Two major therapeutic breakthroughs in hemophilia A were presented at the American Congress of Hematology, ASH 2017. They will profoundly change the lives of patients in the short and long term.
Two new drugs significantly reduce bleeding due to Factor VIII deficiency and will improve the lives of type A hemophiliacs. They were presented at the American Congress of Hematology, ASH 2017.
One concerns a bispecific antibody, tested subcutaneously on 60 children with hemophilia A, which mimics the role of Factor VIII, the missing clotting factor, and it drastically reduces bleeding. The other concerns gene therapy in a preliminary study in 13 adults, but which gives hope for a cure in the long term for the patients who will benefit from it.
Emicizumab replaces factor VIII
In a controlled phase III trial in children, emicizumab improves 95% of children with hemophilia who no longer have any hemorrhagic episode requiring factor VIII replacement therapy. The researchers treated 60 children aged 1 to 12 who had a Factor VIII inhibitor, which prevented them from being treated effectively with the Factor VIII replacement infusions.
This shows that emicizumab, a bispecific anti-factor Xa and X monoclonal antibody that acts as a factor VIII cofactor, is effective in preventing hemorrhages associated with hemophilia A, the most common form and the most complex to treat hemophilia. These benefits are not accompanied by serious adverse events associated with emicizumab.
Correct tolerance
Emicizumab works like Factor VIII, therefore allowing the blood to clot, but it has a different structure, which makes it unrecognizable by anti-Factor VIII antibodies.
In some patients, repeated infusions of Factor VIII cause the body and its immune system to develop antibodies which bind to the replacement Factor VIII provided by the infusion and make it ineffective.
Previous studies with emicizumab, conducted in adults and adolescents, had raised concerns about the safety of the product due to bleeding in a few patients during administration of the drug. This was not observed in this trial in children, possibly because the children in this trial used Factor VIII less often since they had Factor VIII infusion less often than adults.
Gene therapy in adults
In a second study on hemophilia A, but in adults this time, a single infusion of an experimental genetic treatment results in greatly improved levels of Factor VIII, the blood clotting protein, which is no longer made in hemophilia A due to the alteration of the gene. Eleven out of 13 adults achieved normal or near normal levels of Factor VIII up to 19 months of follow-up.
Gene therapy uses a viral vector to transfer a functional copy of the gene responsible for the production of Factor VIII into the patient’s body, which is mutated in people with hemophilia A and therefore defective.
This is the first successful gene therapy trial in hemophilia A. Although several gene therapies have been shown to be effective in hemophilia B, a rarer form, gene therapy for hemophilia A is considered more difficult. because it is associated with a much larger and more complex gene. Unlike the multiple intravenous infusions per week of the usual treatment, this gene therapy appears to have lasting effects with a single infusion.
Serious and recurrent bleeding
Hemophilia affects nearly 5,000 people in France, half of them in its major form. There are 2 forms depending on the diseased gene and the missing coagulation protein. Because of this missing protein, the blood of a person with hemophilia does not clot normally. People with hemophilia A produce extremely low levels of Factor VIII, the protein necessary for blood to clot.
Without treatment, patients can suffer from severe bleeding, several times a month, especially in the joints, causing severe pain, with a risk of secondary joint disease: hemophilic arthropathy. The treatment available to prevent bleeding is frequent intravenous infusions of Factor VIII.
Before these treatments, we did not have any methods other than Factor VIII transfusions to prevent joint hemorrhages in hemophiliacs A. The risk has been of transmitting infections in the past and it is still to develop anti-Factor antibodies. VIII which currently reduce its effectiveness.
Emicizumab has been shown to be very effective in preventing life changing bleeding events in children. Gene therapy for hemophilia A represents a scientific breakthrough with the hope of a definitive cure for this disease.
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