The bispecific monoclonal antibody emicizumab was an effective prophylactic treatment for infants with severe hemophilia A without factor VIII (FVIII) inhibitors, according to data from the phase III HAVEN-7 study presented at the 65th ASH Annual Meeting and Exposition.1
“I firmly believe that the HAVEN-7 results have established a new standard of care for management of infants from shortly after birth, and I expect that advisory groups will amend their recommendations accordingly,” study presenter Steven Pipe, MD, of the University of Michigan at Ann Arbor, told ASH Clinical News.
Many infants with hemophilia A cannot receive FVIII prophylaxis until age 1 year or beyond because of the challenges of administering the treatment. The U.S. Food and Drug Administration approved emicizumab for adult and pediatric patients with hemophilia A with FVIII inhibitors in 2017, with the approval later expanded to include all ages. At that time, the Medical and Scientific Advisory Council to the National Bleeding Disorders Foundation (formerly National Hemophilia Foundation) recommended that “infants should be considered for prophylaxis with emicizumab at any time after birth given the increased risk of intracranial hemorrhage prior to initiation of FVIII prophylaxis.”2
“The challenge for clinicians was that clinical trial and real-world experiences with very young infants — particularly those less than a few months of age — were lacking,” Dr. Pipe said.
The HAVEN-7 study was designed to evaluate the efficacy and safety of emicizumab in infants younger than 1 year without FVIII inhibitors.
Trial participants received 3 mg/kg of subcutaneous emicizumab weekly for four weeks, then every two weeks for 52 weeks. During the seven-year follow-up, participants could continue this dosing regimen or switch to either 1.5 mg/kg weekly or 6 mg/kg every four weeks.
The trial included 55 participants who all received emicizumab for at least 52 weeks; all were male. Median age at enrollment was 4 months, and median age at the clinical cutoff date was 29 months.
More than half (54.5%) of participants had zero treated bleeds. The annualized bleed rates for all bleeds and treated joint bleeds were 2.0 and 0.0, respectively. All treated bleeds were categorized as traumatic by families and treaters.
No participants had more than three treated bleeds. The majority of participants (67.3%) had between zero to three bleeds, and 16.4% had no bleeds.
No new safety signals were observed. All participants experienced at least one adverse event (AE), including 16.4% who had at least one drug-related AE; however, no AEs led to treatment changes or trial withdrawal. No intracranial hemorrhage occurred. About one-third (29.1%) of patients had serious AEs, but none were deemed related to the study drug.
Dr. Pipe said emicizumab allows for a transformational experience for families with a new infant with hemophilia A. In the past, clinicians had to explain to families that initiation of FVIII prophylaxis would be too challenging given the difficult venous access and the requirement in most cases for a central venous access device with the potential for significant associated complications, he explained.
“This left them throughout the whole first year of life with uncertainty about what would happen with minor injuries, anxiety about activity levels as the infants became more mobile, and intermittent trips to the emergency room or the clinic for infusions, upending their lives,” Dr. Pipe said. “Families that had prior experience with their older children with hemophilia have commented how it was a night-and-day difference having their infant on prophylaxis with emicizumab.”
Any conflicts of interest declared by the authors can be found in the original abstract.
Reference
Pipe S, Collins P, Dhalluin C, et al. Emicizumab prophylaxis in infants with severe hemophilia A without Factor VIII inhibitors: results from the primary analysis of the HAVEN 7 Study. Abstract 505. Presented at the 65th American Society of Hematology Annual Meeting and Exposition; December 10, 2023; San Diego, California.
