Feature | Antiplatelet and Anticoagulation Therapies | May 07, 2018

FDA Clears First Reversal Agent for Rivaroxaban, Apixaban Anticoagulants

FDA designated this agent as a break-through treatment of patients hospitalized with life-threatening bleeding who take factor Xa drugs

The U.S. Food and Drug Administration (FDA) has approved Portola Pharmaceuticals' Andexxa, the first antidote indicated for patients treated with rivaroxaban (Xarelto) and apixaban (Eliquis), when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding.

The U.S. Food and Drug Administration (FDA) has approved Portola Pharmaceuticals' Andexxa, the first antidote indicated for patients treated with rivaroxaban (Xarelto) and apixaban (Eliquis), when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding.

 

Figure 1: The approval of Andexxa was supported by data from two Phase 3 ANNEXA studies (ANNEXA-R and ANNEXA-A), which evaluated the safety and efficacy of the drug in reversing the anticoagulant activity of the factor Xa inhibitors rivaroxaban and apixaban. This chart shows the reversal response for rivaroxaban.

Figure 1: The approval of Andexxa was supported by data from two Phase 3 ANNEXA studies (ANNEXA-R and ANNEXA-A), which evaluated the safety and efficacy of the drug in reversing the anticoagulant activity of the factor Xa inhibitors rivaroxaban and apixaban. This chart shows the reversal response for rivaroxaban.

Figure 2: The approval of Andexxa was supported by data from two Phase 3 ANNEXA studies (ANNEXA-R and ANNEXA-A), which evaluated the safety and efficacy of the drug in reversing the anticoagulant activity of the factor Xa inhibitors rivaroxaban and apixaban. This chart shows the reversal response for apixaban.

Figure 2: The approval of Andexxa was supported by data from two Phase 3 ANNEXA studies (ANNEXA-R and ANNEXA-A), which evaluated the safety and efficacy of the drug in reversing the anticoagulant activity of the factor Xa inhibitors rivaroxaban and apixaban. This chart shows the reversal response for apixaban.

 

 

May 7, 2018 — The U.S. Food and Drug Administration (FDA) has approved Portola Pharmaceuticals' Andexxa, the first factor Xa inhibitor antidote indicated for patients treated with rivaroxaban (Xarelto) and apixaban (Eliquis), when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding.

Andexxa (coagulation factor Xa [recombinant], inactivated-zhzo) received both U.S. orphan drug and FDA breakthrough therapy designations and was approved under the FDA's accelerated approval pathway based on the change from baseline in anti-factor Xa activity in healthy volunteers. Continued approval for this indication may be contingent upon post-marketing study results to demonstrate an improvement in hemostasis in patients.

"Today's approval represents a significant step forward in patient care and one that the medical community has been eagerly anticipating," said Stuart J. Connolly, M.D., ANNEXA-4 Executive Committee chairman and professor in the Department of Medicine of the Faculty of Health Sciences at McMaster University in Hamilton, Ontario. "Andexxa's rapid reversal of the anticoagulating effects of rivaroxaban and apixaban will help clinicians treat life-threatening bleeds, where every minute counts."

The use of factor Xa inhibitors is rapidly growing because of their efficacy and safety profile compared to enoxaparin and warfarin in preventing and treating thromboembolic conditions such as stroke, pulmonary embolism and venous thromboembolism (VTE). This growth has come with a related increase in the incidence of hospital admissions and deaths related to bleeding, the major complication of anticoagulation. In the U.S. alone in 2016, there were about 117,000 hospital admissions attributable to factor Xa inhibitor-related bleeding and nearly 2,000 bleeding-related deaths per month. 

"The expansion of available reversal agents for people prescribed newer oral anticoagulant therapies is crucial," said Randy Fenninger, chief executive officer of the National Blood Clot Alliance, a patient-led, voluntary health advocacy organization. "The availability now of a reversal agent specific to rivaroxaban and apixaban expands choice and enables patients and providers to consider these treatment options with greater confidence."

Portola expects to launch Andexxa under an Early Supply Program with Generation 1 product in early June. Broader commercial launch is anticipated in early 2019 upon FDA approval of its Generation 2 manufacturing process.

The Marketing Authorization Application (MAA) for andexanet alfa is also under review by the European Medicines Agency. The Committee for Medicinal Products for Human Use (CHMP) communicated a positive trend vote on the MAA in February 2018. A formal opinion from the CHMP is expected by the end of 2018, and the European Commission is expected to issue a decision in early 2019.

 

Clinical Data for Andexxa
The approval of Andexxa is supported by data from two Phase 3 ANNEXA studies (ANNEXA-R and ANNEXA-A) published in The New England Journal of Medicine,[1] which evaluated the safety and efficacy of Andexxa in reversing the anticoagulant activity of the factor Xa inhibitors rivaroxaban and apixaban in healthy volunteers (Figure 1 and Figure 2, respectively). As described in the label, results demonstrated that Andexxa rapidly and significantly reversed anti-factor Xa activity (the anticoagulant mechanism of these medicines). The median decrease in anti-Factor Xa activity from baseline was 97 percent for rivaroxaban and 92 percent for apixaban.

Interim data from the ongoing ANNEXA-4 single-arm, open-label study in patients with major bleeding also were assessed by the FDA as part of its review and approval. Data from 185 evaluable patients showed that Andexxa rapidly and significantly reversed anti-Factor Xa activity when administered as a bolus and sustained this reversal when followed by a 120-minute infusion. The median decrease from baseline was 90 percent for rivaroxaban and 93 percent for apixaban.

The FDA post-marketing requirement is a clinical trial that randomizes patients to receive either Andexxa or usual care (the type of care the enrolling institution would provide in the absence of Andexxa). This study is scheduled to be initiated in 2019 and be reported in 2023.

 

Related Content on New Oral Anti-coagulants (NOACs):

Drug Stops Dangerous Bleeding in Patients Taking Factor Xa Inhibitors

Advantages and Disadvantages of Novel Oral Anticoagulants

Rollout of New Oral Anticoagulants Will Drastically Change Clinical Practice

Questions Remain on DAPT Prolongation

 
For more information: www.andexxa.com

 

Reference: 

1. Deborah M. Siegal, John T. Curnutte, Stuart J. Connolly, et al. Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity. N Engl J Med 2015; 373:2413-2424. DOI: 10.1056/NEJMoa1510991. 

 

Related Content

Fragmin (dalteparin sodium) injection was cleared by the FDA for use in pediatric patients. It was initially approved by the FDA in 1994 for adults and is a type of heparin.

Fragmin (dalteparin sodium) injection is now cleared by the FDA for use in pediatric patients. It was initially approved by the FDA in 1994 for adults and is a type of heparin.

Technology | Antiplatelet and Anticoagulation Therapies | May 17, 2019
May 17, 2019 — The U.S.
PhaseBio Receives FDA Breakthrough Therapy Designation for Ticagrelor Reversal Agent
Technology | Antiplatelet and Anticoagulation Therapies | April 30, 2019
PhaseBio Pharmaceuticals Inc. announced the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy...
People With Heart Disease at Risk When Pharmacies Close
News | Antiplatelet and Anticoagulation Therapies | April 24, 2019
April 24, 2019 — New research from the University of Illinois at Chicago shows that when pharmacies close, people sto
Study Finds Only Six Percent of Patients Taking Statins as Directed
News | Antiplatelet and Anticoagulation Therapies | April 18, 2019
A recent study found patients with atherosclerotic cardiovascular disease cut their risk of a second major adverse...
HonorHealth Research Institute Launches SynIVUS-DAPT Study
News | Antiplatelet and Anticoagulation Therapies | April 16, 2019
HonorHealth Research Institute announced the first patients have been enrolled in the SynIVUS-DAPT Study. The clinical...
Lack of Physician Guidance, Fear of Side Effects Influence Statin Compliance
News | Antiplatelet and Anticoagulation Therapies | April 15, 2019
Despite national guidelines indicating statins can lower risk of heart attack and stroke, many patients who could...
Stopping DAPT After One Month Improved Outcomes in Stent Patients
News | Antiplatelet and Anticoagulation Therapies | March 25, 2019
Patients who stopped taking aspirin one month after receiving a stent in the heart’s arteries but continued taking the...
Apixaban Effective in Specific Cohort of Non-Valvular Atrial Fibrillation Patients
News | Antiplatelet and Anticoagulation Therapies | March 19, 2019
The Bristol-Myers Squibb-Pfizer Alliance announced results from the Phase 4 AUGUSTUS trial evaluating Eliquis (apixaban...
Researchers Develop Reversible, Drug-Free Antiplatelet Therapy
News | Antiplatelet and Anticoagulation Therapies | February 19, 2019
A new reversible, drug-free antiplatelet therapy could reduce the risk of blood clots and potentially prevent cancer...
FDA Approves Portola Pharmaceuticals' Prior Approval Supplement for Andexxa Generation 2 Manufacturing Process
News | Antiplatelet and Anticoagulation Therapies | January 02, 2019
The U.S. Food and Drug Administration (FDA) has approved Portola Pharmaceuticals’ Prior Approval Supplement (PAS) for...
Overlay Init