The study, “Real‐world data of immune tolerance induction using recombinant factor VIII Fc fusion protein in patients with severe haemophilia A with inhibitors at high risk for immune tolerance induction failure: A follow‐up retrospective analysis,” was published in the journal Haemophilia. It was sponsored by Sanofi, which markets Eloctate.
Hemophilia A is caused by a lack of functional factor VIII (FVIII), a protein involved in blood clotting. A standard treatment for hemophilia A is replacement therapy — administering FVIII to replace the faulty protein. However, more than a quarter of people with hemophilia A will develop inhibitors or antibodies that bind to the administered FVIII, preventing it from functioning properly.
Immune tolerance induction (ITI) is the only strategy known to be effective for removing inhibitors. Conceptually, it involves giving a person high doses of FVIII to “train” their body not to mount an immunological response to the therapy, a phenomenon called tolerance.
Eloctate is an extended half-life FVIII therapy — a lab-made version of the protein engineered to last longer in the body. Preliminary reports have suggested that Eloctate and other extended half-life therapies may induce tolerance more quickly than standard FVIII therapies.
In the study, a team including researchers at Sanofi reviewed patient data from 13 sites in the U.S. and Canada. They identified 29 people who had undergone ITI with Eloctate; of these, 10 were undergoing ITI for the first time, while the remaining 19 were undergoing rescue ITI (meaning they had failed at least one previous ITI attempt). Median age when ITI was started was 1.4 years for first-timers and 6.5 years for rescue patients.
Varying dosing regimens were used in the different patients.
Of the 10 patients undergoing ITI for the first time, nine had a negative Bethesda titer (a measure of inhibitors) and were deemed to have achieved tolerance after a median of 30 weeks — around seven months.
Eight of these patients transitioned to prophylactic (preventive) treatment with Eloctate; the remaining one, who had low levels of detectable inhibitors, was still on ITI when the data were assessed. The 10th first-time patient, who had a positive Bethesda titer, was also still on ITI.
Of the 19 patients undergoing rescue ITI, 10 had a negative Bethesda titer after a median of 21 weeks, about five months. Four of these patients were deemed to have reached tolerance; three went on prophylactic Eloctate, while the fourth relapsed and switched back to ITI. The remaining rescue patients were either still on ITI or undergoing treatment with other therapies when the data were analyzed.
“Our results match previous observations that achieving successful tolerization in rescue ITI patients is generally difficult and much less likely to be successful, making the first attempt at ITI most important,” the researchers wrote.
No adverse events related to Eloctate treatment were reported among all the patients.
“This retrospective chart review in a real-world setting shows that first-time ITI patients achieved rapid tolerization with a high success rate [using Eloctate],” the researchers wrote. “The results demonstrate a shorter median time to tolerization with rFVIIIFc [Eloctate] ITI than reported with other FVIII regimens.”
Limitations of the study include the small sample size. Currently, Eloctate ITI is being evaluated in the verITI-8 clinical trial (NCT03093480). Positive interim results from this study have been reported.