Extended (or enhanced) half-life factor concentrates
For people with haemophilia, the use of recombinant (laboratory made) factor products hasn’t changed much in recent years. While preventative treatment (prophylaxis) has revolutionised the lives of many people with a bleeding disorder, the typical treatment regime – regular injections into a vein at least twice a week – can place a significant burden on individuals and families.
Now, a flurry of research has resulted in new factor products for haemophilia A and B becoming available in the UK. You can inject these less often, but they work just as well in preventing bleeds. In trials, patients were able to inject once or twice a week for haemophilia A and every one or two weeks for haemophilia B. Overall, they had fewer or the same number of spontaneous bleeds and no serious side effects.
Treatment patterns are worked out individually, depending on your own treatment response and bleeding pattern, but these drugs are likely to make a difference to the lives of many Haemophilia Society members. It’s likely that treatments may be used slightly differently in everyday practice to how they were prescribed in the trials, but overall we would expect many to have a reduction in frequency of treatment.
The first of these longer-lasting products have now been approved for use in the UK and more are in the pipeline. All of them aim to increase the time that the body takes to remove the factor from the bloodstream. This means they work for longer after being injected. The researchers call this increasing the ‘half-life’ – the amount of time it takes the level of the drug in the bloodstream to reduce by half – so these drugs are collectively known as ‘extended half-life’ or EHL treatments. There are three main ways of producing these drugs: Fc fusion, PEGylation and albumin fusion.
This is a technology that has been around for about 15 years. It’s been used to produce arthritis drugs safely for some years now. To make haemophilia treatment, each single molecule of factor is joined (fused) to the Fc part of a human antibody protein. The Fc part of the antibody stops the fusion protein being broken down inside body cells. Instead, it’s pumped back into the bloodstream. This means that overall, the factor and its attached Fc protein can circulate for longer – in the case of factor IX products, for days rather than hours.
The fusion protein is made inside lab-grown human cells. It’s possible that making the protein inside human cells may bring the inhibitor rate down, but these drugs are too new for us to know that for certain.
The first available form of recombinant factor VIII Fc fusion protein is called Elocta, produced by Biogen Idec in collaboration with SOBI. This has now been approved to treat severe haemophilia A in the UK.
Another SOBI product that will be available shortly is Alprolix, which is a recombinant factor IX Fc fusion protein for haemophilia B.
This means attaching a molecule of polyethylene glycol to a drug. In simple terms, this makes it much larger and slows down the rate that the drug is removed from the body. Again, this means it stays in circulation in the blood for longer. This technology has been used for over a decade to make drugs safely for many different medical conditions.
Baxter, Bayer and Novo Nordisk are all working to create new long-lasting factor through PEGylation. Novo Nordisk’s trials are almost complete, with a haemophilia B drug, known for now as ‘N9-GP’ likely to receive a US licence early next year, and another treatment, ‘N8-G9’, for haemophilia A, in the pipeline.
For haemophilia A, Baxter and Bayer each have PEGylated factor VIII products in development (currently known as ‘BAX-385’ and working name ‘BAY 94-9027’).
This means that a naturally occurring human blood protein (albumin) or a laboratory-made (recombinant) copy of albumin is joined to the factor molecule. The albumin also slows down the rate at which the factor is removed from the blood, so it circulates for longer. These drugs are too new for us to know any long-term effects, but the use of a natural human protein is unlikely to increase the risk of inhibitors forming.
CSL Behring has developed a longer-lasting product for haemophilia B using albumin fusion. In trials, patients needed far fewer doses for prophylaxis and this drug, Idelvion, has now been approved for use in the UK.
While these new treatments may appear to be more expensive, the way they are used by patients should mean that overall treatments costs aren’t increased. Being better able to prevent bleeds will save hospital costs in the long run, both immediately after a bleed and in dealing with long-term joint damage. You may also use less factor overall, so costs will hopefully not become a major issue. In one trial, patients used 40% less of the new EHL factor than their previous factor.
You can find out more about the new treatments by downloading our factsheets:
Extended half-life (EHL) factor VIII – PDF
Extended half-life (EHL) factor IX – PDF