Brian O’Mahony
Chief Executive, Irish Haemophilia Society
Innovation in haemophilia treatment has increased exponentially in recent years with new approaches, new therapies and several ongoing clinical trials.
Since the 1970s, the standard therapies for haemophilia were intravenous injections of the missing clotting factor — factor VIII (FVIII) for haemophilia A and factor IX (FIX) for haemophilia B. These were typically infused two to three times per week to maintain a base or trough factor level and prevent most spontaneous bleeding. In Ireland, since the late 1990s, these were recombinant or synthetic products.
Progression of haemophilia therapies
In 2014, a new generation of extended half-life recombinant factor concentrates became available. This allowed for less frequent infusion or greater protection (or both, in FIX cases). For individuals with severe FVIII deficiency, treatment was required twice weekly. In FIX deficiency, treatment was required once per week or even once every two weeks due to the longer half-life of the infused FIX in the body.
In the last year, the first licensed gene therapies for both FVIII and FIX deficiencies were introduced.
Subcutaneous therapies
Novel approaches targeted the other side of the coagulation cascade. Instead of merely replacing the missing factor through infusion, a new category of therapies emerged, known as rebalancing agents. They are subcutaneous therapies aiming to inhibit or reduce the impact of naturally occurring anticoagulants, such as antithrombin, anti-tissue factor pathway inhibitor (TFPI) or protein C. These therapies allow the blood to clot as required.
Several such products are currently in advanced stages of clinical trials; one is already licensed in Canada for some indications. The first FVIII mimetic was licensed in 2018 and is now widely used in Ireland. This is a subcutaneous therapy, which can be used weekly or every two to four weeks.
Gene therapies for haemophilia
In the last year, the first licensed gene therapies for both FVIII and FIX deficiencies were introduced. These new therapies use an adeno-associated virus (AAV) vector to deliver a FVIII or modified FIX gene to the liver where the liver cells start producing FVIII or FIX, respectively. The durability of these therapies is unknown but postulated to be at least five to seven years for FVIII and at least 10 years for FIX. These therapies have been a positive step forward for haemophilia patients.