In hemophilia A, a mutation in the gene coding for clotting factor VIII (FVIII) makes patients prone to bleeds in muscles and joints. To prevent bleeding and minimize joint damage, intravenous (into-the-vein) injections of FVIII are recommended as a standard treatment.
Kovaltry, marketed by Bayer, is an engineered FVIII that has been approved for the treatment of children and adults with hemophilia A in Europe, the U.S., and Canada. However, according to the researchers, real-world evidence is lacking for the therapy’s value in children.
While many FVII replacement treatments are extended half-life (EHL) products — meaning they’re designed to last longer in the body — Kovaltry is a standard half-life therapy. Yet, clinical data have shown that Kovaltry is able to remain longer in the body of people with hemophilia A than traditional FVIII medicines.
Now, an international team of researchers sought to describe Kovaltry’s effectiveness in children with hemophilia A in the real world. To do so, they used data obtained between December 2017 and April 2018 from the pediatric CHESS study, fully known as Cost of Haemophilia in Europe: a Socioeconomic Survey.
The study included boys, younger than 18, with moderate or severe hemophilia A, from five European countries — France, Germany, Italy, Spain, and the U.K. The boys had received either Kovaltry or EHL products.
In the analysis, which was funded by Bayer Consumer Care, the patients were divided into three age groups: younger than 5, 6–11 years, and 12 and older. Efficacy was measured based on the annualized bleeding rate (ABR) — the rate of bleedings per year — and the annual FVIII utilization rate.
Most of the 29 boys receiving Kovaltry had severe hemophilia (93.1%). At the start, 22 patients (75.9%) were on continuous preventive (prophylaxis) treatment, and target joints, those with recurrent bleeding and inflammation, were rare (10.3%).
The mean ABR in patients on Kovaltry was 2.66, with rates decreasing with age. Specifically, the rates were 4.0 in the younger group and 1.89 in boys 12 and older. About 20% of these patients were free of bleeds.
In turn, in patients receiving preventive Kovaltry treatment, the mean ABR was 2.18. These children received on average 2.45 infusions per week (median 3).
No adverse events were reported, nor was any development of inhibitors (neutralizing antibodies). Most patients adhered to the prescribed treatment (86.2%) and were satisfied or very satisfied with it.
The team conducted an exploratory analysis involving 82 patients — 22 on Kovaltry and 60 on EHL therapies. The two groups differed considerably, in that boys receiving Kovaltry were younger, had severe disease more often (90.9 vs. 80%), and started preventive treatment earlier. Patients in the EHL group were more likely to have had recurrent inhibitors (6.7% vs. 0%), target joints (18.3% vs. 9.1%), and damaged joints (21.7 vs. 4.5%).
After accounting for factors such as age, disease severity, and FVIII usage, the researchers did not find significant differences in ABR between the two types of treatment. ABR remained lower in patients treated with Kovaltry across all age groups, and a higher proportion of patients had zero bleeds when compared with the EHL group (27.3 vs. 10%). Adherence to treatment was high among all the boys (above 80%) and similar between the groups.
Median FVIII utilization was lower in the Kovaltry group than in the EHL group (74.84 vs. 88.83 international units/kg), but this difference was not statistically significant. Additionally, no difference was seen in mean weekly infusion frequency.
“The noted non-significant differences in ABR and utilization must be interpreted cautiously in light of the low sample size, due to the disease rarity, limited available EHLs at the time of the study, restriction of use to only patients aged above 12 years for Adynovi [Adynovate], and potential for residual confounding factors. Full clinical details of joint involvement, such as imaging, were also not available in the study dataset,” the researchers wrote.
Yet, “this analysis demonstrates the effectiveness and safety of Kovaltry in a pan-European pediatric population with severe hemophilia A,” they concluded.