FX activator may help with bleeding control in hemophilia A and B: Trials
Bemiltenase alfa shows promise for patients who've developed inhibitors
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- Bemiltenase alfa, an FX activator, showed promise in early trials for hemophilia A and B patients who have developed inhibitors to treatment.
- The experimental treatment effectively controlled on-demand bleeding, often within two doses.
- Side effects were generally mild, but monitoring for clotting is recommended.
Bemiltenase alfa, an experimental factor X (FX) activator, helped with on-demand bleeding control for people with hemophilia A and B who had developed inhibitors against standard factor replacement therapies, according to results from early clinical trials.
Inhibitors are antibodies that may reduce the effectiveness of hemophilia treatments, making it more difficult to prevent and control bleeds. The researchers called these neutralizing antibodies “a major challenge” in hemophilia care, and noted that they “can reach 30% in severe [hemophilia A] and 5% in severe [hemophilia B] patients.”
As such, “this study marks a significant step forward in developing innovative therapies for this challenging patient population,” the researchers wrote.
Their study, “A specific FX activator for bleeding treatment in hemophilia with inhibitors: multicenter, open-label, phase I/II trials,” was published in Blood Advances. Jiangsu Biojetay Biotechnology, the developer of bemiltenase alfa, sponsored the research and employs one of the paper’s 14 authors.
The early clinical trial results reported in this study support an ongoing Phase 3 trial (NCT06922045), slated to span 18 sites in China. That Phase 3 study is recruiting across several sites and is continuing to test bemiltenase alfa in hemophilia patients with inhibitors.
Inhibitors can reduce effectiveness of hem therapies
A condition marked by excessive bleeding, hemophilia is caused by a deficiency in certain clotting factors, which are proteins that help blood form clots. Hemophilia A is related to problems with factor VIII (FVIII), while hemophilia B is related to a faulty factor IX (FIX). Both result in easy and prolonged bleeding.
Treatment for hemophilia may involve preventive therapies to reduce the risk of bleeding as well as on-demand medicines to help control active bleeding. Factor replacement therapies, which provide a functional version of the missing clotting factor, can play a role in both prevention and control.
However, some people with hemophilia develop inhibitors, or antibodies that target the provided factors. This can reduce the effectiveness of factor replacement.
Limited on-demand treatment options exist for people with inhibitors. Some can cause serious complications, and others may be prohibitively expensive in certain regions, including China. “This highlights the urgent need for the development of novel, effective and more accessible therapies for managing bleeding episodes in these patients,” the researchers wrote.
Bemiltenase alfa was developed to address this gap for people with hemophilia A or B and inhibitors. The medication is made from a purified snake venom-derived protein, which increases blood clotting activity by activating FX. This could help control bleeds without triggering FVIII or FIX inhibitors, according to the developer.
Earlier results from a Phase 1 study showed that small doses of bemiltenase alfa were safe in participants with hemophilia and inhibitors. This prompted follow-up studies, including a Phase 1b/2a trial (NCT05027230) and a Phase 2b trial (NCT06289166).
Bemiltenase alfa successfully controlled bleeding in trials
Across these two studies, 51 participants with hemophilia A or B and inhibitors against factor replacement therapies received bemiltenase alfa. The Phase 1b part of the first trial assessed the treatment’s safety, while both Phase 2 studies assessed its effectiveness in treating bleeding episodes.
During a bleed, participants received intravenous, or into-the-vein, injections of bemiltenase alfa every four hours, with a maximum of six doses.
In the Phase 2a study, bemiltenase alfa successfully controlled bleeding at 94.1% of the sites where participants experienced injuries. The Phase 2b study measured the success rate differently. It found that the medication was effective in 81.9% of bleeding episodes, including episodes with multiple bleeding sites. Performance was similar for bleeding at muscles and joints.
“These findings highlight bemiltenase alfa as a promising new therapeutic option for the treatment of acute bleeding episodes in [hemophilia A or B with inhibitors] patients,” the researchers wrote.
Additionally, 70.9% of bleeding sites in the Phase 2a study and 77.1% of bleeding episodes in the Phase 2b study resolved within two doses of bemiltenase alfa, suggesting that the medication acts quickly. This is important in emergency bleeding situations that require rapid control, according to the researchers.
Throughout the two Phase 2 studies, seven bleeds required additional treatment with a higher dose of bemiltenase alfa or an approved on-demand treatment because the original dose was insufficient.
Regarding safety, the most common events were changes in the levels of certain clotting-related components in blood. This included elevated D-dimers, elevated fibrinogen degradation products, and reduced fibrinogen — all potential signs of abnormal clotting.
Still, “these events were mild, self-resolving, and did not compromise the overall safety profile of bemiltenase alfa,” the researchers wrote.
These findings highlight bemiltenase alfa as a promising new therapeutic option for the treatment of acute bleeding episodes in [hemophilia A or B with inhibitors] patients.
One participant experienced a mild muscle clot that can restrict blood flow, known as deep vein thrombosis, but this did not lead to symptoms and resolved on its own within three months.
Because of the risk of thrombosis, the researchers recommended close monitoring of participants throughout treatment for signs of clots. This could be particularly important for individuals with risk factors for thrombosis, such as obesity, diabetes, or high blood pressure.
Five participants developed antidrug antibodies against bemiltenase alfa, but these did not affect the treatment’s effectiveness.
No trials to date have tested treatment outside China
While these studies support the safety and efficacy of bemiltenase alfa, the researchers noted several limitations, including the small number of participants and relatively short follow-up periods.
“Future investigations with larger cohorts and extended observation periods are needed to further verify the … efficacy and long-term safety of bemiltenase alfa,” the researchers wrote.
No clinical trials to date have tested bemiltenase alfa outside of China. However, the U.S. Food and Drug Administration has designated bemiltenase alfa as an orphan drug for the treatment of hemophilia A and B. This status provides incentives for developing medications to treat rare diseases.
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