The clinical trials of concizumab, an antibody-based treatment for haemophilia A and B in development at Novo Nordisk, have been put on hold because of safety concerns.
Two phase 3 studies – EXPLORER7 and EXPLORER8 – and a phase 2 study called EXPLORER5 have been halted after non-fatal blood clotting (thrombotic) events were seen in three patients receiving the drug.
All three trials were investigating concizumab prophylaxis in haemophilia A and B patients regardless of whether they had developed ‘inhibitors’ or antibodies to clotting factor drugs – the standard therapy for these disorders.
Novo Nordisk said it had decided to suspend the trials as a precaution and will be talking with regulatory authorities about the next steps for the antibody.
Concizumab is a potential rival to Roche’s blockbuster Hemlibra (emicizumab), the first non-clotting factor therapy for haemophilia A to reach the market, although it targets a different part of the blood clotting pathway.
Novo Nordisk’s drug blocks the activity of tissue factor pathway inhibitor (TFPI), removing a brake on the activation of Factor Xa and – in theory at least – restoring thrombin generation by Factor VIII and Factor IX, which are deficient in haemophilia A and B, respectively.
Hemlibra meanwhile binds to activated Factor IX and Factor X, bridging the two – a function usually carried out by Factor VIII – and allowing coagulation to proceed as normal.
Roche’s drug has transformed the treatment of haemophilia A since its launch in 2017 for patients without inhibitors and the following year for those with inhibitors, racking up sales of around $1.4bn last year, rising more than 500% on 2018.
The drug’s success stems from the fact that it can be administered subcutaneously with various frequencies from once per week to once per month, rather than multiple times per week with clotting factor replacement drugs.
If approved concizumab could rival Hemlibra in haemophilia A, and extend the use of non-clotting factor therapy into haemophilia B, which analysts think could translate into blockbuster sales potential unless it is superseded by one-shot gene therapies coming through development.
The Danish drugmaker was a latecomer to the gene therapy field but has attempted to catch up with an agreement last year with Bluebird Bio focusing on gene-editing drugs for clotting disorders.
Meanwhile, another non-clotting factor drug for haemophilia – Alnylam and Sanofi’s RNA interference candidate fitusiran – is also in late-stage development for haemophilia A and B.