Switch to Kovaltry Seen to Better Protect Boys With Severe Hem A

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by Margarida Maia PhD |

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Boys with severe hemophilia A who switched to Kovaltry (octocog alfa), which replaces a missing clotting protein called factor VIII (FVIII), retained the therapy for longer in the body and had fewer bleeds, a study in China reported.

Findings come from a head-to-head comparison of Kovaltry and three other FVIII replacement therapies commonly used in China.

Researchers also observed that boys with blood types other than group O and with higher blood levels of von Willebrand factor, another clotting protein, benefited the most from switching to Kovaltry.

The study, “Enhanced pharmacokinetics and reduced bleeds in boys with hemophilia A after switching to Kovaltry from other standard half-life factor VIII concentrates,” was published in Research and Practice in Thrombosis and Haemostasis.

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Hemophilia A is caused by the lack of FVIII, a protein that helps the blood clot to stop bleeding. Treatment includes replacement therapies, which involve supplying patients with a version of FVIII that works in the same way as the one they are lacking.

Kovaltry, by Bayer, is one such replacement therapy. It is given as an intravenous (into-the-vein) at-home infusion, with frequency dependent on whether Kovaltry is being used on-demand to treat bleeds, or as a prophylactic therapy to prevent them.

Dosing also depends on the severity of a patient’s symptoms, as well as on the medication’s own pharmacokinetics, or how it moves through and exits the body, which can vary from person to person.

“Patients with similar dosing regimens could have different FVIII levels during their routine prophylaxis,” the researchers wrote.

Compared with other standard half-life FVIII replacement therapies, Kovaltry is reported to have a better pharmacokinetic profile, with a lower clearance and a longer half-life. A medication’s half-life is the time it takes for its levels to drop by half; the longer the half-life, the longer it takes for a medication to be fully eliminated from the body.

Few real-world studies comparing these therapies head-to-head had been done to date, the researchers noted. To make such a comparison, they looked at data covering boys who had switched to Kovaltry after being on other standard half-life FVIII replacement therapies.

Knowing these therapies’ pharmacokinetic profiles “is vital for a better understanding of the prophylactic regimen in routine prophylaxis and on-demand infusions,” the scientists wrote.

Their study (ChiCTR2000037821) enrolled 47 boys with severe hemophilia A at Beijing Children’s Hospital from August 2019 to September 2020. Of them, 22 switched from Kogenate FS, 14 from Advate, and 11 from GreenMono. All maintained the same dosing regimen after moving to Kovaltry.

Blood samples were taken twice for pharmacokinetic testing: one before switching and the other one after at least three infusions of Kovaltry.

Researchers found that Kovaltry had a longer half-life than Kogenate (14.4 vs. 11.9 hours), Advate (13.4 vs. 9.7 hours), and GreenMono (15.1 vs. 10.7 hours).

Higher blood levels of von Willebrand factor also associated with a longer the half-life for Kovaltry, the researchers reported. And they found that Kovaltry’s half-life was shorter in the 13 boys with blood type O than in those with types A, B, or AB.

“This phenomenon of ‘blood type O’s disadvantage,'” they added, was found in each of the three previous replacement therapy patient groups.

Kovaltry also cleared at a lower rate relative to Kogenate (3.3 vs. 3.9 milliliters per kilogram of body weight per hour, or mL/kg/h), Advate (3.7 vs. 5.9 mL/kg/h), and GreenMono (3.0 vs. 5.1 mL/kg/h).

As a result, the number of boys with a trough level — when a medicine’s concentration in the body is at its lowest level, prior to another dose — of less than 1 international unit per deciliter (<1 IU/dL) fell by about half in each switch group. In turn, “higher trough levels were observed in most participants,” the study noted, and the number of boys with a trough level greater than 3 IU/d doubled, rising from three to six.

“Individuals with the same dosing regimen obtained higher trough levels and less time with low FVIII level in routine prophylaxis,” the researchers wrote.

Looking at the number of bleeds six months before and six months after the switch to Kovaltry, researchers found lower annual bleeding rates after the switch.

The proportion of boys with zero bleeds while on Kovaltry also rose in comparison to when they were on Kogenate (36% vs. 23%), Advate (29% vs. 14%), or GreenMono (18% vs. 10%).

“Participants who switched to Kovaltry from three other FVIII concentrates with the same dosing regimens obtained higher trough FVIII levels and better protection with reduced annualized bleeding rates,” the researchers concluded.

Results also suggested that hemophilia A patients with high blood levels of von Willebrand factor and blood types other than group O “could expect more improvements of PK [pharmacokinetic] profiles and therefore potential reduction in bleeds or longer intervals as well as less frequent infusions,” they added.