Concizumab prophylaxis reduces bleeding rates for patients with hemophilia
Click Here to Manage Email Alerts
Key takeaways:
- Concizumab prophylaxis led to lower annualized bleeding rates than no prophylaxis.
- Treatment with concizumab prophylaxis appeared safe, according to investigators.
Concizumab prophylaxis reduced bleeding rates among patients with hemophilia A or B with inhibitors, according to results of the phase 3A explorer7 study published in The New England Journal of Medicine.
Concizumab (Novo Nordisk) prophylaxis also appeared safe, researchers noted.
Rationale and methodology
The individual, complex and changing needs of people with hemophilia means there is no one-size-fits-all treatment approach, according to Tadashi Matsushita, MD, professor in the department of transfusion medicine at Nagoya University Hospital in Japan.
“Each person responds differently to treatment and, therefore, it is important to allow for personalized care, including availability of different treatment options that directly address individual needs,” Matsushita told Healio. “This ensures all people living with hemophilia receive appropriate care throughout their life.
“In addition, some people with hemophilia develop inhibitors — an immune system response to the clotting factors in replacement therapy that means alternative treatment needs to be considered,” Matsushita added. “Development of inhibitors is one of the most critical complications in the treatment of hemophilia today and, for those with hemophilia B, they severely limit treatment options.”
Concizumab is an antitissue factor pathway inhibitor monoclonal antibody created to achieve hemostasis among individuals with all types of hemophilia.
The previous explorer4 trial established proof of concept among those with hemophilia A and hemophilia B with inhibitors.
The prospective, multicenter explorer7 trial included 133 patients, 80 of whom had hemophilia A and 53 of whom had hemophilia B.
Researchers randomly assigned 52 patients to no prophylaxis for at least 24 weeks (group 1, n = 19) or concizumab prophylaxis for at least 32 weeks (group 2, n = 33). They also nonrandomly assigned an additional 81 patients to concizumab prophylaxis for at least 24 weeks.
After temporarily halting treatment due to nonfatal thromboembolic events among three patients assigned concizumab, researchers restarted treatment at a loading dose of 1 mg/kg of body weight, followed by 0.2 mg/kg daily.
Investigators assessed safety, patient-reported outcomes, pharmacokinetics and pharmacodynamics.
Comparison of treated spontaneous and traumatic bleeding episodes in groups 1 and 2 served as the primary outcome.
Findings
Researchers reported mean annualized bleeding rates of 11.8 episodes (95% CI, 7-19.9) among those assigned no prophylaxis for at least 24 weeks vs. 1.7 episodes (95% CI, 95% CI, 1-2.9) among those assigned concizumab prophylaxis for at least 32 weeks (rate ratio = 0.14; 95% CI, 0.07-0.29).
Researchers observed zero bleeding episodes among all patients who received concizumab.
In addition, no reports of thromboembolic events occurred after the restart of treatment, and concizumab plasma concentrations remained stable.
“Overall, adverse events from concizumab were mainly of low grade, and serious events were rare,” researchers wrote. “Before the treatment pause ... one serious thromboembolism (renal infarction) occurred, and two patients had thromboembolism in the concurrent explorer8 trial of concizumab in patients with hemophilia without inhibitors.”
Researchers acknowledged study limitations, including the open-label trial design, unmeasured influence of treatment pause on the results and difficulty gathering sufficient data on patient-reported outcomes.
Implications
The study achieved its primary endpoint, showing a reduction in number of bleeds in the study population.
“These results are encouraging for people living with hemophilia A or B with inhibitors, as well as the hemophilia treating community, as they demonstrate the potential of concizumab to prevent bleeds in a population with complex treatment needs and potentially help to address the significant challenge of inhibitors in hemophilia,” Matsushita told Healio. “Additionally, the treatment of hemophilia often requires IV administration, which can be associated with pain, [be] time consuming, require specific administration skills and may require regular visits to a treatment center. The preference for concizumab prophylaxis reported by participants in the explorer7 study demonstrates the potential for this once-daily subcutaneous treatment to help address the significant daily burden of living with hemophilia.”
It is important to allow for fully personalized care for individuals with hemophilia, Matsushita said. This includes offering different treatment options that directly address individual needs, which may change over time.
“This ensures that all people living with hemophilia receive appropriate care throughout their life,” he said. “Concizumab is currently being investigated across the explorer program across all hemophilia subtypes and is also currently being evaluated in children living with hemophilia A or B with and without inhibitors in the explorer10 study.”
It is reassuring that this first-in-class drug is effective in treating hemophilia A or B with inhibitors, H. Marijke van den Berg, MD, PhD, researcher at Julius Center for Health Sciences and Primary Care in The Netherlands, and Alok Srivastava, MD, FRACP, FRCPA, FRCP, professor of medicine at Christian Medical College in India, wrote in an accompanying editorial.
“Given its reported efficacy in both types of hemophilia without inhibitors, concizumab is evolving as an attractive therapeutic for all patients with hemophilia,” they wrote.
References:
- Marijke van den Berg, H, et al. N Eng Med. 2023;doi:10.1056/NEJMe2304535.
- Matsushita T, et al. N Eng Med. 2023;doi:10.1056/NEJMoa2216455.
For more information:
Tadashi Matsushita, MD can be reached at tmatsu@med.nagoya-u.ac.jp.
Collapse
Read more about
Click Here to Manage Email Alerts