Novo Nordisk Halts Three Hemophilia Clinical Trials of Concizumab Due to Non-Fatal Thrombotic Events

By Fan Dongdong

Novo Nordisk Announces Suspension of Three Ongoing Conizumab Clinical Trials Due to Safety ConcernsRecently, Novo Nordisk announced the suspension of three ongoing clinical trials of conizumab due to safety concerns. Previously, Novo Nordisk had been evaluating the efficacy and safety of conizumab for the treatment of hemophilia A and B.

The halted studies include two Phase III trials (EXPLORER 7 and EXPLORER 8) and one Phase II trial (EXPLORER 5). Novo Nordisk stated that the decision to pause was based on non-fatal thrombotic events occurring in three patients during the Phase III trials. Currently, Novo Nordisk is working with an independent data monitoring committee to evaluate existing trial data to determine whether the thrombotic issues are related to the drug.

Hemophilia is an inherited blood disorder characterized by low levels of clotting factor proteins in patients. When these protein levels are low, the patient’s blood cannot clot effectively. Concizumab is a high-affinity, humanized recombinant monoclonal antibody that inhibits tissue factor pathway inhibitor (TFPI) by binding to its Kunitz-2 domain, thereby allowing the FVIIa–tissue factor complex to generate sufficient activated Factor X to restore hemostatic potential in patients with hemophilia. Furthermore, the subcutaneous administration of Concizumab helps improve patient adherence.

In October 2017, Novo Nordisk initiated the EXPLORER 5 clinical study, which enrolled 36 patients and aimed to evaluate the efficacy and safety of conizumab in reducing bleeding episodes in patients with hemophilia A. The primary treatment observation period was 24 weeks, followed by an extension phase of 52 weeks. In October and November 2019, Novo Nordisk sequentially launched the EXPLORER 7 and 8 clinical studies to assess the efficacy and safety of conizumab in the treatment of hemophilia A and B.

Following this suspension, no new patients will be enrolled until the trial risks and a new plan are determined, and currently enrolled subjects will temporarily discontinue conizumab treatment.

As a major player in the diabetes market, Novo Nordisk has been actively expanding into the hemophilia market. In February 2020, the company launched Esperoct, a treatment for hemophilia A, in the United States. This drug is a recombinant, extended half-life factor VIII replacement therapy.

In October 2019, Novo Nordisk and bluebird bio entered into a collaboration agreement to jointly develop next-generation gene-editing therapies for genetic disorders, including hemophilia. The three-year agreement primarily focuses on the collaborative development of gene therapy for Hemophilia A. Reportedly, this partnership will leverage bluebird bio’s mRNA-based megaTAL technology to edit or insert specific gene segments, ultimately achieving therapeutic outcomes.

Reference Source: Novo Nordisk Pauses Three Clinical Trials Because of Non-Fatal Thrombotic Events