MELBOURNE, Australia I July 8, 2019 I– Concizumab demonstrated a favourable safety profile and clinical proof of concept for the prevention of bleeding episodes in patients with haemophilia A (explorer5) and haemophilia A/B with inhibitors (explorer4). Results from the main phase (24 weeks) of the two phase 2 trials were presented today at the 27th International Society on Thrombosis and Haemostasis (ISTH) Congress by Professor Astermark, Skåne University Hospital, Malmø, Sweden. A manuscript describing results of the trials has been submitted to the journal Blood.
Treatment with concizumab was well tolerated, with no adverse event-related withdrawals and no thromboembolic events. The phase 2 trials show annual bleeding rates comparable to factor prophylaxis despite many patients being undertreated due to conservative dosing rules. Importantly, no safety concerns with breakthrough-bleed treatment were observed and all patients chose to continue to the ongoing extension phases of the trials.
“These results are particularly important for patients with haemophilia B and inhibitors, for whom treatment options are limited, as underscored by the FDA having granted concizumab Breakthrough Therapy Designation for the treatment of haemophilia B with inhibitors,” said Amy Shapiro, investigator in the explorer4 trial and lead author of the paper in Blood.
“We are delighted that the results from the concizumab phase 2 trials support its use as a safe and well-tolerated subcutaneously administered prophylactic therapy in all patients with haemophilia, regardless of inhibitor status, and we are excited to proceed with phase 3,” said Ludovic Helfgott, executive vice president of Novo Nordisk Biopharm Operations. The global phase 3 programmes will be initiated later this year.
About the explorer4 and explorer5 trials
Explorer4 is a randomised controlled phase 2 trial in 26 patients with haemophilia A/B and inhibitors, and explorer 5 is a phase 2 trial in 36 patients with haemophilia A. Patients in explorer4 were randomised 2:1 to prophylaxis with concizumab or on-demand treatment with eptacog alfa activated (recombinant activated factor VII [rFVIIa]). Based on the knowledge collected during the phase 2 trials, which included a conservative efficacy-based individual dose escalation regimen, an optimised dose and trial design has been developed for the phase 3 pivotal trials.
About concizumab
Concizumab is a first-in-class, high-affinity, humanised, recombinant monoclonal antibody that inhibits TFPI (tissue factor pathway inhibitor) by binding to its Kunitz-2 domain, allowing the FVIIa:tissue factor complex to generate enough activated factor X to restore the haemostatic potential of the haemophilia patients. Due to its unique mechanism of action, concizumab is expected to be equally effective in haemophilia A and B, irrespective of inhibitor status. Furthermore, its subcutaneous administration could potentially lead to improved adherence and therefore better outcomes 1.
About haemophilia
Haemophilia is a rare and serious condition caused by either factor VIII (haemophilia A) or factor IX (haemophilia B) deficiency. Many affected individuals remain undiagnosed or inadequately treated. Even when treated, those affected may suffer from chronic pain and limited mobility, mainly due to episodic bleeding in the joints, and if undertreated or not treated at all, are at risk of dying at a young age. A significant unmet medical need for a safe and effective therapeutic agent that can be administered subcutaneously in the prophylactic setting remains for many haemophilia patients.
References
1. Møller Nielsen AZ, G.; Friderichsen, P. Switching from syringe-to-vial to a prefilled subcutaneous pen injector in haemophilia – as easy as ABC? Haemophilia. 2017;23(Supplement S2):37 (abs P015).
SOURCE: Novo Nordisk
Post Views: 43
MELBOURNE, Australia I July 8, 2019 I– Concizumab demonstrated a favourable safety profile and clinical proof of concept for the prevention of bleeding episodes in patients with haemophilia A (explorer5) and haemophilia A/B with inhibitors (explorer4). Results from the main phase (24 weeks) of the two phase 2 trials were presented today at the 27th International Society on Thrombosis and Haemostasis (ISTH) Congress by Professor Astermark, Skåne University Hospital, Malmø, Sweden. A manuscript describing results of the trials has been submitted to the journal Blood.
Treatment with concizumab was well tolerated, with no adverse event-related withdrawals and no thromboembolic events. The phase 2 trials show annual bleeding rates comparable to factor prophylaxis despite many patients being undertreated due to conservative dosing rules. Importantly, no safety concerns with breakthrough-bleed treatment were observed and all patients chose to continue to the ongoing extension phases of the trials.
“These results are particularly important for patients with haemophilia B and inhibitors, for whom treatment options are limited, as underscored by the FDA having granted concizumab Breakthrough Therapy Designation for the treatment of haemophilia B with inhibitors,” said Amy Shapiro, investigator in the explorer4 trial and lead author of the paper in Blood.
“We are delighted that the results from the concizumab phase 2 trials support its use as a safe and well-tolerated subcutaneously administered prophylactic therapy in all patients with haemophilia, regardless of inhibitor status, and we are excited to proceed with phase 3,” said Ludovic Helfgott, executive vice president of Novo Nordisk Biopharm Operations. The global phase 3 programmes will be initiated later this year.
About the explorer4 and explorer5 trials
Explorer4 is a randomised controlled phase 2 trial in 26 patients with haemophilia A/B and inhibitors, and explorer 5 is a phase 2 trial in 36 patients with haemophilia A. Patients in explorer4 were randomised 2:1 to prophylaxis with concizumab or on-demand treatment with eptacog alfa activated (recombinant activated factor VII [rFVIIa]). Based on the knowledge collected during the phase 2 trials, which included a conservative efficacy-based individual dose escalation regimen, an optimised dose and trial design has been developed for the phase 3 pivotal trials.
About concizumab
Concizumab is a first-in-class, high-affinity, humanised, recombinant monoclonal antibody that inhibits TFPI (tissue factor pathway inhibitor) by binding to its Kunitz-2 domain, allowing the FVIIa:tissue factor complex to generate enough activated factor X to restore the haemostatic potential of the haemophilia patients. Due to its unique mechanism of action, concizumab is expected to be equally effective in haemophilia A and B, irrespective of inhibitor status. Furthermore, its subcutaneous administration could potentially lead to improved adherence and therefore better outcomes 1.
About haemophilia
Haemophilia is a rare and serious condition caused by either factor VIII (haemophilia A) or factor IX (haemophilia B) deficiency. Many affected individuals remain undiagnosed or inadequately treated. Even when treated, those affected may suffer from chronic pain and limited mobility, mainly due to episodic bleeding in the joints, and if undertreated or not treated at all, are at risk of dying at a young age. A significant unmet medical need for a safe and effective therapeutic agent that can be administered subcutaneously in the prophylactic setting remains for many haemophilia patients.
References
1. Møller Nielsen AZ, G.; Friderichsen, P. Switching from syringe-to-vial to a prefilled subcutaneous pen injector in haemophilia – as easy as ABC? Haemophilia. 2017;23(Supplement S2):37 (abs P015).
SOURCE: Novo Nordisk
Post Views: 43
