Haemophilia A is an inherited deficiency in the clotting factor VIII (FVIII), which results in poor clotting following minor trauma and uncontrolled, spontaneous bleeding.
Replacement therapy is the current standard-of-care treatment for haemophilia A, and it relies on prophylactic or on-demand intravenous infusions of clotting factors to replace the missing or deficient levels of FVIII, in order to prevent or control bleeding episodes and long-term joint damage.
Haemophilia A treatment
Though now representing only 8% of the pipeline, plasma-derived FVIII concentrates were the earlier factor replacement therapies. There has been a gradual shift towards recombinant FVIII (rFVIII) replacement therapies over time, which continue to dominate the pipeline (46%).
Although these therapies are effective, they are associated with a great treatment burden, due for example to intravenous administration, the frequency of prophylactic infusions, and the risk of developing neutralizing antibodies, or inhibitors, against replacement factors. The clinical development pipeline indicates that the promise of alternative coagulation promoters (ACPs), such as gene therapies (27%), anti-tissue factor pathway inhibitor (TFPI) monoclonal antibodies (15%), and antisense RNA interference oligonucleotides (4%), to target these areas of significant unmet need is becoming a reality.
Approved in the US in 2017 and Europe, Japan, and China in 2018, Roche’s bispecific antibody Hemlibra (emicizumab) took the first-to-market advantage as the only ACP addressing the unmet needs of frequency, type of administration, and effective treatments for patients with inhibitors. Reporting sales of $229 million in 2018, Hemlibra indicates that the success and curative potential of ACPs in haemophilia A are huge. Many ACPs are entering the late stages of clinical development in haemophilia A, and gene therapies, such as BioMarin’s ValRox (valoctocogene roxaparvovec; BMN-270) and Spark Therapeutics’ SPK-8011, are very close to approval, with ValRox aiming to launch as early as 2020, following an FDA accelerated approval.
Clinical development pipeline for Haemophilia A, 2019
Figure 1: Clinical development pipeline for haemophilia A, 2019
GlobalData. Hemophilia A and B –Epidemiology Forecast to 2028, to be published 2019
GlobalData. Hemophilia A and B – Global Drug Forecast and Market Analysis to 2028, to be published 2019