In Trial, Hemlibra Improves Joint Health for Younger Hem A Patients

The study of the hemophilia A treatment found most success in ages 18 to 40

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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A man is shown holding an elbow that clearly is hurting him.

Treatment with Hemlibra (emicizumab) improved joint health in people with hemophilia A participating in the Phase 3 HAVEN 3 trial, with the most pronounced improvements seen in those younger than 40 or in patients who had joints with frequent bleeds.

Findings were detailed in the study “Effect of emicizumab prophylaxis on bone and joint health markers in people with haemophilia A without factor VIII inhibitors in the HAVEN 3 study,” published in the journal Haemophilia. The work was funded by Roche, which markets Hemlibra.

Hemlibra is a bispecific antibody that can functionally replace factor VIII (FVIII), the clotting factor that is missing in hemophilia A. Clinical trial data have demonstrated the treatment can prevent bleeds and improve life quality for patients, but the effect of Hemlibra on bone and joint health — often a problem for people with hemophilia — has not been thoroughly explored.

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Here, a team led by scientists at Roche conducted an analysis of data from HAVEN 3 (NCT02847637), one of the clinical trials that tested the safety and effectiveness of prophylactic (preventive) Hemlibra treatment in people with hemophilia A, with the goal of evaluating patients’ bone and joint health.

Most participants were treated with Hemlibra throughout the study, while a subset received no prophylactic treatment for the first 24 weeks before they were allowed to switch to Hemlibra prophylaxis.

The analysis included data on 152 patients with a mean age of 38.3 years. About half (48%) had previously been on prophylactic replacement therapies. Over two-thirds (67.1%) had at least one target joint, and about 5% had a diagnosis of osteoporosis. Target joints were major joints (hip, elbow, wrist, shoulder, knee, and ankle) in which three or more bleeds occurred in the six months before study entry.

None of the patients in HAVEN 3 had FVIII inhibitors, or neutralizing antibodies targeting FVIII.

The analysis focused primarily on patients’ hemophilia joint health score (HJHS). As the name suggests, HJHS is a hemophilia-specific measure of joint health, with higher scores indicating more severe symptoms.

Joint health on Hemlibra

At the study’s start, HJHS scores were generally higher (worse) for patients who had target joints or were older. After nearly a year (49 weeks), the mean HJHS in the total group decreased (improved) by 1.86 points.

“The impact of [Hemlibra] prophylaxis was generally consistent across individual joints, although the knee joints were the most responsive and demonstrated slightly greater improvement,” the researchers wrote.

Further analyses showed that, among patients with target joints, mean HJHS decreased by 2.28 points after 49 weeks, whereas no significant change was seen for those without target joints. Better improvements were also seen for patients who had not been on prophylactic treatment.

“Participants had better joint health and function if they were previously on prophylaxis before switching to [Hemlibra] and had no target joints at baseline; therefore, these groups had less opportunity for improvement,” the researchers wrote.

For patients ages 12 to 39 years, a mean HJHS improvement of 3.22 points was seen at 49 weeks, whereas no significant change was seen for older patients (ages 40 and older). The team speculated that this may be because prophylactic therapy cannot reverse joint damage that has already accrued in older patients.

Available data suggested that these trends remained consistent out to 96 weeks (about two years).

Analyses of bone-related biomarkers from 117 patients with available data generally did not show any significant changes after over a year on Hemlibra prophylaxis.

“Surrogate biomarkers of bone and joint health did not show significant changes over the first 72 weeks of [Hemlibra] prophylaxis. This may reflect the effects on the measured biomarkers by factors other than joint health such as age and physical activity,” the researchers wrote. They noted that patients’ biomarker levels were broadly similar to what are seen in people without hemophilia, “with little possibility to demonstrate improvement.”

A noted limitation of this study is that most participants were adults over 18 years old. Researchers highlighted a need for further research to explore how Hemlibra treatment affects bone and joint health during childhood and adolescence, which are important periods of bone growth.

“Additional data are needed to better understand the long-term effect of [Hemlibra] prophylaxis on bone and joint health in [people with hemophilia A], especially those starting [Hemlibra] at a young age,” they wrote.