Professor John Pasi
Professor of Haemostasis and Thrombosis, Barts and the London School of Medicine and Dentistry, London
Treatment for haemophilia is undergoing a rapid and transformational change thanks to the application of breakthroughs in both science and biotechnology.
Without treatment, men and boys with severe haemophilia will bleed, without any injury, repeatedly into joints and muscles, leading to a progressive and disabling arthritis at an early age. To prevent this, state-of-the-art treatment involves intravenously injecting the missing clotting factor every alternate day. Although effective, this is far from perfect and alternate day injections are a huge treatment burden, especially in young boys. For the last 30 years this has been our best treatment option.
Decade of innovation to improve clotting factors
Over the last decade there has been an explosion of innovation targeting haemophilia. Using bioengineering we now have modified clotting factors to last significantly longer in the circulation, enabling the number of injections needed to be significantly reduced, level of clotting factors to be kept higher and protection against bleeding to be improved. This was the first major step forward both reducing the burden of treatment and improving care for patients. Another next generation of such ‘super’ factors is now just around the corner.
We all must look to how we can address the inevitable substantial costs of these therapies in order to make them available to our patients.
New haemophilia treatments require less frequent injections
But that has not been the only development in the field. Science has looked to develop alternative ways to prevent bleeding in haemophilia. Such approaches include mimicking clotting factors with engineered antibodies or suppressing inhibitors of coagulation to rebalance the abnormal clotting using antibodies, specific novel bioengineered proteins or small RNA molecules. All these approaches can be given by simple subcutaneous injection infrequently (weekly to monthly), so dramatically reducing the burden of traditional intravenous treatment. Already available in many countries, the first of this class of treatment is transforming lives.
The promise of gene therapy
For years, haemophilia was seen as an ideal target for gene therapy and the ‘Holy Grail’ for treatment – a single gene disorder, a clear ‘cause and effect’ relationship, where only a small amount of clotting factor will make a huge difference to patients’ lives. Gene therapy in haemophilia, though, for years has been littered with a series of failures.
However, use of a tiny adeno-associated virus (AAV) to transfer genes to the liver, has been remarkably successful and allowed haemophilia treaters to be increasingly optimistic that gene therapy will work for haemophilia. Data from recent studies are fantastically encouraging, with levels of clotting factor way above the improvements initially hoped for, leading to markedly reduced bleeding and a massively reduced need for treatment.
The next challenges are cost-related
There remain a number of scientific and clinical questions surrounding the use of these new treatments and gene therapy that we need to address. Aside from the science, a considerable unanswered question remains – cost.
These treatments will be expensive – especially gene therapy, which has the potential to last for years, if not a lifetime. With haemophilia treatment entering a golden era, we all must look to how we can address the inevitable substantial costs of these therapies in order to make them available to our patients.