Antihemophilic factor

Personalized prophylaxis with a recombinant factor VIII product allowed for reduced dosing while still providing protection from bleeds in a small study of patients with severe hemophilia A.

Researchers tested pharmacokinetic (PK)-guided prophylaxis with simoctocog alfa in previously treated patients with severe hemophilia A.

The approach reduced the dose administered and increased the dosing interval compared to standard prophylaxis, without compromising protection from bleeds.

Researchers reported these results in the journal Haemophilia. The research was sponsored by Octapharma AG, the company marketing simoctocog alfa as Nuwiq.

Simoctocog alfa is a fourth-generation recombinant human factor VIII product produced in a human cell line.

In this phase 3b study, researchers tested PK-guided prophylaxis with simoctocog alfa in 66 previously treated adults with severe hemophilia A.

The patients’ mean age at baseline was 33.6. Most (62%) had received on-demand treatment in the 6 months prior to starting the study. Prophylaxis was largely irregular in the 38% of patients who received prophylaxis.

At baseline, the mean annualized bleeding rates (ABRs) were 38.9 in the entire cohort, 45.6 in the on-demand cohort, and 27.8 in the prophylaxis cohort.

Study design

The study had 3 phases. The first was the 72-hour PK phase. Patients received a single dose of simoctocog alfa (60 ± 5 IU kg^–1) and had blood samples taken at various time points. This helped the researchers determine the patients’ personalized prophylaxis regimen.

The second phase of the study was the standard prophylaxis phase, which lasted 1 to 3 months. In this phase, patients received simoctocog alfa at a dose of 30 to 40 IU kg^–1every other day or 3 times a week until they began personalized prophylaxis.

The third phase was the 6-month personalized prophylaxis phase. A patient’s personalized prophylaxis regimen was based on individual PK modeling for each patient according to whether their PK profile most closely fit a 1- or 2-compartment model. In cases of uncertainty, the researchers used a non-compartment model.

A 2-compartment PK model was used for 36 patients, a 1-compartment model was used for 23 patients, and a non-compartment model was used for 7 patients.

Dosing

In total, the patients received 6612 infusions of simoctocog alfa.

During standard prophylaxis, the mean treatment duration was 2.7 months. Patients received a mean of 34.0 infusions and a total dose of 1157.6 IU kg^–1.

During the personalized prophylaxis phase, the mean treatment duration was 6.2 months. Patients received a mean of 58.8 infusions and a total dose of 2574.4 IU kg^–1.

The median dosing interval was 3.5 days during personalized prophylaxis, 3.5 days in the 1- and 2-compartment model groups, and 2.3 days in the non-compartment group. Fifty-seven percent of patients had twice-weekly dosing or less.

In the standard prophylaxis period, patients were dosed every other day or 3 times a week.

The median weekly dose was 100.0 IU kg^–1 during standard prophylaxis and 95.0 IU kg^–1 during personalized prophylaxis. It was 97.5 IU kg^–1 during months 1 to 4 of personalized prophylaxis and 92.8 IU kg^–1 during months 5 and 6 of personalized prophylaxis.

Bleeding and safety

Similar percentages of patients were bleed-free during the roughly 3-month standard prophylaxis period and the roughly 6-month personalized prophylaxis period—76.9% and 73.8%, respectively.

However, the mean ABR was 3.16 for the standard prophylaxis period and 1.45 for the personalized prophylaxis period. The median ABR was 0 for both periods.

In all, there were 95 breakthrough bleeds—46 during standard prophylaxis and 49 during personalized prophylaxis—in 23 of the patients. All of these bleeds were treated with at least 1 dose of simoctocog alfa.

There were no serious adverse events associated with treatment, and none of the patients developed factor VIII inhibitors.

One patient experienced malaise and dizziness after a single infusion during the standard prophylaxis period. These events were considered treatment-related, but both events resolved.

PK-guided prophylaxis reduces dosing, still prevents bleeds