Pradaxa gains new US blood clot approval

Boehringer Ingelheim’s Pradaxa has gained FDA approval for treatment of deep venous thrombosis (DVT) and pulmonary embolism (PE).

The US approval is good news for Boehringer, and comes despite ongoing concerns about the drug’s safety in its other licensed indication, treatment of atrial fibrillation (AF).

In January the FDA announced that it is to undertake a review of existing post-marketing data of the drug in AF patients, comparing its safety and efficacy with standard treatment warfarin.

Clinical trials have shown Pradaxa to have numerous advantages over warfarin – it cuts risk of stroke and blood clots significantly in AF patients compared to the older drug, and has shown lower overall levels of bleeding. However the latest trials in DVT patients have also shown the drug causes higher levels of gastrointestinal bleeding compared to warfarin.

The FDA review of ‘real world’ data from AF patients will address these questions about safety and efficacy, and establish whether or not Pradaxa is performing as well as it did in clinical trials.

New approval

In the meantime, the FDA has decided it could proceed with the approval of Pradaxa’s new licence in DVT and PE.

Pradaxa can now be used in two sets of patients: those with an existing VTE who have been treated with a parenteral anticoagulant for five to 10 days, and secondly in those who no longer have a clot but are being treated to reduce the risk of recurrence.

DVT and PE, collectively referred to as venous thromboembolism (VTE), cause an estimated 900,000 clots per year in the US, with around one-third ending in death.

VTE is the third most common cardiovascular disease after myocardial infarction and stroke. About one-third of patients with VTE will suffer a recurrence within 10 years.

Pradaxa is playing catch up with its biggest rival Xarelto, marketed by Bayer and Johnson & Johnson, which gained a similar licence to treat the condition in November 2012.

Pradaxa’s approval is based on results from four global Phase III studies evaluating its efficacy and safety in treating and preventing the blood clots.

However the data for the drug’s efficacy compared to warfarin is not very compelling – the trials only showed Pradaxa to be non-inferior to warfarin in cutting blood clots. In safety terms, while it produced lower rates overall bleeding, higher rates of gastrointestinal bleeding were seen in those taking Pradaxa.

Resistance to new oral anticoagulants

It is not just Pradaxa experiencing difficulties in the market. All of the new oral anticoagulants (NOACs) Bayer/J&J’s Xarelto, Pfizer/BMS’ Eliquis and Pradaxa are coming up against resistance from doctors reluctant to use them instead of the tried-and-tested treatments, warfarin and aspirin, and low molecular weight heparin. One reason for this is their high cost, but another is a number of safety concerns, including bleeding risk.

In February, Xarelto was rejected for the third time by the FDA after its co-marketers applied once again to market it to prevent heart attacks and strokes in high risk patients with acute coronary syndrome (ACS). FDA reviewers rejected the drug because of problems with the data submission, but also because of doubts about its benefit/risk profile in these patients.

To combat concerns about bleeding risk, Boehringer is developing an antidote to reverse its anti-clotting action. The fully humanised antibody fragment (Fab) is currently in phase I trials.


Xarelto in long-term clot prevention study


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