors. Both products consist of factor XIII or IX molecules fused with fragments of Fc, a protein found in immunoglobin (antibodies), which makes the treatment last for days or weeks, rather than hours, in the blood circulation. The two products approved are:
- Alprolix BIIB029, a new longer-lasting clotting factor for haemophilia B, (received FDA approval in March 2014)
- Eloctate / BIB031, a longer-lasting treatment for haemophilia A, received FDA approved in June 2014.
Other trials of similar products from other drug manufacturers are well underway, with similarly exciting results so far:
Baxter, Bayer and Novo Nordisk are all working to create new long-lasting factor through a technique called polyethylene glycol conjugation or ‘PEGylation’ of clotting factors – a technique which has been proven to work in medication for other conditions.
Novo Nordisk’s trials are almost complete, with a hemophilia B drug, known for now as ‘N9-GP’likely to receive a US license early next year, and another treatment, ‘N8-G9’, for haemophilia A, in the pipeline.
For haemophilia A, two more PEGYlated factor VIII products are being developed by Baxter (currently known as ‘BAX-385’) and Bayer (working name ‘BAY 94-9027’).
Finally, CSL Behring are developing a longer-lasting product for haemophilia A treatment, (‘CSL654’) using the third technique in current use, albumin fusion. Albumin is a protein that occurs naturally in the blood and so is highly unlikely to stimulate an immune system response. Trials have showed far fewer does of factor needed in haemophilia B treatment when albumin is linked with recombinant factor IX.
If all continues to progress well, we can expect to see the first of these products made available in the UK in 2015 and 2016.
While new treatments may come with a higher upfront price tag - at least initially - many clinicians are already taking the view that more effective preventative treatment will save hospital costs in treating bleeds, and the wider choice of products from competing pharmaceutical companies will make treatment cheaper overall in the medium to long-term.