Trial halted for bleeding reduction with abelacimab vs. rivaroxaban in AFib

A phase 2 trial of the investigational factor XI inhibitor abelacimab, used in patients with atrial fibrillation (AFib) who are at moderate to high risk for stroke, has been stopped early due to “an overwhelming reduction” in the primary endpoint – major and clinically relevant nonmajor bleeding – in patients taking abelacimab versus those on rivaroxaban.

The announcement of topline results of the AZALEA-TIMI 71 trial was made by Anthos Therapeutics, the company developing abelacimab.

“The AZALEA-TIMI 71 study is the largest and longest head-to-head study of a Factor XI inhibitor to provide definitive evidence of a highly significant reduction in bleeding as compared to the standard-of-care anticoagulant,” Marc Sabatine, MD, chair of cardiovascular medicine at Brigham and Women’s Hospital and chair of the TIMI study group, both in Boston, stated in the Anthos press release.

“With a median of 21 months of follow-up, spanning more than 2,000 patient years, AZALEA-TIMI 71 represents a landmark study confirming the promise of Factor XI inhibition as causing substantially less bleeding than a current standard-of-care,” Dr. Sabatine added.

Abelacimab is a novel, highly selective, fully human monoclonal antibody with dual inhibitory activity against factor XI and its active form, factor XIa. At the 150-mg dose given subcutaneously once monthly, the drug maintains around 98% inhibition of factor XI, in line with the benign bleeding profile of patients with genetic factor XI deficiency, the company notes.

The AZALEA-TIMI 71 study is an event-driven, randomized study comparing two blinded doses of abelacimab (90 mg or 150 mg given by subcutaneous injection once-monthly) with rivaroxaban 20 mg daily in 1,287 patients with AFib who are at moderate to high risk for stroke. Full results of the study will be presented at an upcoming scientific congress.

Patients in the rivaroxaban arm can transition to abelacimab in an extension study.

In a previous proof-of-concept study published in The New England Journal of Medicine, a single IV dose of abelacimab achieved a large reduction in venous thromboembolism versus enoxaparin in patients undergoing knee surgery.

A phase 3 trial in AFib patients is now planned. The LILAC-TIMI 76 study is an event-driven, randomized trial to evaluate the efficacy and safety of abelacimab relative to placebo on the rate of ischemic stroke or systemic embolism in AFib patients who have been deemed to be unsuitable for currently available anticoagulation therapy. Patients will be randomized to receive abelacimab 150 mg subcutaneously or matching placebo once monthly. The researchers aim to enroll approximately 1,900 patients from North America, Europe, Latin America, the Middle East, and Asia.

Dan Bloomfield, MD, chief medical officer of Anthos Therapeutics, said that, “Abelacimab embodies its promise as a hemostasis-sparing anticoagulant and represents a paradigm shift in the prevention of stroke and other thrombotic conditions.”

It is estimated that 12.1 million people in the United States will have AFib by 2030, but 40%-60% of patients with AFib are not prescribed anticoagulants today, one of the main reasons being concerns about bleeding, the company notes.

“Abelacimab has the potential to provide a game-changing treatment option for all those patients who live with the daily fear of bleeding while taking current anticoagulants,” said Leslie Lake, president of the National Blood Clot Alliance.

Abelacimab has been granted a fast-track designation by the U.S. Food and Drug Administration for the prevention of stroke and systemic embolism in patients with atrial fibrillation.

Several other Factor XI inhibitors are in development and have also shown promising results in terms of a more benign bleeding profile than current standard-of-care anticoagulants.

A version of this article first appeared on Medscape.com.

A phase 2 trial of the investigational factor XI inhibitor abelacimab, used in patients with atrial fibrillation (AFib) who are at moderate to high risk for stroke, has been stopped early due to “an overwhelming reduction” in the primary endpoint – major and clinically relevant nonmajor bleeding – in patients taking abelacimab versus those on rivaroxaban.

The announcement of topline results of the AZALEA-TIMI 71 trial was made by Anthos Therapeutics, the company developing abelacimab.

“The AZALEA-TIMI 71 study is the largest and longest head-to-head study of a Factor XI inhibitor to provide definitive evidence of a highly significant reduction in bleeding as compared to the standard-of-care anticoagulant,” Marc Sabatine, MD, chair of cardiovascular medicine at Brigham and Women’s Hospital and chair of the TIMI study group, both in Boston, stated in the Anthos press release.

“With a median of 21 months of follow-up, spanning more than 2,000 patient years, AZALEA-TIMI 71 represents a landmark study confirming the promise of Factor XI inhibition as causing substantially less bleeding than a current standard-of-care,” Dr. Sabatine added.

Abelacimab is a novel, highly selective, fully human monoclonal antibody with dual inhibitory activity against factor XI and its active form, factor XIa. At the 150-mg dose given subcutaneously once monthly, the drug maintains around 98% inhibition of factor XI, in line with the benign bleeding profile of patients with genetic factor XI deficiency, the company notes.

The AZALEA-TIMI 71 study is an event-driven, randomized study comparing two blinded doses of abelacimab (90 mg or 150 mg given by subcutaneous injection once-monthly) with rivaroxaban 20 mg daily in 1,287 patients with AFib who are at moderate to high risk for stroke. Full results of the study will be presented at an upcoming scientific congress.

Patients in the rivaroxaban arm can transition to abelacimab in an extension study.

In a previous proof-of-concept study published in The New England Journal of Medicine, a single IV dose of abelacimab achieved a large reduction in venous thromboembolism versus enoxaparin in patients undergoing knee surgery.

A phase 3 trial in AFib patients is now planned. The LILAC-TIMI 76 study is an event-driven, randomized trial to evaluate the efficacy and safety of abelacimab relative to placebo on the rate of ischemic stroke or systemic embolism in AFib patients who have been deemed to be unsuitable for currently available anticoagulation therapy. Patients will be randomized to receive abelacimab 150 mg subcutaneously or matching placebo once monthly. The researchers aim to enroll approximately 1,900 patients from North America, Europe, Latin America, the Middle East, and Asia.

Dan Bloomfield, MD, chief medical officer of Anthos Therapeutics, said that, “Abelacimab embodies its promise as a hemostasis-sparing anticoagulant and represents a paradigm shift in the prevention of stroke and other thrombotic conditions.”

It is estimated that 12.1 million people in the United States will have AFib by 2030, but 40%-60% of patients with AFib are not prescribed anticoagulants today, one of the main reasons being concerns about bleeding, the company notes.

“Abelacimab has the potential to provide a game-changing treatment option for all those patients who live with the daily fear of bleeding while taking current anticoagulants,” said Leslie Lake, president of the National Blood Clot Alliance.

Abelacimab has been granted a fast-track designation by the U.S. Food and Drug Administration for the prevention of stroke and systemic embolism in patients with atrial fibrillation.

Several other Factor XI inhibitors are in development and have also shown promising results in terms of a more benign bleeding profile than current standard-of-care anticoagulants.

A version of this article first appeared on Medscape.com.

A phase 2 trial of the investigational factor XI inhibitor abelacimab, used in patients with atrial fibrillation (AFib) who are at moderate to high risk for stroke, has been stopped early due to “an overwhelming reduction” in the primary endpoint – major and clinically relevant nonmajor bleeding – in patients taking abelacimab versus those on rivaroxaban.

The announcement of topline results of the AZALEA-TIMI 71 trial was made by Anthos Therapeutics, the company developing abelacimab.

“The AZALEA-TIMI 71 study is the largest and longest head-to-head study of a Factor XI inhibitor to provide definitive evidence of a highly significant reduction in bleeding as compared to the standard-of-care anticoagulant,” Marc Sabatine, MD, chair of cardiovascular medicine at Brigham and Women’s Hospital and chair of the TIMI study group, both in Boston, stated in the Anthos press release.

“With a median of 21 months of follow-up, spanning more than 2,000 patient years, AZALEA-TIMI 71 represents a landmark study confirming the promise of Factor XI inhibition as causing substantially less bleeding than a current standard-of-care,” Dr. Sabatine added.

Abelacimab is a novel, highly selective, fully human monoclonal antibody with dual inhibitory activity against factor XI and its active form, factor XIa. At the 150-mg dose given subcutaneously once monthly, the drug maintains around 98% inhibition of factor XI, in line with the benign bleeding profile of patients with genetic factor XI deficiency, the company notes.

The AZALEA-TIMI 71 study is an event-driven, randomized study comparing two blinded doses of abelacimab (90 mg or 150 mg given by subcutaneous injection once-monthly) with rivaroxaban 20 mg daily in 1,287 patients with AFib who are at moderate to high risk for stroke. Full results of the study will be presented at an upcoming scientific congress.

Patients in the rivaroxaban arm can transition to abelacimab in an extension study.

In a previous proof-of-concept study published in The New England Journal of Medicine, a single IV dose of abelacimab achieved a large reduction in venous thromboembolism versus enoxaparin in patients undergoing knee surgery.

A phase 3 trial in AFib patients is now planned. The LILAC-TIMI 76 study is an event-driven, randomized trial to evaluate the efficacy and safety of abelacimab relative to placebo on the rate of ischemic stroke or systemic embolism in AFib patients who have been deemed to be unsuitable for currently available anticoagulation therapy. Patients will be randomized to receive abelacimab 150 mg subcutaneously or matching placebo once monthly. The researchers aim to enroll approximately 1,900 patients from North America, Europe, Latin America, the Middle East, and Asia.

Dan Bloomfield, MD, chief medical officer of Anthos Therapeutics, said that, “Abelacimab embodies its promise as a hemostasis-sparing anticoagulant and represents a paradigm shift in the prevention of stroke and other thrombotic conditions.”

It is estimated that 12.1 million people in the United States will have AFib by 2030, but 40%-60% of patients with AFib are not prescribed anticoagulants today, one of the main reasons being concerns about bleeding, the company notes.

“Abelacimab has the potential to provide a game-changing treatment option for all those patients who live with the daily fear of bleeding while taking current anticoagulants,” said Leslie Lake, president of the National Blood Clot Alliance.

Abelacimab has been granted a fast-track designation by the U.S. Food and Drug Administration for the prevention of stroke and systemic embolism in patients with atrial fibrillation.

Several other Factor XI inhibitors are in development and have also shown promising results in terms of a more benign bleeding profile than current standard-of-care anticoagulants.

A version of this article first appeared on Medscape.com.