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The US Food and Drug Administration (FDA) has granted fast track designation to betrixaban as extended-duration venous thromboembolism (VTE) prophylaxis for acute medically ill patients.
This includes patients who are hospitalized for serious medical conditions such as heart failure, stroke, infection, and pulmonary disease.
Betrixaban is an investigational oral anticoagulant that directly inhibits the activity of factor Xa.
According to Portola Pharmaceuticals, the company developing betrixaban, the drug has distinct properties that may allow it to demonstrate clinical benefit without significantly increasing the risk of fatal bleeding and certain other serious side effects.
These benefits include a 19- to 25-hour half-life for once-daily dosing, a low peak-to-trough drug concentration ratio that minimizes anticoagulant variability, low renal clearance, and no significant CYP3A4 metabolism, which may reduce the risk of drug-drug interactions.
Betrixaban trials
In the phase 2 Explore-Xa trial, researchers compared betrixaban and warfarin in patients with atrial fibrillation. The team randomized 508 patients to 1 of 3 blinded doses of betrixaban (40 mg, 60 mg, or 80 mg once daily) or unblinded warfarin, adjusted to an international normalized ratio of 2.0-3.0.
The primary outcome was major or clinically relevant non-major bleeding. At a mean follow-up of 147 days, the primary outcome had been met by 1 patient in the 40 mg betrixaban arm, 5 each in the 60 mg and 80 mg betrixaban arms, and 7 in the warfarin arm.
One patient each in the 60 mg and 80 mg arms experienced an ischemic stroke. And there were 2 vascular deaths, 1 each in the 40 mg arm and the warfarin arm.
In the phase 2 EXPERT trial, researchers compared betrixaban and enoxaparin as VTE prophylaxis in patients who underwent total knee replacement.
The team enrolled 215 patients and assigned them to 1 of 3 post-operative prophylaxis regimens: betrixaban at 15 mg twice daily, betrixaban at 40 mg twice daily, or enoxaparin at 30 mg every 12 hours—all for 10 to 14 days.
The primary efficacy outcome was the incidence of VTE during the dosing period, and 175 patients were evaluable for this outcome. VTE occurred in 20% of patients in the 15 mg betrixaban arm (14/70), 15% in the 40 mg betrixaban arm (10/65), and 10% (4/40) in the enoxaparin arm.
Safety outcomes included major and clinically significant non-major bleeds through 48 hours after treatment. There were no bleeds in the 15 mg betrixaban arm, 2 (2.4%) clinically significant non-major bleeds in the 40 mg betrixaban arm, and 1 (2.3%) major bleed and 2 (4.6%) clinically significant non-major bleeds in the enoxaparin arm.
Betrixaban is currently being tested in the phase 3 APEX trial for the prevention of VTE in acute medically ill patients. Portola said it expects to complete enrollment in APEX by the end of this year and report top-line data in the first quarter of 2016.
If the trial is successful, the company plans to submit a new drug application to the FDA later in 2016 under the fast track designation.
About fast track designation
The FDA’s fast track program is designed to facilitate and expedite the development and review of new drugs intended to treat serious or life-threatening conditions and address unmet medical need.
Through the fast track program, a product may be eligible for priority review. In addition, the company developing the drug may be allowed to submit sections of the biologic license application or new drug application on a rolling basis as data become available.
Fast track designation also provides the company with opportunities for more frequent meetings with the FDA to discuss the drug’s development plan and ensure collection of the appropriate data needed to support drug approval. And the designation allows for more frequent written communication from the FDA about things such as the design of proposed clinical trials and the use of biomarkers. 
Image by Kevin MacKenzie
The US Food and Drug Administration (FDA) has granted fast track designation to betrixaban as extended-duration venous thromboembolism (VTE) prophylaxis for acute medically ill patients.
This includes patients who are hospitalized for serious medical conditions such as heart failure, stroke, infection, and pulmonary disease.
Betrixaban is an investigational oral anticoagulant that directly inhibits the activity of factor Xa.
According to Portola Pharmaceuticals, the company developing betrixaban, the drug has distinct properties that may allow it to demonstrate clinical benefit without significantly increasing the risk of fatal bleeding and certain other serious side effects.
These benefits include a 19- to 25-hour half-life for once-daily dosing, a low peak-to-trough drug concentration ratio that minimizes anticoagulant variability, low renal clearance, and no significant CYP3A4 metabolism, which may reduce the risk of drug-drug interactions.
Betrixaban trials
In the phase 2 Explore-Xa trial, researchers compared betrixaban and warfarin in patients with atrial fibrillation. The team randomized 508 patients to 1 of 3 blinded doses of betrixaban (40 mg, 60 mg, or 80 mg once daily) or unblinded warfarin, adjusted to an international normalized ratio of 2.0-3.0.
The primary outcome was major or clinically relevant non-major bleeding. At a mean follow-up of 147 days, the primary outcome had been met by 1 patient in the 40 mg betrixaban arm, 5 each in the 60 mg and 80 mg betrixaban arms, and 7 in the warfarin arm.
One patient each in the 60 mg and 80 mg arms experienced an ischemic stroke. And there were 2 vascular deaths, 1 each in the 40 mg arm and the warfarin arm.
In the phase 2 EXPERT trial, researchers compared betrixaban and enoxaparin as VTE prophylaxis in patients who underwent total knee replacement.
The team enrolled 215 patients and assigned them to 1 of 3 post-operative prophylaxis regimens: betrixaban at 15 mg twice daily, betrixaban at 40 mg twice daily, or enoxaparin at 30 mg every 12 hours—all for 10 to 14 days.
The primary efficacy outcome was the incidence of VTE during the dosing period, and 175 patients were evaluable for this outcome. VTE occurred in 20% of patients in the 15 mg betrixaban arm (14/70), 15% in the 40 mg betrixaban arm (10/65), and 10% (4/40) in the enoxaparin arm.
Safety outcomes included major and clinically significant non-major bleeds through 48 hours after treatment. There were no bleeds in the 15 mg betrixaban arm, 2 (2.4%) clinically significant non-major bleeds in the 40 mg betrixaban arm, and 1 (2.3%) major bleed and 2 (4.6%) clinically significant non-major bleeds in the enoxaparin arm.
Betrixaban is currently being tested in the phase 3 APEX trial for the prevention of VTE in acute medically ill patients. Portola said it expects to complete enrollment in APEX by the end of this year and report top-line data in the first quarter of 2016.
If the trial is successful, the company plans to submit a new drug application to the FDA later in 2016 under the fast track designation.
About fast track designation
The FDA’s fast track program is designed to facilitate and expedite the development and review of new drugs intended to treat serious or life-threatening conditions and address unmet medical need.
Through the fast track program, a product may be eligible for priority review. In addition, the company developing the drug may be allowed to submit sections of the biologic license application or new drug application on a rolling basis as data become available.
Fast track designation also provides the company with opportunities for more frequent meetings with the FDA to discuss the drug’s development plan and ensure collection of the appropriate data needed to support drug approval. And the designation allows for more frequent written communication from the FDA about things such as the design of proposed clinical trials and the use of biomarkers.
Image by Kevin MacKenzie
The US Food and Drug Administration (FDA) has granted fast track designation to betrixaban as extended-duration venous thromboembolism (VTE) prophylaxis for acute medically ill patients.
This includes patients who are hospitalized for serious medical conditions such as heart failure, stroke, infection, and pulmonary disease.
Betrixaban is an investigational oral anticoagulant that directly inhibits the activity of factor Xa.
According to Portola Pharmaceuticals, the company developing betrixaban, the drug has distinct properties that may allow it to demonstrate clinical benefit without significantly increasing the risk of fatal bleeding and certain other serious side effects.
These benefits include a 19- to 25-hour half-life for once-daily dosing, a low peak-to-trough drug concentration ratio that minimizes anticoagulant variability, low renal clearance, and no significant CYP3A4 metabolism, which may reduce the risk of drug-drug interactions.
Betrixaban trials
In the phase 2 Explore-Xa trial, researchers compared betrixaban and warfarin in patients with atrial fibrillation. The team randomized 508 patients to 1 of 3 blinded doses of betrixaban (40 mg, 60 mg, or 80 mg once daily) or unblinded warfarin, adjusted to an international normalized ratio of 2.0-3.0.
The primary outcome was major or clinically relevant non-major bleeding. At a mean follow-up of 147 days, the primary outcome had been met by 1 patient in the 40 mg betrixaban arm, 5 each in the 60 mg and 80 mg betrixaban arms, and 7 in the warfarin arm.
One patient each in the 60 mg and 80 mg arms experienced an ischemic stroke. And there were 2 vascular deaths, 1 each in the 40 mg arm and the warfarin arm.
In the phase 2 EXPERT trial, researchers compared betrixaban and enoxaparin as VTE prophylaxis in patients who underwent total knee replacement.
The team enrolled 215 patients and assigned them to 1 of 3 post-operative prophylaxis regimens: betrixaban at 15 mg twice daily, betrixaban at 40 mg twice daily, or enoxaparin at 30 mg every 12 hours—all for 10 to 14 days.
The primary efficacy outcome was the incidence of VTE during the dosing period, and 175 patients were evaluable for this outcome. VTE occurred in 20% of patients in the 15 mg betrixaban arm (14/70), 15% in the 40 mg betrixaban arm (10/65), and 10% (4/40) in the enoxaparin arm.
Safety outcomes included major and clinically significant non-major bleeds through 48 hours after treatment. There were no bleeds in the 15 mg betrixaban arm, 2 (2.4%) clinically significant non-major bleeds in the 40 mg betrixaban arm, and 1 (2.3%) major bleed and 2 (4.6%) clinically significant non-major bleeds in the enoxaparin arm.
Betrixaban is currently being tested in the phase 3 APEX trial for the prevention of VTE in acute medically ill patients. Portola said it expects to complete enrollment in APEX by the end of this year and report top-line data in the first quarter of 2016.
If the trial is successful, the company plans to submit a new drug application to the FDA later in 2016 under the fast track designation.
About fast track designation
The FDA’s fast track program is designed to facilitate and expedite the development and review of new drugs intended to treat serious or life-threatening conditions and address unmet medical need.
Through the fast track program, a product may be eligible for priority review. In addition, the company developing the drug may be allowed to submit sections of the biologic license application or new drug application on a rolling basis as data become available.
Fast track designation also provides the company with opportunities for more frequent meetings with the FDA to discuss the drug’s development plan and ensure collection of the appropriate data needed to support drug approval. And the designation allows for more frequent written communication from the FDA about things such as the design of proposed clinical trials and the use of biomarkers.