Boehringer Ingelheim's Investigational Antidote for Pradaxa Receives FDA Breakthrough Therapy Designation

June 26, 2014—Boehringer Ingelheim Pharmaceuticals, Inc. announced that the US Food and Drug Administration (FDA) has granted breakthrough therapy designation to idarucizumab (the company’s proposed international nonproprietary name), an investigational fully humanized antibody fragment that is being studied as a specific antidote for the company’s Pradaxa (dabigatran etexilate mesylate).

Boehringer Ingelheim is planning to pursue an accelerated approval pathway for idarucizumab. The company noted that the breakthrough therapy designation was established by the FDA to help accelerate the development and review of drugs for serious or life-threatening conditions if preliminary clinical evidence indicates the therapy may demonstrate a substantial improvement over existing therapies on one or more clinically significant endpoints. 

The company noted that preclinical studies indicate idarucizumab binds specifically to and inhibits dabigatran with no other expected interactions. Currently, there are no specific antidotes available for newer oral anticoagulants such as Pradaxa. Idarucizumab is still under investigation and has not been approved for clinical use.

According to Boehringer Ingelheim, data from a phase I study presented at the American Heart Association Scientific Sessions in 2013 showed that idarucizumab was able to achieve immediate, complete, and sustained reversal of dabigatran-induced anticoagulation in healthy humans.

The global phase III RE-VERSE AD study is underway in patients taking Pradaxa who have uncontrolled bleeding or require emergency surgery or procedures. European sites are actively enrolling. Currently, no United States sites have been initiated.

In the United States, Pradaxa is approved to reduce the risk of stroke in patients with nonvalvular atrial fibrillation. In April 2014, Boehringer Ingelheim announced in April 2014 that the FDA approved Pradaxa for the treatment of venous thromboembolism, including both deep venous thrombosis (DVT) and pulmonary embolism (PE), in patients who have been treated with a parenteral anticoagulant for 5 to 10 days and to reduce the risk of recurrent DVT and PE.

On June 6, the company announced European approval for Pradaxa for the treatment and prevention of recurrence of DVT and PE in adults.

Pradaxa has been available for more than 6 years and is approved in more than 100 countries with the following indications: to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, primary prevention of venous thromboembolic events in patients undergoing elective total hip replacement surgery, and primary prevention of venous thromboembolic events in patients undergoing elective total knee replacement surgery. Contraindications for Pradaxa include use in patients with a mechanical prosthetic heart valve, active pathological bleeding, and known serious hypersensitivity reaction to Pradaxa.

In December 2014, the company issued a safety update advising that the United States prescribing information for Pradaxa would include a contraindication for mechanical prosthetic heart valves.

The safety and efficacy of Pradaxa in patients with recently implanted bileaflet mechanical prosthetic heart valves was evaluated in the phase II RE-ALIGN trial, which was terminated early because of significantly more thromboembolic events and an excess of major bleeding for Pradaxa compared to warfarin.

Additionally, use of Pradaxa for the prophylaxis of thromboembolic events in patients with atrial fibrillation in the setting of other forms of valvular heart disease, including bioprosthetic heart valve, has not been studied and is not recommended. Pradaxa’s complete prescribing information and usage warnings are available online.