General Considerations on Clinical Trials of Hemophilia Medicines

Abstract

Hemophilia is an orphan disease associated with deficiency or complete lack of certain blood coagulation factors due to mutation of genes encoding their synthesis. Patients with hemophilia need continuous replacement therapy with coagulation factor products which are produced by recombinant DNA technology or derived from donated blood plasma. The development of new products or improvement of the production process of already authorised medicinal products involve clinical trials that have to include both previously treated and untreated patients of different age groups. The aim of the paper was to perform an analytical review of general hemophilia issues and major requirements for clinical trials of coagulation factor IX products based on the updated documents of the European Medicines Agency. The paper summarises the basic principles of conducting clinical trials of coagulation factor IX products that are submitted for marketing authorisation as “new” products, based on recommendations of Russian and international regulatory documents, including the updated guideline of the European Medicines Agency. It sums up product safety issues associated with undesirable immunogenicity resulting in formation of inhibitors that provoke allergic reactions or reduce the effectiveness of therapy. The harmonisation of the requirements for clinical trials during preparation and updating of documents by Russian manufacturers should be based on the analysis of the experience with hemophilia products and latest scientific achievements in the disease treatment. In that case it will facilitate the introduction of innovative efficacious hemophilia products into clinical practice.

Keywords

• hemophilia
• recombinant factor ix products
• plasma-derived factor ix products
• clinical trial
• efficacy
• safety
• immunogenicity
• inhibitors