Interim results of the ASPIRE trial suggest extended treatment or prophylaxis with a recombinant factor VIII Fc fusion protein (rFVIIIFc/efmoroctocog alfa, Eloctate/Elocta) can be safe and effective for hemophilia A patients of all ages.
Patients could enroll in the phase 3 ASPIRE trial after completing the A-LONG and Kids A-LONG studies.
At the time of the interim analysis, most patients had at least 100 days of cumulative exposure to rFVIIIFc.
None of the patients developed inhibitors, and the investigators said adverse events (AEs) were generally consistent with those expected in the general hemophilia A population.
Furthermore, the median annualized bleeding rates (ABRs) were low among patients receiving prophylaxis, and most patients had no change in prophylactic infusion frequency or total weekly prophylactic dose.
These results appear in Haemophilia. The trial is sponsored by Biogen, the company developing rFVIIIFc.
Trial design
ASPIRE has enrolled 211 males with hemophilia A, including 150 (98%) of those who completed A-LONG and 61 (91%) of those who completed Kids A-LONG.
ASPIRE has an on-demand treatment group and 3 prophylactic treatment groups: individualized, weekly, and modified prophylaxis. In the on-demand group, dosing is based on the type and severity of bleeding episodes.
Subjects in the individualized prophylaxis group receive rFVIIIFc at 25-65 IU kg−1 every 3 to 5 days or twice-weekly rFVIIIFc at 20–65 IU kg−1 on day 1 and 40–65 IU kg−1 on day 4. In subjects younger than 12, the investigators can make dose adjustments.
The weekly prophylaxis group receives rFVIIIFc at 65 IU kg−1 every 7 days. Patients who cannot receive optimal treatment in either the individualized or weekly prophylaxis groups can be placed in the modified prophylaxis group.
Patients can change their treatment group at any time during the study. However, subjects younger than 12 can only participate in the individualized and modified prophylaxis groups.
“The design of the ASPIRE study provides physicians a high degree of dosing flexibility, with the goal of reflecting their real-world treatment practices,” said Guy Young, MD, of Children’s Hospital of Los Angeles in California.
Treatment
As of the interim analysis, the median time in the ASPIRE study was 80.9 weeks for adults and adolescents completing the A-LONG study and 23.9 weeks for children completing the Kids A-LONG study. The median cumulative duration of treatment was 117.7 weeks for adults and adolescents and 51.5 weeks for children.
Nearly all Kids A-LONG subjects (96.7%) continued on individualized prophylaxis. Two subjects switched to the modified prophylaxis group upon enrollment in ASPIRE, but none of the subjects changed their treatment group during ASPIRE.
Of the A-LONG subjects, 16.7% changed treatment groups at enrollment in ASPIRE, and 11.3% made a change to their treatment group during ASPIRE. None of the subjects changed treatment groups more than once.
Most patients who were previously on a prophylactic regimen in A-LONG had either no change to their infusion interval (71.9%) or had a longer infusion interval (21.9%) during ASPIRE. Most patients on Kids A-LONG (95.1%) had no change to their prophylactic infusion interval on ASPIRE.
Safety
Overall, 65.4% of subjects had at least 1 AE, and 10.9% had at least 1 serious AE. All of the serious AEs were considered unrelated to rFVIIIFc, and all had resolved by the time of the interim data cut. There were no serious allergic reactions, serious vascular thrombotic events, or deaths.
The most common AEs (incidence of 5% or greater) were nasopharyngitis (12.8%), upper respiratory infection (7.6%), and arthralgia (5.2%). Three adults (1.4%) experienced 4 mild AEs that were thought to be related to rFVIIIFc—chromaturia, elevated blood creatinine, and headache/hot flashes.
Efficacy
For adults and adolescents, the overall ABR was 0.66 in the individualized prophylaxis arm, 2.03 in the weekly prophylaxis arm, 1.97 in the modified prophylaxis arm, and 18.36 in the on-demand treatment arm.
For children in the individualized prophylaxis arm, the overall ABR was 0.00 in children younger than 6 and 1.56 in those ages 6 to 11. For children in the modified prophylaxis arm, the overall ABR was 6.55 in those younger than 6 and 0.00 for children 6 to 11.
A total of 566 bleeding episodes occurred in adults and adolescents who were treated prophylactically. Patients in the on-demand treatment arm experienced 262 bleeding episodes.
Overall, 90.8% of these bleeding episodes were controlled with a single infusion of rFVIIIFc, and 96.9% of the episodes were controlled with 1 or 2 infusions.
Children had a total of 51 bleeding episodes—23 among children younger than 6 and 28 among children 6 to 11.
Most of these episodes were controlled with a single infusion of rFVIIIFc—82.6% among children younger than 6 and 82.1% among children 6 to 11. And 95.7% and 89.3%, respectively, were controlled with 1 to 2 infusions.
“The results suggest prophylaxis with Eloctate shows efficacy and safety for the long-term treatment of hemophilia A,” Dr Young concluded.
