Bristol/Pfizer Offer Some Good Apixaban Results, With Key Study Against Warfarin On Track To Report 2H 2011
This article was originally published in Pharmaceutical Approvals Monthly
Executive Summary
Bristol-Myers Squibb/Pfizer got incremental good news and a nice addition to the safety database for their experimental anticoagulant apixaban when a Phase III study was ended early for efficacy at preventing stroke compared to aspirin. The next big read-out for the oral Factor Xa inhibitor, though, will be in the first half of 2011, when results of a major head-to-head contest against warfarin in that setting are due
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Bristol-Myers Squibb/Pfizer got incremental good news and a nice addition to the safety database for their experimental anticoagulant apixaban when a Phase III study was ended early for efficacy at preventing stroke compared to aspirin. The next big read-out for the oral Factor Xa inhibitor, though, will be in the first half of 2011, when results of a major head-to-head contest against warfarin in that setting are due. AVERROES (Apixaban Versus Acetylsalicylic Acid to Prevent Strokes) was stopped after an interim analysis by the study's data monitoring committee showed "clear evidence" of a clinically important reduction in stroke and systemic embolism in 5,600 patients with atrial fibrillation who are not candidates for warfarin, Bristol/Pfizer announced after the markets closed on June 10. The finding may allow the sponsors to seek an initial indication for patients intolerant to or unsuitable for vitamin K antagonist therapy, "a patient population of substantial size," Sanford C. Bernstein analyst Tim Anderson observed in a June 10 note. AVERROES, however, "does not help predict very much" about apixaban's commercial potential, Anderson said. Full AVERROES data will be published in a peer-reviewed journal and presented at a future scientific congress. Patients from both arms will be given the opportunity to continue on apixaban therapy in an open-label extension study. Transitioning the patients in itself suggests a favorable risk/benefit profile, Leerink Swann analyst Seamus Fernandez observed in a June 11 note. Statistical indications are that apixaban may have demonstrated at least a 38 percent relative risk reduction against aspirin, within the range of historical efficacy for warfarin against aspirin, he wrote. Altogether, the Phase III apixaban program - called EXPANSE - comprises nine ongoing or completed Phase III studies involving a projected 60,000 patients in both acute and chronic settings. Key among them is the 18,000-patient ARISTOTLE trial, comparing apixaban and warfarin for prevention of stroke in patients with atrial fibrillation. That trial is expected to report out in the second half of 2011, with a filing anticipated by the end of the year. Anderson predicts sales of apixaban will reach $1.75 billion in 2015. Nonetheless, he points out, the anticoagulant category likely will become crowded, with four direct competitors to apixaban in Phase III and one in Phase II, and indirect competitors entering the field. Differentiation among competitors will be based on a range on intrinsic qualities of the compounds. The efficacy and safety results presented at scientific meetings and published in journals are being scrutinized for any such signals (1 (Also see "Momentum Grows For Novel Oral Anticoagulants Out To Replace Warfarin" - Pink Sheet, 29 Mar, 2010.)). Acute Submissions Await Chronic Indication Data Studies in acute orthopedic settings that might once have primed the indication pump for applications in more lucrative chronic settings, meanwhile, are piling up behind ongoing studies in conditions like acute coronary syndrome and stroke prevention. FDA isn't likely to look first at acute data these days because of the probability the anticoagulant, once approved, would be used off-label in broader chronic applications. After all, the medical community is eager for safer, more convenient anticoagulants - particularly with oral dosing - and with no risk of side effects that require close monitoring. Bayer/Johnson & Johnson's U.S. filing of competing anticoagulant Xarelto (rivaroxaban) for acute use in knee and hip replacement surgery, for example, was met with a "complete response" from FDA in May 2009. The agency asked to see surveillance data from other countries where the drug, also an oral Factor Xa inhibitor, is approved, and for other information, but requested no new studies. Bayer/J&J, however, are waiting to submit data on prevention of stroke in patients with atrial fibrillation along with their response on the acute indication (2 (Also see "Bayer/J&J Will Resubmit Xarelto For Acute Indication In Second Half, Along With New Application For Chronic Use" - Pink Sheet, 1 Mar, 2010.)). Data from their head-to-head study of rivaroxaban against warfarin in stroke prevention, the ROCKET-AF study, are due in the second half, and the filing/resubmission is anticipated shortly thereafter. For apixaban, data from the third study in Bristol/Pfizer's ADVANCE series, comparing apixaban to Sanofi-Aventis' low molecular weight heparin Lovenox (enoxaparin) in prevention of venous thromboembolism in patients undergoing orthopedic surgery - this one in hip replacement - are to be presented in July at the International Congress on Thrombosis in Milan. Apixaban failed to prove non-inferior to enoxaparin in ADVANCE I, which followed the so-called North American dosing regimen in knee replacement patients, but proved superior in ADVANCE II in knee surgery, which used European dosing (3 (Also see "Bristol/Pfizer's Apixaban Bests Lovenox At Preventing VTE In Second Attempt" - Pink Sheet, 1 Mar, 2010.)). A European filing for apixaban in prevention of VTE in adults who have undergone elective hip or knee replacement was accepted by EMA in March. - Shirley Haley ( 4 [email protected] ) |