Extended Half-Life FVIII Reduces Bleeds and Injections in Hemophilia A

Those with hemophilia A (HA) who switched from standard half-life factor VIII (FVIII)—a clotting protein these folks lack—to rFVIIIFc, an extended half-life recombinant version that remains in the bloodstream longer, experienced fewer bleeds, required less frequent injections and used less factor overall, according to a study published in Hematology.

The study findings highlight the therapy’s effectiveness in reducing both disease and treatment burden for those with HA.

HA is a genetic bleeding disorder caused by a deficiency of FVIII, a protein essential for normal blood clotting. Folks with severe HA typically require prophylactic treatment with clotting factor concentrates (CFCs) to prevent bleeding and preserve joint health, as repeated bleeding into joints and muscles can cause excruciating pain.

Switching to rFVIIIFc significantly reduces bleeding rates and injection frequency for hemophilia A patients, enhancing treatment efficacy and quality of life. © Ulyana - stock.adobe.com

Standard half-life (SHL) FVIII products are effective at preventing bleeds but require frequent infusions, creating a significant treatment burden that can affect adherence and overall quality of life.

Extended half-life (EHL) FVIII products, including efmoroctocog alfa (rFVIIIFc), were developed to address these limitations. By remaining in the bloodstream longer, rFVIIIFc allows less frequent dosing while maintaining higher FVIII levels, improving bleed protection without increasing the risk of inhibitor development.

Approved for those with HA at all ages, rFVIIIFc has demonstrated sustained efficacy and safety in both clinical trials and real-world settings.

For example, the PREVENT study, conducted across 25 German hemophilia treatment centers, showed that individuals who switched to rFVIIIFc experienced a significant reduction in annualized bleeding rates (ABR), decreased injection frequency and lower factor consumption, similar to findings from the A-SURE study.

In the A-SURE study, researchers evaluated the effectiveness of switching from SHL FVIII to rFVIIIFc, measuring changes in bleeding rates, injection frequency and factor consumption in routine clinical practice.

This 24-month, non-interventional, phase 4 trial was conducted at multiple centers across Europe, comparing rFVIIIFc with SHL FVIII prophylaxis. Researchers also reviewed each participant’s medical data from the 12 months before enrollment.

The study included patients who had received SHL FVIII prophylaxis for at least three months followed by rFVIIIFc for at least three months. Patients were excluded if they had used any other EHL FVIII product or had active FVIII inhibitors. Primary outcomes included ABR, annualized joint bleeding rate (AjBR), weekly injection frequency and weekly factor consumption (IU/kg).

Outcomes were compared for each patient before and after switching to rFVIIIFc, with analyses by age group and timing of the switch. Bleeding events were also tracked in six-month intervals, and safety outcomes were recorded.

Out of 131 patients aged 1 to 76, most began rFVIIIFc prophylaxis before enrollment (n=82), while others switched at enrollment (n=27) or after (n=22). Main reasons for switching were improved bleed prevention (47%), fewer injections (45%) and other factors (8%).

Results revealed that after switching to rFVIIIFc, the mean ABR decreased from 3.7 to 1.8—a reduction of 1.9 bleeds per year. The AjBR fell from 2.4 to 1.1, with the greatest improvements in older patients. Weekly injections decreased from 3.1 to 2.3 on average, while weekly factor consumption dropped from 89.7 to 84.1 IU/kg. Factor use declined in nearly all age groups, except children under 12, where it remained stable or slightly increased.

In addition, out of the 27 patients who switched at enrollment, ABR decreased from 3.4 to 2.6, weekly injections from 2.9 to 2.2 and factor use from 78.3 to 71.3 IU/kg. In a subgroup of 95 patients with six months of treatment before and after switching, more than half reported zero bleeds both before and after the switch, with rates around 56% to 59% over the first year.

These study findings highlight a number of strengths, including consistent results across age groups, similarities with the main A-SURE study and evidence that sustained FVIII levels may help protect joints. The study also suggests potential cost benefits from using less factor, although children under eight had a small increase, likely due to a small sample size.

The study also has its limitations. It looked back at existing data, used different methods to collect information and focused on patients who were already chosen as good candidates for switching treatments. There were fewer patients over 65, but the data still provide useful insights.

Authors note that the findings are still relevant today, since both SHL FVIII and rFVIIIFc are commonly used.

Based on the results, authors also indicate that rFVIIIFc seems to be a safe and effective option for those with HA of all ages. They suggest additional research be conducted to support the benefits of extended half-life FVIII products such as rFVIIIFc for managing HA.