* Last week, the AVERROES trial, sponsored by Bristol-Myers Squibb (BMY) and Pfizer (PFE), was stopped early due to apixaban’s clear therapeutic benefit over aspirin for stroke prevention in atrial fibrillation (SPAF).
* Although the AVERROES results are good news for apixaban, the ongoing ARISTOTLE trial is significantly more important to the outlook of the oral factor Xa inhibitor. ARISTOTLE compares apixaban to warfarin, the current drug of first choice for SPAF.
* We were increasing apixaban’s inThought approvability index (IAI) score in SPAF to 58%(C) from 40%(C). The IAI uses historical approval rates and detailed analysis of clinical trials to model the probability of approval. The letter grade indicates relative progress in the current phase in apixaban’s case, an average likelihood of advancing to timely regulatory review.
* Boehringer Ingelheim’s dabigatran continues to be the frontrunner in the race to displace warfarin as the drug of choice for the chronic management of SPAF. Dabigatran’s IAI score is 80%(A).
Apixaban’s (Pfizer, Bristol-Myers Squibb) therapeutic triumph over aspirin in the AVERROES (Apixaban versus Acetylsalicylic Acid to Prevent Strokes, n=5,600) trial is a small but important victory for the developmental oral anticoagulant. It suggests that the agent at least has potential to vie for stroke prevention in atrial fibrillation (SPAF) market share for those in whom Coumadin (warfarin) is not an acceptable therapeutic choice.
AVERROES success is implied by its having been stopped early. A predefined interim analysis by the independent Data Monitoring Committee revealed clear evidence of a clinically important reduction in stroke and systemic embolism.
Apixaban’s safety profile, compared to aspirin, also was said to have been clinically acceptable in this program (apixaban 5mg versus aspirin 81-324mg for up to 36 months or end study). AVERROES’s primary endpoint is time from first dose to first occurrence of ischemic stroke, hemorrhagic stroke, or systemic embolism. Secondary endpoints were time to first occurrence of ischemic stroke, hemorrhagic stroke, systemic embolism, myocardial infarction, or vascular death. The results of AVERROES will likely be presented and published in high profile meetings and journals in the coming months.
Apixaban’s performance in ARISTOTLE (NCT00412984, warfarin-controlled, n=18,183, enrollment completed last month) will be the ultimate clinical determinant of the drug's potential to maximize SPAF market share. The factor Xa inhibitor has generated mixed results versus Lovenox in venousthromboembolism settings. It has demonstrated a suspect benefit to risk ratio, primarily related to bleeding-related harm, in acute coronary syndrome settings.
Anticipating favorable data from AVERROES and tempered by cautious optimism regarding apixaban’s outperforming warfarin in ARISTOTLE, apixaban’s inThought approvability index score in SPAF increases to 58%(C). For an overview of competitors in this therapeutic area, see inThought Research entitled Stroke Prevention in Atrial Fibrillation, published March 24, 2010.
