No more patients will be enrolled in the trials and current treatment “will cease” while they determine the risks and plans for the trials.
Denmark’s Novo Nordisk paused three clinical trials of concizumab over safety issues. The trials are evaluating the drug for hemophilia A and B. No more patients will be enrolled in the trials and current treatment “will cease” while they determine the risks and plans for the trials.
Two of the trials were the EXPLORER 7 and EXPLORER 8 Phase III trials. The other was the Phase II EXPLORER 5 trial. The company indicates the decision was based on non-fatal thrombotic events in three patients enrolled in the Phase III program. The company and an independent Data Monitoring Committee are evaluating the data to determine if the problems are linked to the drug.
“While it is disappointing to pause the trials, patient safety is of utmost important to Novo Nordisk—both for those taking part in our clinical trials and those who use our products on a daily basis,” said Mads Krogsgaard Thomsen, executive vice president and chief science officer of Novo Nordisk. “Together with relevant authorities, we will now carefully evaluate all available data and decide how to best move forward.”
Hemophilia is an inherited blood disorder characterized by low levels of clotting factor proteins that help blood clot appropriately. When these proteins are at low levels, patients’ blood does not clot effectively, which can lead to serious health issues when bleeding happens. The two most common forms of hemophilia are hemophilia A and B, named after the specific clotting factors that the patients are missing or are in insufficient amounts.
Thrombosis refers to a blood clot, which can lead to stroke or other health problems.
Concizumab is a monoclonal antibody against Tissue Factor Pathway Inhibitor (TFPI).
EXPLORER 7 and EXPLORER 8 were designed to demonstrate that concizumab can prevent bleeds in the body and the drug’s safety. Patients who typically only take medicine to treat bleeds on demand were randomized to either receive concizumab at the beginning of the study while the other group continued to receive their normal therapy and received concizumab after six months. The drug was injected by the patient every day subcutaneously via a pen-injector.
EXPLORER 5, the Phase II trial, involved 36 patients, and was being conducted in Asia, Europe and the U.S. The treatment duration is 24 weeks in the main phase and 52 weeks in the extended phase.
Novo Nordisk is a major player in the diabetes market but has been aggressively moving into hemophilia. The company launched Esperoct in the U.S. for hemophilia A in February 2020. Esperoct is a recombinant extended half-life factor VIII replacement therapy. It was approved by the U.S. Food and Drug Administration (FDA) in 2019 based on five multinational trials, which included 270 patients.
“At Novo Nordisk, we have a longstanding commitment to the hemophilia community, beginning with the development of our first recombinant factor therapy more than 30 years ago,” said Pia D’Urbano, corporate vice president, Biopharmaceuticals, Novo Nordisk, at the time of launch. “We recognize that people with rare bleeding disorders need multiple therapy options and are proud to now make Esperoct available as a new treatment option for those living with hemophilia A, the most common form of the chronic bleeding disorder.”
In October 2019, Novo Nordisk and Cambridge, Massachusetts-based bluebird bio entered a collaboration deal to develop next-generation genome editing therapies for genetic diseases, including hemophilia. It is a three-year pact, with the top priority to develop a gene therapy for hemophilia A. It will leverage bluebird’s mRNA-based megaTAL technology that is used to silence, edit, or insert genetic components.
