Haemophilia is an X-linked genetic disease associated with the dysfunction of the biological cascade leading to blood clotting. Coagulation factors are vital to the functioning of the mechanism that the human body uses to protect and repair itself from physical injury, by the formation of blood clots to seal ruptured blood vessels. Haemophilia patients have a reduced capacity to stop bleeding and are prone to bleeding internally, into joints and organs, and often require hospitalisation 3-4 times per year. Without proper treatment, haemophiliacs typically die from organ failure in their teens.
Haemophilia A is treated with replacement therapy of a human blood protein, Factor VIII.
Gram for gram this is probably one of the most expensive compounds in the world and consequently an expensive treatment. It sells for up to $4m per gram. Many patients, therefore, can simply not afford the treatment.
But there is also a real shortage in the supply of Factor VIII.
World Federation for Hemophilia (WFH) annual reports suggest that there is an annual supply of ~8BN International Units (IU) of both recombinant (manufactured) and plasma derived (collected and processed) Factor VIII. In the developed countries of the world, patients, on average, get around 100,000 IUs per year. That’s enough to treat 80,000 patients.
The WFH report 151,000 patients under treatment (2014). But the WHO estimates the patient population at over 500,000.
Haemophilia B is treated with Factor IX. The statistics indicate the same problem. It’s expensive and there just isn’t enough to go around.
Blood Products and the Advent of Recombinants
Clotting factors were unavailable before the 1960s. From then, until the early 1980’s, they were supplied only from processed human blood plasma (fractionation). The infection of 75% of the world’s haemophiliac population with HIV, however, caused a significant review of blood product production processes, and aided the introduction of the recombinant products. More recently, concerns over the transmission of variant Creutsfeld Jacob Disease (vCJD) and Hepatitis C virus have further led to a greater demand for the recombinant versions.
Fractionation, the process of extracting the various components of human plasma, including the clotting factors, was already an expensive process. The added requirement of monoclonal antibody purification simply served to increase the cost and support the high prices charged for the recombinant products. Despite these premium prices, recombinant products have ~80% of the market in the industrialised nations. Plasma derived product is still used; though supply in Europe is now sourced principally from the USA where there is a perceived reduced risk from vCJD. Fractionation from human plasma, however, continues to be limited due to limited blood and plasma donations.
Blood products were always subject to significant government control, particularly in Europe where fractionation plants were often operated as government agencies. The introduction of recombinant products served to fill the gap left by the reduction in supply caused by the increased purity demands on blood-derived product. With patient pressure on the FDA to approve, and patent protection, the recombinant products rapidly gained market share and the markets remain remarkably free of competing manufacturers.