Add-on therapy may speed immune tolerance in children with hemophilia A
Small study links add-on therapy to faster tolerance, fewer bleeds
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- Some patients with severe hemophilia A develop inhibitors that can reduce the effectiveness of factor replacement therapy.
- Immune tolerance induction aims to eliminate inhibitors but can take months, with bleeding remaining a challenge.
- Adding Hemlibra was linked to faster immune tolerance, significantly fewer treated bleeds, and no increase in direct treatment costs.
In children with severe hemophilia A who are undergoing treatment to remove inhibitors, adding Hemlibra (emicizumab-KXWH) was associated with faster immune tolerance and fewer treated bleeds.
Adding Hemlibra also did not increase direct treatment costs during immune tolerance induction, study data showed. The work was partially funded by Roche, a co-developer of Hemlibra.
“In this single-center cohort study with historical controls, [using Hemlibra during treatment to remove inhibitors] was associated with accelerated tolerance, elimination of bleeding during treatment, and no increase in overall direct costs, with a consistent benefit observed across all assessed endpoints,” researchers wrote in the study, “Emicizumab enables rapid tolerance, reducing bleeding during low-dose ITI in pediatric hemophilia A,” which was published in Blood VTH.
How inhibitors complicate hemophilia A treatment
Hemophilia A is caused by a deficiency of the clotting protein factor VIII (FVIII). Standard treatment involves factor replacement therapy, in which a functional version of the FVIII protein is administered to normalize clotting. Although this type of treatment is generally effective, some patients, particularly those with severe hemophilia A, develop antibodies that target the replacement FVIII protein. These antibodies are known as inhibitors because they can stop factor replacement treatments from working effectively.
Immune tolerance induction, or ITI, is a treatment that aims to reeducate the immune system to stop producing inhibitors. Successful ITI can eliminate inhibitors, but treatment often takes months, and bleeding can occur during that time.
Hemlibra, which is approved in the U.S. to treat hemophilia A in patients with or without inhibitors, is an antibody-based therapy that mimics key clotting functions of FVIII without containing FVIII itself. Because it works independently of FVIII, Hemlibra can provide protection from bleeding while ITI is being used to eliminate FVIII inhibitors. However, comparative data on using the two treatments together have been limited.
In this study, researchers in Brazil reported outcomes from nine children with severe hemophilia A and high-responding inhibitors who underwent low-dose ITI while also receiving Hemlibra. Seven of them, or 78%, achieved complete ITI success. Among those who achieved complete success, the median time to success was nine months. Seven of the nine children had no treated bleeds during ITI.
To put these data in context, the researchers compared the findings with those from 14 children with severe hemophilia A who had undergone low-dose ITI at the same center without using Hemlibra. Among these patients, 36% achieved complete ITI success. Among those who achieved complete success, the median time to success was 19 months, and all 14 experienced at least one treated bleed during ITI.
Hemlibra linked to faster tolerance and fewer bleeds
Mathematical analyses were conducted to look for statistically significant differences — that is, differences unlikely to have occurred by chance if there were no true difference between the groups. Results showed that patients on Hemlibra had a significantly shorter time to ITI success and significantly fewer treated bleeds. However, the proportion of patients who achieved complete ITI success did not differ significantly between the groups, meaning the observed difference in success rates could have been due to chance. No serious adverse events or thrombotic complications occurred in the Hemlibra group.
Hemlibra itself added substantial costs, with a median cost of $66,416 per patient during ITI. However, patients given Hemlibra had much less need for bypassing agents to control bleeds and reached complete ITI success sooner. Median direct treatment costs during ITI were numerically lower with add-on Hemlibra — $84,407 versus $169,581 in the historical group — but the difference was not statistically significant. The researchers noted that the cost analysis was exploratory rather than a formal economic evaluation.
“The addition of [Hemlibra] to low-dose ITI was associated with faster achievement of complete tolerance and complete suppression of bleeding, without increasing direct treatment costs,” the researchers concluded. They added that this study “provides the first quantitative evidence that [Hemlibra]-supported low-dose ITI is associated with accelerated tolerance induction in a pediatric cohort.”
The researchers stressed that the analyses were limited by the small number of patients, making it harder to detect statistically meaningful differences. The study also used a historical control group, which limits causal conclusions. As such, the scientists called for further study into how Hemlibra may be used to optimize ITI. Some study authors also reported financial relationships with Roche.
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