From the Journals

Experts opine on hemophilia treatments



The hemophilia A treatment paradigm has shifted away from simply maintaining a prophylaxis trough level of 1% towards a focus on patient outcomes and leading healthy, active lives, according to a recent report in The Journal of Medicine in Life.

To get there, the World Federation of Hemophilia (WFH) has recognized that physicians need to aim for higher trough levels so patients can lead as normal a life as possible, but there’s debate about which levels are ideal.

“There is increasing recognition and evidence from the literature that factor trough levels of 1%-3% are insufficient to prevent bleeds in all patients with hemophilia. It has also been suggested that maintaining higher factor levels (above 10%) may be optimal to prevent subclinical bleeding and the gradual progression of joint disease over a lifespan in very active patients,” according to the report.

The paper was a summary of expert opinion on the issue and a range of other current and future challenges in hemophilia care. Switzerland-based Sobi surveyed nine hemophilia experts in central Europe for their insights, then convened an advisory panel to flesh out their responses.

They were asked for their thoughts on the efficacy of factor versus non-factor replacement therapy when aiming for a 3%-5% target trough for hemophilia A prophylaxis.

About half said non-factor therapy was more effective, while the other half favored factor therapy because it has similar efficacy and allows the tailoring of treatment to individual pharmacokinetic data, physical activity, and the condition of the musculoskeletal system.

However, “if the new treatment aim for [prophylaxis] is to increase the trough level, existing and future prophylactic regimens are likely to require adjustment. Maintaining such high trough levels in some patients may lead to the re-shortening of longer treatment intervals and, consequently, an increase of previously reduced factor consumption, which has been an important benefit of [extended half-life] products,” the report noted.

“This creates space for next-generation FVIII replacement therapy,” such as Sobi’s efanesoctocog alfa, which has been granted fast-track designation in the United States for hemophilia treatment, the report notes.

There was also a split in opinion on whether factor therapy offered similar or improved efficacy, compared with non-factor therapy when prophylaxis is intensified to aim for a 10% trough in very active patients. Factor prophylaxis “may be preferable for active hemophilia A” because of the greater personalization, it said.

The experts noted that trough levels are just one aspect of patient care; the overall aim is a better quality of life. The panel was asked about how quality of life could be enhanced in the future. More than half said that the move towards personalized treatment is key, including greater use of telemedicine applications such as Sobi’s florio HAEMO and Takeda’s MyPKFit.

“In addition, most of the experts agreed that novel therapies such as the new class of FVIII replacement therapy, efanesoctocog alfa (BIVV001), would become another mainstream therapy due to its potential to achieve personalized, extended protection against all bleeding types in patients with severe hemophilia A,” the report said.

In the meantime, the advent of extended half-life products and novel non-factor therapies such as emicizumab; subcutaneous siRNA prophylactic therapies such as fitusiran; and anti-tissue factor pathway inhibitors such as marstacimab – each with different mechanisms of action – has led to new challenges in laboratory monitoring.

For more personalized treatment to happen, “it will be necessary for specialized clinical laboratories to be fully equipped with the required equipment, product-specific reagents, and expertise to perform appropriate assays and monitor levels of coagulation activity,” the report noted.

Thrombin generation assays to measure the dynamics of blood coagulation are promising. “There’s significant potential for monitoring the efficacy” of prophylaxis across various established and novel hemophilia treatments, but the approach “is still in its infancy,” the report noted.

Overall, “new and emerging therapies such as novel [extended half-life] factor concentrates and non-factor treatments will likely reshape hemophilia care within the next decade, providing more efficacious and convenient management options and possibly curative therapies,” it said.

The work was funded by Sobi. Most of the panelists disclosed speaker/advisor fees and/or research funding from the company, as well as many others.

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