October 18, 2019
4 min read

Concizumab effective, safe for certain patients with hemophilia

You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

We were unable to process your request. Please try again later. If you continue to have this issue please contact customerservice@slackinc.com.

Concizumab appeared safe and demonstrated clinical proof of concept in preventing bleeds among patients with hemophilia A and hemophilia A or B with inhibitors, according to results of two phase 2 trials published in Blood.

“The current standard of prophylactic therapy in individuals with hemophilia A and B is administration of a therapeutic agent that suppresses or prevent bleeding episodes. For most patients this has involved the administration of a specific clotting factor concentrate intravenously on a regular schedule designed to convert them from a severely deficient state to a moderately or mildly deficient state,” Amy D. Shapiro, MD, pediatric hematologist-oncologist and CEO and co-medical director of Indiana Hemophilia & Thrombosis Center, told HemOnc Today. “For individuals who have moderate or mild hemophilia A or B, prophylaxis may be administered prior to times of activity, or prior to planned interventions that place them at increased risk for bleeding. Either activity based or interventional-based prophylaxis may be shorter or longer term based upon the activity or intervention and resultant need for healing and rehabilitation.”

Concizumab (Novo Nordisk), a high-affinity, anti-tissue factor pathway inhibitor monoclonal antibody, is in development for subcutaneous treatment of patients with hemophilia. It allows the body to generate adequate amounts of factor Xa to ensure effective hemostasis.

In the two phase 2 trials, Shapiro and colleagues analyzed the effectiveness and tolerability of daily concizumab prophylaxis among patients with hemophilia A or B with inhibitors and hemophilia A without inhibitors.

In the multicenter explorer4 trial, researchers randomly assigned 26 patients with hemophilia A or hemophilia B with inhibitors to receive concizumab (n = 17) or activated recombinant factor VII (NovoSeven RT, Novo Nordisk; n = 9).

The single-arm, multicenter explorer5 trial included 36 patients with hemophilia A without inhibitors who received concizumab.

Effectiveness of concizumab in preventing bleeding episodes, determined by annual bleeding rate (ABR) at the last dose level, served as the primary endpoint of both trials. Safety and immunogenicity served as secondary endpoints.

Among all hemophilia A patients in both trials, 21 (58.3%) remained on the initial concizumab dose of 0.15 mg/kg, seven (19.4%) increased to 0.2 mg/kg and eight (22.2%) increased to 0.25 mg/kg.

When assessing the last dose level of each patient in explorer4, researchers observed 47 treated bleeding episodes among 15 patients (88%) in the concizumab prophylaxis group in the main part of the trial, with an estimated ABR of 4.5 (95% CI, 3.2-6.4) vs. 20.4 (95% CI, 14.4-29.1) in the activated recombinant factor VII on-demand group (median ABR, 4.5 vs. 19.7)


The ABR ratio of 0.22 (95% CI, 0.13-0.36) between the treatment groups demonstrated proof of concept because it was less than 1, researchers noted.

Researchers observed a similar proportion of spontaneous bleeds (51%) and traumatic bleeds (49%) in the concizumab group, with an estimated spontaneous ABR of 2.3 (95% CI, 1.4-3.6). Almost three-quarters (72%) of the bleeds occurred in joints, with an estimated joint ABR of 3.2 (95% CI, 2.2-4.7). Researchers did not characterize any bleeds as severe.

In explorer5, 70 treated bleeding episodes occurred among 23 patients (63.9%) during the main part of the trial, for an estimated ABR of 7 (95% CI, 4.6-10.7) and median ABR of 4.5, which demonstrated clinical proof of concept because the 95% CI was less than 12.

Spontaneous bleeds occurred less often than traumatic bleeds (37% vs. 61%), with an estimated spontaneous ABR of 2.5 (95% CI, 1.5-4.3). More than half of bleeds (63%) occurred in joints; estimated joint ABR was 4.9 (95% CI, 2.8-8.5). Researchers assessed three bleeding episodes as severe.

No severe adverse events, adverse event-related withdrawals or thromboembolic events occurred with concizumab.

These results supported the additional research of concizumab as a prophylactic treatment for patients with hemophilia, Shapiro told HemOnc Today.

“Further phase 3 studies are planned/underway and designed to evaluate efficacy and safety,” she said. “The most critical population for which exist unmet needs are the factor IX-deficient patients with inhibitors. In addition, concizumab could serve as an alternative to treatment with clotting factor concentrates in factor IX deficiency without an inhibitor, or indeed for those patients with hemophilia A with or without inhibitors.

“The availability of a novel agent such as concizumab for patients with hemophilia B either with or without an inhibitor, can serve to expand the current treatment armamentarium thereby advancing care and improving outcomes,” Shapiro added. –by John DeRosier

For more information:

Amy Shapiro, MD, can be reached at ashapiro@ihtc.org.

Disclosures: Shapiro reports no relevant financial disclosures. Please see the study for all authors’ relevant financial disclosures.