Hemlibra Given with Immune Tolerance Induction Safely Treats Children with Severe Hemophilia A, Study Finds

Combining immune tolerance induction, used to prevent the development of anti-factor VIII inhibitors, with Hemlibra (emicizumab) is a feasible and safe way of treating children with severe hemophilia A, a study shows.

Published in the journal Haemophilia, the report covers clinical outcomes in the first seven patients to be given this combo approach, named “The Atlanta Protocol.”

The study is titled “Immune tolerance induction in paediatric patients with haemophilia A and inhibitors receiving emicizumab prophylaxis.”

A deficiency in clotting factor VIII (FVIII) in hemophilia A patients affects their ability to stop a bleed, and standard of care is based on administering recombinant (synthetic) versions of this missing blood clotting factor.

Although available FVIII replacement therapies work well, about 30% of patients will develop antibodies — inhibitors — against factor VIII treatments that neutralize their effectiveness. In fact, the production of FVIII inhibitors is the most common complication in hemophilia A care today, the study notes.

Hemlibra, by Roche, is a non-factor replacement therapy to treat hemophilia A patients with or without inhibitors. It works as a bypassing agent to mimic the activity of FVIII, and is widely used in both the United States and Europe as a routine and preventive hemophilia A treatment.

While effective, Hemlibra does not help to rid a person of FVIII inhibitors. Immune tolerance induction (ITI) — in which FVIII is given regularly over a period of time until the body is trained to recognize the product without reacting against it — is the only effective strategy to removing inhibitors and restoring a normal response to FVIII replacement therapy.

Researchers at Emory University School of Medicine, in collaboration with the Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta, reviewed a case series of children with severe hemophilia A and inhibitors treated under The Atlanta Protocol. This protocol is a modified treatment strategy, in that it combines ITI to manage inhibitor levels at the same time as Hemlibra is being given to prevent or stop bleeding.

The study group included seven children between 21 months and 12 years old. They were started on a combination of ITI with FVIII infusions three times a week plus Hemlibra, and followed for a median time of 35 weeks (about nine months).

Treatment for three of the seven led to either a complete clearing of inhibitors or a drop to unmeasurable levels, results show. Three patients (43%) also had no bleeding events, and a total of nine bleeding events were reported among the other four during follow-up. No adverse effects, such as blood clots, were reported.

Six children underwent surgery during this study, with no major complications or excess bleedings during or after surgery. Length of hospital stays for these patients also decreased, changing from an average of three-to-seven days to one-to-two days, the researchers noted.

They believes their work “is the first” to demonstrate that “immune tolerance induction while on emicizumab [Hemlibra] prophylaxis is a feasible approach in pediatric hemophilia A patients with inhibitors.”

“This study is incredibly valuable as it provides the first evidence that ITI is safe and feasible when given in combination with emicizumab,” Robert Sidonio, MD, an associate director of the Hemostasis and Thrombosis Program at Children’s Healthcare of Atlanta, an assistant professor of pediatrics at Emory, and a study author, said in a press release. “Prospective studies will be necessary to compare treatment outcomes to standard ITI regimens, but we are encouraged by the early success of ‘The Atlanta Protocol.’”

Two observational clinical trials are preparing to further explore the safety and effectiveness of The Atlanta Protocol in hemophilia A children and adults: the MOTIVATE study (NCT04023019) (at two sites; Children Healthcare of Atlanta and a center in Germany), and the Emicizumab PUP and Nuwiq ITI study (NCT04030052), taking place at Emory. Both trials are not yet enrolling patients but expect to shortly; information is available by clicking on their respective NCT numbers.

“As the global hemophilia community began discussing how to adapt ITI in the era of emicizumab [Hemlibra] prophylaxis, our new ITI approach, ‘The Atlanta Protocol,’ has been a focus,” said Shannon Meeks, MD, a pediatric hematologist/oncologist at Children’s Healthcare, associate professor at Emory, and a study co-author. “We believe that this new, formalized way of tackling the problem of inhibitors can potentially improve treatment outcomes and give more hope to families living with hemophilia.”