Kovaltry Safe and Effective Prophylactic for Hemophilia A, Long-term Study Shows

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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AMT-061, Phase 3 trial data

Preventive treatment with Kovaltry (octocog alfa) is safe and effective at preventing bleeds, including joint bleeds, for up to two years in people with hemophilia A, a long-term extension study shows.

Findings were reported in the study “BAY 81-8973 demonstrated efficacy, safety and joint status improvement in patients with severe haemophilia A in the LEOPOLD I extension for ≤2 years” published in the European Journal of Haematology.

In hemophilia A, a mutation in the gene coding clotting factor VIII (FVIII) makes patients prone to bleeds in soft tissues, muscles, and joints. To prevent bleeding and minimize joint damage, intravenous (into-the-vein, IV) injections of FVIII are recommended as standard treatment.

Kovaltry, developed by Bayer and formerly known as BAY 81-8973, is a recombinant human coagulation FVIII that has been approved for prophylactic (preventive) treatment of  adults and children with hemophilia A since 2016 in Europe, and in the U.S. and Canada.

Kovaltry’s approval was based on data from LEOPOLD trials, including LEOPOLD 1 (NCT01029340), LEOPOLD 2 (NCT01233258), and LEOPOLD Kids (NCT01311648).

Data from the Phase 3 LEOPOLD 1 trial showed that Kovaltry was safe and effective at preventing and treating bleeding episodes in 62 adults and adolescents with severe hemophilia A who were followed for one year.

Patients (61 in total) who completed the trial were invited to continue treatment for an additional year in an open-label extension study that aimed to assess the treatment’s long-term efficacy and safety.

In total, 55 people (ages 12–61) continued with treatment in the open-label extension study (EudraCT: 2009-012149-43), and 43 (78.2%) of them completed another year of treatment.

Kovaltry doses were not changed between the LEOPOLD 1 and the extension study. Patients received prophylactic treatment two or three times weekly. The median dose used to treat bleeds was 34.2 IU per kilogram per infusion.

For those previously using on-demand treatment (20%), the median number of bleeds was 36, and four  for those previously on treatment prophylactically. From a total of 154 bleeds, 23 (14.9%) were considered severe by study participants.

Results also showed that 32.7% of patients did not experience bleeding episodes during the extension study, an increase from the 23.6% reported in the original trial. Researchers also observed a tendency for fewer spontaneous bleeds, which dropped from 64.9% in LEOPOLD 1 to 52.7% in the extension study.

Long-term treatment with Kovaltry also reduced the rate of joint bleeds on target joints from 90.9% in the first trial to 60% in the extension study.

Better bleeding control was also achieved. The number of days before the first bleeding event increased from 39.5 days in the original trial to 82.3 days during the open-label extension.

Good or excellent responses to Kovaltry were reported in 77.4% of the cases. Additionally, five major surgeries were performed during the extension study, and surgeons classified hemostasis (the body’s response to blood vessel damage and hemorrhage) as excellent or good.

Good health-related quality of life seen in patients at the LEOPOLD 1’s start (median of 78.1 points in Haemo-QoL-A) was maintained over the course of its extension study (median of 79.8 points at the end of first year; 79.0 points at the end of second year).

Overall, 37 patients experienced 88 adverse events during the extension study. Most were mild or moderate, with four events in three patients thought possibly related to Kovaltry. These included seasonal allergy, itches, and a heart attack. The 62-year-old patient with the heart attack had “known multiple cardiovascular risk factors,” the study reported, and was treated at a hospital.

“Over the course of 2 years, bleeding rates, severity, and characteristics either remained stable or improved, with a decrease in spontaneous bleeds observed over time, and a decrease in the proportion of joint bleeding episodes affecting target joints, indicating improved joint protection compared to the pivotal study,” the researchers wrote.

These findings confirm the “suitability of BAY 81-8973 for long-term treatment,” they added.