AstraZeneca’s Oral Anticoagulant AZD0837 Phase III Program Pushed Back To 2009
This article was originally published in The Pink Sheet Daily
Executive Summary
Backup compound to AstraZeneca’s failed Exanta is being investigated for a stability limitation; Crestor is the only branded statin to increase U.S. market share during 2008.
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AstraZeneca was set to initiate a Phase III program for the oral anticoagulant AZD0837, a backup compound to the U.K. drug maker's failed Exanta , in the fourth quarter, but the program is now delayed until 2009. The setback is due to a stability issue, the company said during its third quarter sales and earning call Oct. 30. The selective and reversible direct thrombin inhibitor is being developed for the prevention of stroke and systemic embolic events in patients with atrial fibrillation. AZD0837 has attracted investor attention as a backup compound to Exanta (ximelagatrain); AstraZeneca discontinued development of Exanta in 2006 after receiving an FDA "not approvable" letter due to liver toxicity. In July, when AstraZeneca announced plans to initiate the Phase III program, management assured investors it had discussed the program with FDA and scrutinized the tolerability and liver effects of AZD0837 (1 (Also see "Learning From Exanta: AstraZeneca Ready For Phase III With ‘0837" - Pink Sheet, 4 Aug, 2008.), p. 14). "The medicines used in Phase III become that on which the registration is based," Chief Financial Officer Simon Lowth explained during the October call. "The batch that is used in Phase III [needs to] meet all of our marketed medicine criteria." Various tests on the Phase III batches for AZD0837 did not meet all of the criteria, he said, noting AstraZeneca is trying to determine the cause. The setback will put AstraZeneca further behind competitors who are also developing oral anticoagulants, including Johnson & Johnson/Bayer, which submitted the Factor Xa inhibitor Xarelto (rivaroxaban) to FDA in July, and Pfizer/Bristol-Myers Squibb's oral Factor Xa inhibitor apixiban in Phase III. In September, AstraZenca announced a setback with its Alzheimer's disease candidate AZD3480 in development with Targacept. The first Phase IIb study for the drug failed to meet its primary endpoint (2 (Also see "Targacept’s AstraZeneca Deal Down, Not Out" - Pink Sheet, 16 Sep, 2008.)). The company is expected to make a decision on future development of the drug in December. U.S. sales of Crestor up 23% in the quarter The earnings call also provided an update on Crestor (rosuvastatin). AstraZeneca is preparing to release full data from the Crestor JUPITER study at the American Heart Association Scientific Sessions Nov. 9. The trial studied the impact of treatment on patients with no evidence of pre-existing cardiovascular disease and low to normal LDL cholesterol but with elevated C-reactive protein, and it was stopped early based on positive data showing "unequivocal evidence" of a reduction in cardiovascular morbidity and mortality among patients treated with Crestor (3 (Also see "Stars Align For AstraZeneca In JUPITER Trial" - Pink Sheet, 31 Mar, 2008.)). As sales of statins like Pfizer's Lipitor and Merck/Schering-Plough's combo pill Vytorin (simvastatin/ezetimibe) have fallen given the efficacy and safety questions around Vytorin and availability of generic Zocor (simvastatin), Crestor sales have remained strong, fueled by new data. The drug was approved for an added indication to slow progression of atherosclerosis in patients with elevated cholesterol last year. Crestor sales jumped 28 percent in the third quarter to $922 million on a constant currency basis, including a 23 percent increase in U.S. sales over the year ago period. It was the only branded statin to increase market share in the U.S. during 2008, the firm reported. Sales of Nexium did not fair as well, down 2 percent to $1.32 billion, driven by an 8 percent decline in the U.S. market. The anti-psychotic Seroquel (quetiapine) generated sales of $1.13 billion in the quarter, up 4 percent over the year ago period. Sales in the U.S. were down 1 percent to $749 million compared to the prior year quarter, which included around $80 million in initial stocking sales for Seroquel XR. FDA approved Seroquel XR on Oct. 10 for the treatment of depressive episodes associated with bipolar disorder, the manic and mixed episodes associated with bipolar I disorder and the maintenance treatment of bipolar I disorder in October. The drug was approved in 2007 for schizophrenia. -Jessica Merrill ([email protected]) |