Characterizing Emicizumab with Immune Tolerance Induction Therapy in Hemophilia A

Emicizumab treatment combined with immune tolerance induction (ITI) therapy to eliminate factor VIII (FVIII) inhibitory antibodies did not exhibit new safety signals nor an increased rate of thrombotic events in patients with hemophilia A, according to a 48-week interim analysis of the phase IV AKATSUKI trial.

The preliminary data was presented by Tadashi Matsushita, MD, PhD, from the Nagoya University Hospital in Aichi, Japan, at the 65th American Society of Hematology Annual Meeting & Exhibition in San Diego, California.

A total of 12 patients with a median age of 2.5 years (range, 1-54) were including in the interim analysis. By the data cutoff of December 22, 2022, the median evaluation period was 437.5 days (range, 224-749). The primary end point was rate of adverse events (AEs), particularly thrombotic events, and laboratory values during and immediately following ITI therapy. Key secondary end points included the number of treated bleeding events and the number of patients who succeeded ITI therapy.

Dr. Matsushita stated 30 AEs occurred, none of which were deemed related to emicizumab or FVIII concentrate, and no patients experienced a thrombotic event. Serious AEs occurred in two patients, one case of pneumonia caused by transmission of viral infection and one case of accidental wound hemorrhage. Three of the 12 patients had a total of 10 bleeding events, all of which were categorized as traumatic and treated with recombinant activated FVII.

At data cutoff, one patient had achieved partial ITI success with a negative FVIII inhibitor titer at week five and normalized FVIII recovery at week 17. The patient then initiated emicizumab plus FVIII concentrate maintenance therapy, during which no bleeding events or AEs were observed.

“This study continues to evaluate the safety of emicizumab in conjunction with, and following, ITI therapy in [patients with hemophilia A] with FVIII inhibitors,” Dr. Matsushita and colleagues stated.

Reference

Matsushita T, Suzuki N, Nagae C, et al. AKATSUKI 48-week interim analysis: emicizumab and immune tolerance induction in people with hemophilia A and factor VIII inhibitors. Abstract #2625. Presented at the 65th ASH Annual Meeting & Exposition; December 9-12, 2023; San Diego, California.