Investigators Report Progress on New Subcutaneous Therapy

Results from a pair of phase 2 clinical trials of the investigational subcutaneous therapy, Concizumab were presented at the recent XXVII Congress of the International Society on Thrombosis and Haemostasis (ISTH), which took place July 6-10, 2019 in Melbourne, Australia. Concizumab, which is developed using a synthetically produced (recombinant) antibody derived from a single cell clone, is designed to be equally effective in individuals with hemophilia A and B, irrespective of inhibitor status.

Concizumab is unique in that it does not function like a traditional factor product by replacing, through intravenous infusion, deficient proteins such as factor VIII (FVIII) or factor IX (FIX). Instead, upon subcutaneous injection, a laboratory-engineered monoclonal antibody initiates a series of chemical and molecular reactions that generates enough of activated factor X, in vivo, to restore proper clotting. The technology would enable clinicians to forgo FVIII or FIX replacement, while still restoring effective hemostasis in hemophilia A or B patients.

Developed by Novo Nordisk, the therapy is being investigated for the prevention of bleeding episodes in hemophilia A patients, and in hemophilia A/B patients with inhibitors. The trials are known as Explorer4 and Explorer5.

Explorer4 is a randomized, controlled phase 2 trial including 26 patients with hemophilia A/B, with inhibitors. Explorer5 is a phase 2 trial in 36 patients with hemophilia A, without inhibitors. According to a recent press release, treatment with concizumab was well tolerated with no adverse event-related withdrawals and no thromboembolic events. The trials also showed annualized bleeding rates that were comparable to trial participants who were treated with an existing factor replacement product. Lastly, 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 a paper published in Blood which described the findings.

“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.

Global phase 3 trials are slated to begin later in 2019.

Source: Pipeline Review, July 8, 2019

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