Boehringer scores trial success for Pradaxa antidote
pharmafile | June 29, 2015 | News story | Research and Development, Sales and Marketing | Boehringer, Pradaxa, idarucizumab
Bosses at Boehringer Ingelheim say the latest results of a study of idarucizumab, and antidote for its blockbuster blood-thinner Pradaxa, should quell lingering concerns about the safety of the drug.
Pradaxa (dabigatran) was the first in a new class of anticoagulants to be approved, and offers comparable blood-thinning effects to warfarin without the need for ongoing monitoring.
But these drugs have been dogged by safety concerns after reports of severe and in some cases fatal bleeding in patients taking these treatments. An antidote for Pradaxa and other new oral anticoagulants would be clinically useful in situations where they cause a patient to bleed too much, or uncontrollably.
Idarucizumab is a monoclonal antibody fragment that works by binding to dabigatran – the active molecule in Pradaxa – in the blood, 350 times more strongly than thrombin, a natural enzyme in the blood that promotes clotting.
Therefore it binds to dabigatran and neutralises its activity in the body, reversing its effects and stopping bleeding in people undergoing surgery or who have suffered falls, accidents or traumatic injuries.
Boehringer had presented earlier Phase I results at the American Society of Hematology conference in San Francisco. The latest interim analysis of results from on ongoing prospective trial of idarucizumab, which reverses the blood-thinning effects of dabigatran, in 90 patients who either were in hospital and either had life-threatening bleeding or who required surgery.
Patients in the study were an average of 77 years old and being treated with Pradaxa for stroke prevention. The real-world study included patients with comorbidities who are often excluded from clinical trials.
Idarucizumab restored blood clotting back to normal within a few minutes in between 88 and 98% of patients given the treatment, and kept levels of the blood-thinning compound in Pradaxa at low levels for 24 hours in 79% of patients. However some 21 patients had serious adverse events during the study, including haemorrhages.
It follows a small, Phase I study in 47 healthy volunteers published in The Lancet. It found that idarucizumab worked in a dose-dependent manner with seven people reporting mild side effects (swelling and hot flushes).
Boehringer has already submitted idarucizumab for approval in Canada, and in the US and Europe, where the drug has been granted expedited reviews. The company is planning a further analysis of idarucizumab in 300 patients worldwide.
Professor Jörg Kreuzer, vice president medicine, in Boehringer’s cardiovascular therapy area, told Pharmafile the latest results would support the German firm’s applications.
“The results of REVERSE-AD were overwhelmingly positive. Nearly 100% of patients were able to competently reverse their anticoagulation and bring the, back to normal coagulation – this in itself is a breakthrough results for us. It really confirms all the data we have been regenerating in our Phase I trials, which indicated complete reversal of dabigatran activity would be possible.
“It’s a specific antidote that will only act on dabigtran, which should make it easier for physicians to treat patients who have either an emergency bleed or are schedule for emergency surgery. This will clearly reshape the way patients on dabigatran who are experiencing some kind of emergency will be treated in the future.”
Professor Kreuzer added the availability of an effective antidote could offer BI an advantage in a class of drugs still suffering a negative perception of bleeding risk.
“At the time we gained approval for dabigatran we were so confident [of its safety and efficacy] that the drug could be marketed without an antidote on hand. But there are lingering concerns [about Pradaxa’s safety].
“The antidote does address some of those concerns. But the data from trials shows the risk of a bleed or death when on dabigatran is much lower than the risk that comes with warfarin. Having an antidote means the perception will become better, but the data clearly indicates that dabigatran is a safer drug than warfarin.”
Novo Nordisk presents ISTH data
The Boehringer study was published in the New England Journal of Medicine and at presented the International Society of Thrombosis and Haemostasis 2015 Congress in Toronto, Canada. At the same conference, Novo Nordisk presented results from its Phase III trial of, NovoEight (turoctocog alfa) for the prevention and treatment of bleeds in people with severe haemophilia A.
The interim data found treatment with Novo Eight resulted in an overall estimated median annual bleeding rate (ABR) of 1.56 when used as a preventive treatment, and 90% of all bleeding episodes were successfully treated with one or two infusions of Novo Eight.
“These interim results provide an extension to the body of evidence supporting the long-term use of Novo Eight,” says Dr Margaret Ozelo, from the University of Campinas in Sao Paulo, Brazil, and study investigator.
“For people with haemophilia A, finding treatments that are effective at preventing bleeding episodes long-term is essential.”
Lilian Anekwe
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