Novo Nordisk Resumes Phase 3 Clinical Trials of Concizumab for Prophylactic Subcutaneous Treatment in Hemophilia A and B Patients Regardless of Inhibitor Status

August 14, 2020 News /Bio ValleyBIOON/ -- Novo Nordisk recently announced that the Phase 3 clinical trials (EXPLORER 6, 7, and 8) of its hemophilia drug concizumab are resuming. TheseClinical TrialsThe efficacy and safety of subcutaneous concizumab for prophylactic treatment in patients with hemophilia A and hemophilia B, regardless of inhibitor status, are under investigation. The aforementioned trial was suspended in March 2020 due to non-fatal thrombotic events occurring in three patients enrolled in the Phase 3 program.

Novo Nordisk has worked with the relevant authorities to establish a new pathway for concizumab. A new set of safety measures and guidelines, based on an analysis of all available data, has beenFDAConsensus has been reached, and the clinical hold has been lifted.The trial will be resumed as soon as possible once permitted by local procedures.

Concizumab is a first-in-class, high-affinity humanized recombinant monoclonal antibody that inhibits tissue factor pathway inhibitor (TFPI) by binding to the Kunitz-2 domain, enabling the FVIIa:tissue factor complex to generate sufficient activated factor X to restore hemostatic potential in patients with hemophilia. Due to its unique mechanism of action, concizumab is expected to be equally effective in both hemophilia A and B, regardless of inhibitor status. Furthermore, subcutaneous administration may improve adherence, thereby leading to better treatment outcomes. Previously, the United StatesFDAConcizumab has been granted Breakthrough Therapy Designation (BTD) for the treatment of patients with hemophilia B who have inhibitors.

Mechanism of Action of Anti-TFPI Antibodies (Image source: Drugs, volume 78, pages 881–890 (2018))

In July 2019, Novo Nordisk announced positive data from two clinical studies of concizumab at the 27th Congress of the International Society on Thrombosis and Haemostasis (ISTH 2019) held in Melbourne, Australia. The results confirmed the favorable safety profile of concizumab and provided proof-of-concept for its efficacy in preventing bleeding events in patients with hemophilia A (EXPLORER 5 study) and in patients with hemophilia A or B with inhibitors (EXPLORER 4 study). Concizumab was well tolerated in these studies, with no discontinuations due to adverse events and no thromboembolic events observed. Phase II clinical trials showed that the annualized bleeding rate was comparable to that achieved with factor prophylaxis, although many patients were undertreated due to conservative dosing rules. Importantly, no safety concerns were identified regarding the treatment of breakthrough bleeding, and all patients elected to continue into the extension phase of the study.

These Phase II clinical study results support the use of concizumab as a safe and well-tolerated subcutaneous prophylactic therapy in all patients with hemophilia, regardless of inhibitor status. These findings are particularly significant for patients with hemophilia B who have inhibitors, as therapeutic options for this population are limited. Previously,FDAConcizumab has been granted Breakthrough Therapy Designation (BTD) for the treatment of patients with hemophilia B who have inhibitors.

AboutConcizumab Phase III Program：

In October 2019, Novo Nordisk initiated the EXPLORER 7 Phase III clinical trial to evaluate concizumab in patients with hemophilia A and hemophilia B who had developed inhibitors against FVIII or FIX. The objective of this trial was to determine the safety and efficacy of once-daily subcutaneous prophylactic administration of concizumab in reducing the frequency of bleeding events. In November 2019, Novo Nordisk launched a parallel Phase IIIClinical TrialEXPLORER 8 evaluated concizumab in patients with hemophilia A and hemophilia B who did not develop inhibitors. These trials were planned to enroll approximately 293 patients across 32 countries. The trials were suspended in March 2020.(Bioon.com)

Original Source: Novo Nordisk resumes the phase 3 clinical trials investigating concizumab (anti-TFPI mAB) in haemophilia A and B with or without inhibitors