1.2. Treatments for Haemophilia
The current ‘gold-standard’ treatment for haemophilia is prophylactic
factor replacement therapy, intravenous injection of factor VIII/XI
concentrates. There are many preparations available in Europe (Table 2).
Prophylaxis is used with the aim of rising FVIII and FIX activity above
a level that is detectable (>1%) to prevent bleeding and
reduce or delay the incidence of joint disease. The short biological
half-lives of FVIII and FIX proteins require frequent infusions, three
times a week (haemophilia A) or twice a week (haemophilia B) [8]. A
major complication of factor replacement therapy is the formation of
inhibitory antibodies against the coagulation factors, rendering these
ineffective [9].
Inhibitors develop in approximately 25% to 30% of haemophilia A
patients and, less frequently, in 3% to 5% of haemophilia B patients.
Treatment with bypassing agents (BPAs) and immune tolerance induction
(ITI) is required in such patients to eradicate inhibitors, nonetheless
patients continue to exhibit increased morbidity and mortality
[9-10]. In non-inhibitor patients, prophylaxis can decrease the
frequency of bleeding and slow the progression of joint disease, thus
improving the quality of life. However, studies have shown that bleeding
events are not eliminated for all patients, and joint disease still
appears in young adults [11-12].
The mainstay for treatment of bleeding episodes in patients with
high-responding inhibitors is the so-called ‘by-passing agents’,
recombinant FVIIa and anti-inhibitor coagulant complex (FEIBA). In
patients with inhibitors to FIX, prophylaxis with FIX products is not
possible.
Several challenges and unmet needs remain in the treatment of
haemophilia, since patients continue to experience breakthrough
bleedings, progressive joint disease, and high rate of inhibitor
development. These numerous challenges can be addressed by emerging
technologies such as gene replacement therapies (advanced therapy
medicinal products or ATMPs).