FDA News Release

FDA approves Praxbind, the first reversal agent for the anticoagulant Pradaxa
Praxbind approved for specific emergency situations


October 16, 2015

The U.S. Food and Drug Administration today granted accelerated approval to Praxbind (idarucizumab) for use in patients who are taking the anticoagulant Pradaxa (dabigatran) during emergency situations when there is a need to reverse Pradaxa’s blood-thinning effects.  
“The anticoagulant effects of Pradaxa are important and life-saving for some patients, but there are situations where reversal of the drug’s effects is medically necessary,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Today’s approval offers the medical community an important tool for managing patients taking Pradaxa in emergency or life-threatening situations when bleeding can’t be controlled.”

The FDA approved Pradaxa in 2010 to prevent stroke and systemic blood clots in patients with atrial fibrillation, as well as for the treatment and prevention of deep venous thrombosis and pulmonary embolism. Praxbind is the first reversal agent approved specifically for Pradaxa and works by binding to the drug compound to neutralize its effect. Praxbind solution is for intravenous injection.

The safety and effectiveness of Praxbind were studied in three trials involving a total of 283 healthy volunteers taking Pradaxa (i.e., people who did not require an anticoagulant). In the healthy volunteers who were given Praxbind, there was an immediate reduction in the amount of Pradaxa in participants’ blood (measured as unbound dabigatran plasma concentration) that lasted for a period of at least 24 hours. In this study, the most common side effect from use of Praxbind was headache.

Another trial included 123 patients taking Pradaxa who received Praxbind due to uncontrolled bleeding or because they required emergency surgery. In this ongoing trial, based on laboratory testing, the anticoagulant effect of Pradaxa was fully reversed in 89 percent of patients within four hours of receiving Praxbind. In this patient trial, the most common side effects were low potassium (hypokalemia), confusion, constipation, fever and pneumonia.

Reversing the effect of Pradaxa exposes patients to the risk of blood clots and stroke from their underlying disease (such as atrial fibrillation). The Praxbind labeling recommends patients resume their anticoagulant therapy as soon as medically appropriate, as determined by their health care provider.

Praxbind is approved under the FDA’s accelerated approval program, which allows the agency to approve drugs for serious conditions that fill an unmet medical need based on an effect on a surrogate or an intermediate clinical endpoint that is reasonably likely to predict a clinical benefit to patients. The program is designed to provide patients with earlier access to promising new drugs, but the company will be required to submit additional clinical information after approval to confirm the drug’s clinical benefit.

Praxbind and Pradaxa are both marketed by Boehringer Ingelheim of Ridgefield, Connecticut.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

NEJM Journal Watch



Antidote to Dabigatran Is Approved
NEWS IN CONTEXT | ONCOLOGY AND HEMATOLOGYGENERAL MEDICINE INFORMING PRACTICE

October 22, 2015

Antidote to Dabigatran Is Approved
David Green, MD, PhD
Idarucizumab quickly nullifies the anticoagulant effect of dabigatran.

Dabigatran (Pradaxa) is an oral anticoagulant approved for treating patients who have atrial fibrillation or venous thromboembolism. The most important adverse effect of the drug is bleeding, but a specific antidote to reverse this anticoagulant has not been available previously.

On October 16, 2015, the U.S. FDA approved idarucizumab (Praxbind), a monoclonal antibody fragment that binds tightly to dabigatran and nullifies its anticoagulant activity. Approval was based on data from a randomized, placebo-controlled trial in healthy volunteers and a study of patients requiring urgent reversal because of bleeding or need for a surgical procedure (JW Oncol Hematol Aug 2015 and Lancet 2015; 386:680). In addition, in an ongoing, open-label trial of patients with life-threatening or uncontrolled bleeding or who require emergency surgery or urgent procedures, 89% of 123 enrollees exhibited complete reversal of dabigatran within 4 hours of receiving idarucizumab.

COMMENT

Four new oral anticoagulant drugs currently are available in the U.S: Three inhibit coagulation factor Xa, and one — dabigatran — is a thrombin inhibitor. Major bleeding with these drugs generally has been less common than with vitamin K antagonists such as warfarin, but prescribers must be able to rapidly reverse their anticoagulant activity when dangerous bleeding or drug overdosing occurs, or when patients require urgent surgery. Clinicians now can infuse idarucizumab to bind dabigatran, and an antidote (andexanet alfa) for the factor Xa–inhibiting drugs currently is in clinical trials.



http://www.jwatch.org/na39428/2015/10/22/antidote-dabigatran-approved?query=etoc_jwonchem&jwd=000013047244&jspc=