No “clear and consistent evidence” of difference in inhibitor risk
There is no clear and consistent evidence of a difference in the incidence of inhibitor development between factor VIII products derived from plasma and those made by recombinant DNA technology.
The Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency has now completed its review of factor VIII medicines to evaluate the risk of developing inhibitors in patients with haemophilia A who have not previously been treated with these products.
The review was started following publication of the SIPPET study, in which inhibitors were found to develop more frequently in patients receiving recombinant factor VIII products than in those receiving plasma-derived factor VIII products.
The PRAC review also considered other relevant studies, including interventional clinical trials and observational studies. Although these differed in their design, patient populations and findings, the PRAC concluded that they did not provide clear evidence of a difference in the risk of inhibitor development between the two classes of factor VIII medicines.
It recommended that product prescribing information should be updated to list development of inhibitors as a very common side effect in previously untreated patients and as an uncommon side effect in previously treated patients. In addition, the existing warning on inhibitor development should be amended to highlight that the presence of low levels of inhibitors poses less of a risk of severe bleeding than high levels.
Given the different characteristics of individual products within the two classes, the PRAC considered that evaluation of the risk of inhibitor development should be at the product level and not at the class level. As a result, the risk for each individual product will continue to be assessed as more evidence becomes available.
But what will those assessments mean for patients in the UK?
The European Medicines Agency regulates medicines within the EU and the European Court of Justice adjudicates appeals against its decisions. Prime Minister Theresa May has said that post-Brexit the UK will no longer be subject to ECJ decisions. So it is almost certain that the EMA will relocate, with Germany, Italy, the Netherlands, Ireland, Sweden, Austria, Denmark and Spain all bidding for it.
International collaboration is crucial in the important in the development and monitoring of drugs for rare diseases. Let’s hope that the international links developed within the haemophilia community over the recent decades do not fall foul of the increasingly hostile exchanges between London and Brussels.