Novo Nordisk reported results from two phase 2 studies, Explorer4 and Explorer5, which evaluated concizumab for the prevention of bleeding episodes in patients with hemophilia A (explorer5 study) and hemophilia A/B with inhibitors (explorer4 study).
The phase II studies showed annual bleeding rates comparable to factor prophylaxis despite many patients being undertreated due to conservative dosing rules. Treatment with concizumab was well tolerated, with no adverse event-related withdrawals and no thromboembolic events.
A Phase III study evaluating concizumab is expected to commence later this year.
Novo Nordisk also reported on two new interim analyses of the paradigm5 and paradigm6 studies in pediatrics. Nonacog beta pegol (N9-GP, Refixia) demonstrated low annual bleeding rates and was well tolerated in children with hemophilia B, supporting the long-term safety and efficacy already established in previous studies. In the five-year interim analysis of paradigm5, bleeding rates in previously treated children (≤12 years) with hemophilia B were low and had declined after five years of treatment versus one year of treatment.
The efficacy and safety profile of Refixia was further supported by the first interim results of ≥20 patients completing 50 exposure days (EDs) in paradigm6. Previously untreated children (<6 years) on weekly prophylaxis reported low bleeding rates and good bleed resolution with median annualized bleeding rates (ABRs) of 0.0 for overall, spontaneous and traumatic bleeds.
About Hemophilia A and B
Hemophilia is an inherited bleeding disorder in which the blood does not clot properly. This can lead to spontaneous bleeding as well as bleeding following injuries or surgery. Blood contains many proteins called clotting factors that can help to stop bleeding. People with hemophilia have low levels of either factor VIII (hemophilia A) or factor IX (hemophilia B). The severity of hemophilia that a person has is determined by the amount of factor in the blood. The lower the amount of the factor, the more likely it is that bleeding will occur which can lead to serious health problems.
Concizumab is a monoclonal antibody against Tissue Factor Pathway Inhibitor (TFPI) intended for bleeding prevention after subcutaneous administration.
Refixia is a modified form of factor IX that is used as replacement therapy to replenish the deficient protein. Refixia contains a polyethylene glycol (PEG) molecule attached to the portion of factor IX protein that is broken off when the clotting factor is activated. The addition of PEG helps extend the half-life of factor IX. This process is called PEGylation and prevents the premature breakdown of factor IX by using naturally occurring antibodies against it.
Refixia has been approved by both the U.S. FDA and the EMA.