Clinical Trial Results of 3 Hemophilia Treatments, Two Now in Use, Published

Key findings from clinical trials of three recombinant coagulation factors as new hemophilia treatments, presented at last year’s Congress of the International Society on Thrombosis and Haemostasis (ISTH 2015), have been published in a supplemental issue of the journal Thrombosis Research.

The results were presented in a session during the meeting, hosted by CSL Behring, which also developed the three factors, two of which are now in use. An editorial, running under the same title as the meeting session, “Pioneering therapeutic proteins in hemophilia care through innovative technologies,” said the findings marked a major milestone in hemophilia care, improving treatment and reducing its burden.

The studies in the supplement describe the clinical development of two treatments aiming to allow longer intervals between dosing, and a factor with a better stability than current compounds. Details of these studies are below:

“The story of a unique molecule in hemophilia A: recombinant single-chain factor VIII,” by Ingrid Pabinger-Fasching, a professor at the Medical University of Vienna, Austria, described the clinical development of recombinant single-chain factor VIII (rVIII-SingleChain) for the treatment of hemophilia A. The study summary showed that the new molecule has better characteristics than earlier factor VIII products, having a better stability and a  stronger binding to von Willebrand factor. The molecule went through Phase 1 to 3 clinical studies in the AFFINITY clinical trial program, with encouraging results. Findings in the trials showed the molecule to have a good effect when used on demand, for prevention, and during surgery. It was also well-tolerated. The AFFINITY program is now continuing to study the factor in an extension study and in a study involving children.

The factor, marketed as Afstyla, was approved by the U.S. Food and Drug Administration (FDA) for adults and children with hemophilia A in May, based on AFFINITY trial results. It is indicated for routine prophylaxis to reduce the frequency of bleeding episodes, for on-demand treatment and control of bleeding episodes, and for perioperative management of bleeding.

The second article, “Transforming the treatment for hemophilia B patients: update on the clinical development of recombinant fusion protein linking recombinant coagulation factor IX with recombinant albumin (rIX-FP),” by Dr. Elena Santagostino from University of Milan in Italy, described the progress of the development of rIX-FP (recombinant fusion protein linking recombinant coagulation factor IX with recombinant albumin). This fusion, intended to allow longer dosing intervals, has been tested in two Phase 3 studies in the PROLONG-9FP trial program. These trials explored the drug in adults, adolescents, and children with severe hemophilia B, showing that compared to earlier factor IX compounds that were administered every three or four days, the rIX-FP could be given every seven to 14 days when used for prevention.

Marketed by CSL Behring as Idelvion, rIX-FP was approved by the FDA to treat children and adults with hemophilia B in March, with identical indications to Afstyla.

The final study, “Entering new areas in known fields: recombinant fusion protein linking recombinant factor VIIa with recombinant albumin (rVIIa-FP) – advancing the journey,” by Claude Négrier, a professor at the Louis Pradel University Hospital in France, focused on another fusion protein, targeting factor VIIa, also attempting to increase the time between doses. A Phase 1 trial, exploring the drug in healthy volunteers in the PROLONG-7FP program, showed promising results, and the protein is now being tested in patients with both hemophilia A and B, as well as in patients with congenital factor VII deficiency.