A year on from my last analysis of the World Federation for Hemophilia (WFH) Report on the Annual Survey we see in 2019 a further improvement in the number of people treated. However, we also see new data on the prevalence of the haemophilia A which suggests there are even more patients not getting treated.

The WFH Annual report on the 2019 Global Survey published new data on the estimated global Haemophilia population based on recent research in the area. 

The global haemophilia A population has previously been estimated at around 400,000 with an incidence at birth of 1 in 5,000 males. The revised prevalence at birth was estimated from the FranceCoag data and confirmed with data from the United Kingdom and Canadian registries. This novel approach estimates the prevalence at birth is now 1 in 4,000 males around 40% of which are classified as severe.

The WFH now estimate a global haemophilia population (A & B) of 794,000. Assuming Haemophilia A is still five times more prevalent than B (deficiency in Factor IX), this suggests a global Haemophilia A population of 660,000

As previously explained, the WFH data not altogether complete with some countries not fully reporting number of patients or number of International Units (IUs) used. But by extrapolating the data based on our experience of the data over the last ten years we estimate that, in 2019, more patients are now receiving treatment (191,000 – 2019; 173,000 – 2018; 161,000 – 2017; just 54,000 in 1999 the first WFH Annual Survey). It is still clear, however, that many are still receiving inadequate treatment based on the number of IUs per patient used.

Based on a prevalence, Slovak Republic, New Zealand, France, Macedonia, United Kingdom, Slovenia, Ireland, Azerbaijan and Iceland have 100% diagnosis – statistically in proportion with their populations or, indeed, their “fair share” of HA sufferers. Another 16 countries all have more than 80% of their “fair share”.

Interestingly in applying prevalence, this suggests that the USA and Germany count only 47% and 50% respectively by prevalence. Nevertheless, we understand treatment generally in the Western World is adequate but wonder if there are haemophiliacs in the USA who, for example, without insurance, don’t get treatment.

Our estimate for 2019 was that there were 9.1BN IUs of recombinant Factor VIII (rhFVIII) and 3.5BN IUs of plasma-derived (pdFVIII) used; a total of some 12.6BN IUs. Since 2011, plasma derived product availability has consistently been in the order of 3-4BN IUs per annum. Over the same period, our estimated recombinant product volume has increased in availability though the 8% growth in 2018 was not apparent in 2019 (a reduction of ~800M IUs). The introduction of Hemlibra by Roche, a novel bispecific antibody, has clearly impacted sales of human FVIII particularly in the Western World.

Nevertheless, we believe that this analysis continues to demonstrate the rigid nature of FVIII production: for pdFVIII by the quantity of plasma donated and fractionated; and for rhFVIII by the installed capacity of production.

Using the WFH data we’ve calculated the average usage per patient with estimated average consumption of IUs per patient in the triad at ~150,000 at a cost, on average, of almost $100,000 per year. For the patients in the USA this is probably more than $150,000 due to higher prices. In the countries outside the triad, i.e other than USA, Japan, Western Europe, the average usage per patient is less than 50,000 IUs. 

It’s important to understand that dosing of patients is based on their weight and the severity of the condition with children clearly needing less than a full grown adult. For example, an infant on prophylaxis (to prevent bleeding) would need ~ 40,000 IUs per year and an adult as much as 300,000 IUs. “On demand” treatment (on the occurrence of a bleed) needs much less – 4,500 and 36,000 respectively. Prophylaxis is the standard of treatment in the western world. 

Assuming an average 100,000 IUs per annum, the 2019 9.1BN IUs world production of recombinant Factor VIII could treat about 90,000 patients – ~50% of the estimated 191,000 patients. The low usage outside the triad continues to show the inadequacy of treatment in most of the world not forgetting those getting no treatment at all – potentially 469,000 patients.

If all 191,000 patients were to get 100,000 IUs per year, we would need 19BN IUs – another 10BN IUs – that means more than doubling existing recombinant production.

If all 660,000 patients were to get on average just 50,000 IUs per year, we would need 33BN IUs – another 24BN IUs – that’s almost tripling existing recombinant production.

As previously reported, 2019 again saw just eight countries (United States, Japan, Brazil, United Kingdom, France, Germany, Russia, Italy and Canada) consume more than 60% of the total available FVIII. And a total of just 14 countries, representing 19% of the world population and 39% of the patients, consumed 80% of the rhFVIII. The WFH survey covers 139 countries.

We still get asked why the current producers don’t just increase production? Well, they have, but with more expensive “improved” versions. And even with the new entrants, there still isn’t enough to go around. With our low-cost production process, we intend to focus on markets currently unserved and get more patients treated.