Drugs Xagena
Eliquis ( Apixaban ) is an oral selective Factor Xa inhibitor. By inhibiting Factor Xa, a key blood clotting protein, Apixaban decreases thrombin generation and blood clot formation.
Eliquis is approved to reduce the risk of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation ( NVAF ) in the United States, European Union, Japan and in other countries.
Eliquis is approved for the prophylaxis of venous thromboembolism ( VTE ) in adult patients who have undergone elective hip or knee replacement surgery in the United States, European Union and other countries. Eliquis is not approved for this indication in Japan.
Eliquis is approved for the treatment of deep vein thrombosis ( DVT ) and pulmonary embolism ( PE ), and prevention of recurrent DVT and PE in the European Union. Eliquis is not approved for this indication in the United States.
a) In the AMPLIFY trial, Eliquis was shown to be non-inferior for the treatment of recurrent venous thromboembolism / venous thromboembolism-related death and was statistically superior in the primary safety endpoint of major bleeding versus Enoxaparin / Warfarin.
In the AMPLIFY-EXT trial, Eliquis has demonstrated a superior reduction in venous thromboembolism / all-cause death with no statistical difference in major bleeding events versus placebo.
In the AMPLIFY study a total of 5,395 patients were randomized to treatment with Apixaban 10 mg twice daily orally for seven days followed by Apixaban 5 mg twice daily orally for six months, or Enoxaparin 1 mg/kg twice daily subcutaneously for at least five days ( until INR greater than or equal to 2 ) and Warfarin ( target INR range 2.0-3.0 ) orally for six months.
The mean age was 56.9 years and 89.8% of randomized patients had unprovoked VTE events.
In the study, Apixaban was shown to be non-inferior to Enoxaparin / Warfarin in the combined primary endpoint of adjudicated recurrent symptomatic venous thromboembolism ( nonfatal deep vein thrombosis or nonfatal pulmonary embolism ) or VTE-related death.
Apixaban efficacy in initial treatment of venous thromboembolism was consistent between patients who were treated for a pulmonary embolism [ relative risk, RR=0.9 ] or DVT [ RR=0.8 ].
Efficacy across subgroups, including age, gender, body mass index ( BMI ), renal function, extent of index PE, location of DVT thrombus, and prior parenteral Heparin use was generally consistent.
For patients randomized to Warfarin, the mean percentage of time in therapeutic range ( TTR ) ( INR 2.0-3.0 ) was 60.9. The effect of Apixaban on recurrent symptomatic VTE or VTE- related death was consistent across the different levels of center TTR; within the highest quartile of TTR according to center, the relative risk for Apixaban vs Enoxaparin / Warfarin was 0.79.
The primary safety endpoint was major bleeding. In the study, Apixaban was statistically superior to Enoxaparin / Warfarin in the primary safety endpoint [ RR=0.31; P-value less than 0.0001 ].
The adjudicated major bleeding and clinically relevant non-major ( CRNM ) bleeding at any anatomical site were generally lower in the Apixaban group as compared to the Enoxaparin / Warfarin group.
Adjudicated International Society on Thrombosis and Haemostasis ( ISTH ) major gastrointestinal bleeding occurred in 6 ( 0.2% ) Apixaban-treated patients and 17 ( 0.6% ) Enoxaparin / Warfarin-treated patients.
b) In the AMPLIFY-EXT study a total of 2,482 patients were randomized to treatment with Apixaban 2.5 mg twice daily orally, Apixaban 5 mg twice daily orally, or placebo for 12 months after completing six to 12 months of initial anticoagulant treatment. Of these, 836 patients ( 33.7% ) participated in the AMPLIFY study prior to enrollment in the AMPLIFY-EXT study.
The mean age was 56.7 years and 91.7% of randomized patients had unprovoked VTE events.
In the study, both doses of Apixaban were statistically superior to placebo in the primary endpoint of symptomatic, recurrent VTE ( nonfatal deep vein thrombosis or nonfatal pulmonary embolism ) or all-cause death.
Apixaban efficacy for prevention of a recurrence of a VTE was maintained across subgroups, including age, gender, BMI, and renal function.
The primary safety endpoint was major bleeding during the treatment period. In the study, the incidence in major bleeding for both Apixaban doses was not statistically different from placebo.
There was no statistically significant difference in the incidence of major, clinically relevant non-major, minor, and all bleeding between the Apixaban 2.5 mg twice daily and placebo treatment groups.
The recommended dose of Apixaban for the prevention of recurrent deep vein thrombosis and pulmonary embolism is 2.5 mg taken orally twice daily.
Adjudicated ISTH major gastrointestinal bleeding occurred in 1 ( 0.1% ) Apixaban-treated patient at the 5 mg twice daily dose, no patients at the 2.5 mg twice daily dose, and 1 ( 0.1% ) placebo-treated patient. ( Xagena )
Source: BMS & Pfizer, 2014
XagenaMedicine_2014
