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Biotech Tracker:  Exanta Continues to Move Forward
November 06, 2003 Francis, et al will present results from AstraZeneca’s (NYSE: AZN) Exanta development program at the plenary session of the American Society of Hematology meetings in San Diego next month. The data further contribute to the massive investigational support for Exanta as a clinically relevant oral anticoagulant for use in the management of venous thromboembolic disorders. We estimate Exanta’s probability of FDA approval at greater than 90%.

Exanta convenience advantage lies in its fixed-dose, oral protocol. This convenience will be reduced, but not eliminated, by a liver enzyme-tracking requirement. Exanta’s ability to compete with both low molecular weight heparins such as enoxaparin (Aventis’s [NYSE: AVE] Lovenox) and warfain formulations (Bristol-Myers Squibb’s [NYSE: BMY] Coumadin) has been significantly enhanced by these and other recent results.

The study to be presented at ASH is an international, randomized, double-blind, double placebo-controlled trial evaluated 2,489 patients with acute deep vein thrombosis (DVT), of whom 37% presented with a confirmed pulmonary embolism (PE). The subjects were randomized to receive either Exanta 36 mg twice daily for 6 months, or subcutaneous enoxaparin 1 mg/kg twice daily for a minimum of 5 days followed by warfarin (requiring blood monitoring) for 6 months. The goal of this program was to determine whether Exanta is noninferior to standard enoxaparin/warfarin (enoxaparin is often used in lieu of unfractionated heparin in the initial management strategy) in the prevention of recurrent venous thromboembolism (VTE) at 6 months.

Exanta was administered to 1,240 patients. Enoxaparin/warfarin was administered to 1,249 patients. The data support Exanta’s noninferiority in this clinical scenario.

Clinical outcome Exanta
n (% )
Enoxaparin / warfarin
n (% )
Absolute difference
Exanta - enoxaparin/warfarin
% (95% CI)
Recurrent VTE (ITT)

 26 (2.1)

24 (2.0)

+0.2 ( 1.0; +1.3)

Recurrent VTE (OT)

23 (2.0)

17 (1.5)

+0.5 ( 0.6; +1.6)

Major bleeding (OT)

14 (1.3)

26 (2.2)

1.0 ( 2.1; +0.1)

Recurrent VTE and/or major bleeding (OT)

37 (3.2)

43 (3.7)

0.5 ( 2.0; +1.0)

All-cause mortality (ITT)

28 (2.3)

42 (3.4)

1.1 ( 2.4; +0.2)

All-cause mortality (OT)

7 (0.7)

10 (0.9)

0.2 ( 1.0; +0.5)

Estimated cumulative risk; rounded figure; CI = confidence interval; ITT = intention-to-treat; OT = on-treatment

Exanta’s association with a disproportionately increased incidence of serum alanine aminotransferase (ALT) elevation (9.6 of Exanta recipients versus 2.0% of enoxaparin/warfarin recipients) was observed.

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