Data show hemophilia bleeds can be successfully treated while on Hympavzi
Dosing on preventive therapy not affected by breakthrough bleeding, surgery
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- New data show breakthrough bleeds and minor surgeries were successfully managed for hemophilia trial participants on Hympavzi.
- Use of the injection therapy continued without interruption during these events, and drug dosing was not affected.
- Most bleeds were managed with a single factor replacement therapy infusion, an analysis found.
In the large clinical trial that supported the 2024 approval of Hympavzi (marstacimab) for adults and children with hemophilia, use of the prophylactic injection therapy was found to help prevent bleeding episodes. Breakthrough bleeds that did occur, or minor surgical procedures that were needed, were generally effectively treated with standard clotting factor replacement therapy without interrupting the use of Hympavzi.
Those findings, from the Phase 3 BASIS study (NCT03938792), provided the basis for the drug’s approval in the U.S. for individuals 12 and older with hemophilia A or hemophilia B without inhibitors, or neutralizing antibodies that may cause treatment with missing clotting factors to fail.
Now, a new analysis shows that “most acute breakthrough bleeds were managed successfully with a single [factor replacement therapy] infusion, … and dosing requirements were similar before and during [Hympavzi] use.”
According to the researchers, these new data extend the earlier findings on the drug “by providing the first prospective dataset on the real-time management of breakthrough bleeds and [surgery-related] care” when Hympavzi was used as a prophylaxis, or preventive therapy.
The data were detailed in a study titled “Management of breakthrough bleeds and surgical procedures in participants with hemophilia A or B without inhibitors receiving marstacimab prophylaxis in the phase 3 BASIS study,” published in the Journal of Thrombosis and Haemostasis. The work was funded by Pfizer, the therapy’s developer.
Earlier this month, Hympavzi was approved in the European Union for certain patients with inhibitors. This expanded EU approval — the treatment has been approved in Europe since 2024 — was also based primarily on data from BASIS, coming shortly after this new research was published.
Data from BASIS supported Hympavzi approval in US, EU
In hemophilia, the body lacks sufficient functional clotting factors to properly stop bleeding. Patients with hemophilia A are missing factor VIII (FVIII), while those with hemophilia B lack factor IX (FIX). Because of this, bleeding can last longer than normal, and bleeding episodes may occur after an injury or surgical procedure.
Hympavzi is an antibody that blocks the protein TFPI, which normally slows blood clotting. By blocking TFPI, Hympavzi helps the body produce more thrombin, an important clotting factor. This helps blood clot more effectively without needing FVIII or FIX, and thus aids in preventing bleeding.
Before joining the BASIS trial, participants had been followed for a six-month observation period during which they received standard clotting factor replacement therapy. Patients then entered a year-long treatment period in which they received Hympavzi at a starting dose of 300 mg followed by 150 mg, injected under the skin once a week. In total, 116 patients received at least one dose of Hympavzi.
Participants were boys and men, with a median age of 30, and had hemophilia A or B without inhibitors. The researchers studied how often breakthrough bleeds occurred, how they were treated, and how patients managed surgical procedures while on Hympavzi. Many patients already had target joints, meaning joints such as ankles, knees, or elbows that had repeated bleeds over time.
During the treatment period, 88 participants (76%) had at least one episode of bleeding. In total, the researchers recorded 695 bleeds. Around three-quarters of these were treated, while the others were untreated because they were mild or resolved on their own. Most bleeds occurred spontaneously and in joints.
Researchers now focused on acute breakthrough bleeds
For this analysis, the researchers focused on acute breakthrough bleeds. These are episodes of bleeding that occur despite preventive treatment and require clotting factor replacement, the standard treatment in hemophilia, which works by replacing the missing clotting factor in the blood. In this study, 75 patients experienced 453 breakthrough bleeds that required this type of treatment.
Most breakthrough bleeds (83.2%) were controlled with only one infusion of clotting factor. Fewer bleeds required two (14%), three (2%), or four or more infusions (1%). The doses of clotting factor used during treatment with Hympavzi were similar to those normally used before patients started Hympavzi.
This suggests that standard treatment still worked well when needed, according to the researchers.
[Use of Humpavzi] effectively supported management of breakthrough bleeds and minor surgical procedures in participants with hemophilia A or B without inhibitors.
Two boys with hemophilia B experienced traumatic bleeds because they became more physically active and participated in contact sports, the researchers noted. Even in these cases, most bleeds were controlled with one or two infusions of clotting factor replacement. One of these boys later had his weekly dose of Hympavzi increased because the original dose did not provide enough bleeding control.
In total, 14 patients eventually increased their Hympavzi from 150 mg to 300 mg weekly because of ongoing spontaneous bleeding. After the dose increase, a few additional bleeds occurred, but these were generally managed with standard treatment. No serious side effects caused patients to stop treatment after dose escalation.
The study also looked at surgical procedures. A total of 13 patients underwent 15 procedures, including dental work, as well as ear surgery, trigger finger surgery, hernia repair, and treatment for hemorrhoids or wounds. Treatment with Hympavzi was usually continued without stopping, and most surgical procedures were supported with a preventive clotting factor to reduce the risk of bleeding.
While breakthrough bleeds and surgical procedures appeared manageable without stopping Hympavzi, “data on major surgery are lacking due to study exclusions, and conclusions should be restricted to minor and dental procedures,” the researchers wrote. The team said further studies are needed to define perioperative protocols for higher-risk interventions.
The researchers concluded that use of Humpavzi “effectively supported management of breakthrough bleeds and minor surgical procedures in participants with hemophilia A or B without inhibitors.”
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