BAY 94‐9027, an investigational factor VIII replacement therapy being developed by Bayer for severe hemophilia A, is able to stay longer in patients’ blood than other standard therapies, according to a study analyzing data from three clinical trials.
Because BAY 94‐9027 improves the lifetime of factor VIII, which is the missing or deficient clotting protein in hemophilia A patients, it can potentially reduce the number of infusions needed for effective preventive treatment, while maintaining low bleeding rates.
The study, “BAY 94‐9027, a PEGylated recombinant factor VIII, exhibits a prolonged half‐life and higher area under the curve in patients with severe haemophilia A: Comprehensive pharmacokinetic assessment from clinical studies,“ was published in the journal Haemophilia.
Replacement therapy with medicines that contain factor VIII, including Eloctate, Kogenate, and Kovaltry, have proven beneficial as preventive, or prophylactic, treatments for both children and adults with severe hemophilia A.
Several studies have shown that patients who receive prophylactic treatment have fewer bleeding episodes and healthier joints.
But many of the available factor VIII therapies have low stability, requiring frequent intravenous infusions every other day or three times per week, which makes them inconvenient and discouraging to patients.
Therapies with prolonged action have the potential to maintain therapeutic levels of factor VIII for longer periods of time between infusions, lengthening bleeding protection and reducing the number of infusions needed.
BAY 94-9027 is an investigational recombinant (lab-made) factor VIII (rFVIII) for severe hemophilia A intended to extend the amount of time the clotting factor is able to stay in the blood. It consists of factor VIII lacking one of its regions, called B-domain, and attached to a chemical group called polyethylene glycol (PEG) — a non-toxic and non-immune reactive molecule.
The addition of PEG, or PEGylation, was used reduce the therapy’s ability to trigger an immune response and increase its stability. PEG can increase the amount of time a medication stays in circulation, prolonging its half-life, or the time it takes for a drug’s effectiveness to lower by half in the blood.
BAY 94-9027 “was developed with the goal of providing good protection from bleeding with less frequent infusions,” the researchers wrote in the study.
To address how efficient BAY 94-9027 is in extending the lifetime of clotting factor VIII, researchers collected data from three separate clinical trials that evaluated the effects of BAY 94-9027 in adult, adolescents, and children with hemophilia A.
These trials gathered data regarding BAY 94-9027’s pharmacokinetics, meaning how the therapy is absorbed, distributed, and eliminated by the body.
The study included data from 14 patients in an open-label Phase 1 trial (NCT01184820), where BAY 94-9027 demonstrated a 1.4 times longer half-life than Kogenate, a standard recombinant factor VIII, in adults, ages 18 to 65.
Researchers also looked at 22 patients enrolled in a Phase 2/3 trial called PROTECT-VIII (NCT01580293). This study showed that BAY 94-9027 is well-tolerated and prevented bleeds at dose intervals as few as once every seven days in adults and adolescents, ages 12 to 65.
Additionally, 34 children enrolled in the ongoing Phase 3 PROTECT-VIII Kids (NCT01775618) were analyzed. This study is evaluating the effectiveness and safety of the the therapy in children younger than 12 with hemophilia A.
Early data from this trial shows that BAY 94-9027 is able to control bleeds in all tested treatment regimens — twice weekly, every five days, and every seven days — further supporting the therapy’s safety and long-lasting effectiveness Final results of this trial have not yet been published.
Researchers calculated the pharmacokinetic parameters of BAY 94-9027 separately for each trial, as well as combining results from all three trials.
According to their analysis, compared with a standard formulation of factor VIII, BAY 94-9027 was eliminated more slowly from the body, resulting in an increase of about 40 percent in the half-life and duration of the clotting factor in the plasma of patients.
The therapy’s pharmacokinetic profile did not seem to change significantly between single and multiple administrations.
In addition, they found dose-proportional increases for doses between 25-and 60 IU/kg.
Consistent with other factor VIII products, BAY 94-9027’s pharmacokinetics were dependent on age. Following a single 60-IU/kg dose, clearance from the blood was similar in adolescents and adults but higher in children.
The therapy also took less time to reduce by half in the plasma of children — between 14.5 and 15.6 hours — compared with adolescents (17.8 hours) and adults (16.9 hours).
During prophylactic replacement therapy, the longer a patient spends with low factor VIII levels, which are considered less than 1 percent, the higher the risk of bleeding, particularly in children.
The longer half-life of BAY 94-9027 seen in the clinical trials “suggests that patients can be above threshold levels for longer duration, with higher FVIII levels between infusions and therefore can extend the interval between prophylaxis infusions while maintaining low bleeding rates,” the researchers said.