Biotech Values

[DewDiligence]

Apixaban Bests Aspirin in AF/Stroke Prevention in Phase-3 AVERROES Study

[BMY/PFE reported the success and early termination of this phase-3 study, called AVERROES, in Jun 2010 (#msg-51162505, #msg-51176226), and they presented the detailed data at the European Society of Cardiology meeting on Aug 31. On the primary efficacy endpoint, the incidence of stroke or a systemic embolic event, Apixaban reduced the risk relative to aspirin by an astonishing 54%—i.e. a hazard ratio of 0.46; the 95% CI on this hazard ratio was [0.33,0.64], so the result was highly statsig. On the primary safety endpoint of major bleeding, Apixaban was not statsig worse than aspirin; the hazard ratio was 1.14 and the 95% CI was [0.74,1.75]. (These and other data are available on powerpoint slides at http://www.theheart.org/displayItem.do?primaryKey=1117067&type=ppt .)

Less thrombosis without more bleeding is the Holy Grail for anticoagulants, and the above results for Apixaban are outstanding. However, the AVERROES study addresses only the minority of AF patients (40-50%, according to BMY/PFE) who are unable to tolerate warfarin; that’s why some investors think BMY/PFE will hold off on submitting an NDA in AF/stroke prevention until seeing the results of the 18,000-patient phase-3 study called ARISTOTLE that compares Apixaban to warfarin in the same indication as the AVERROES study; according to clinicaltrials.gov (http://clinicaltrials.gov/ct2/show/study/NCT00412984 ), ARISTOTLE is expected to report data in Apr 2011.

See #msg-54545302 for the colossal size of the addressable market for new anticoagulants.]

http://www.nytimes.com/2010/09/01/business/01drug.html

›August 31, 2010
By NATASHA SINGER

For investors who have been asking themselves whether medium-size pharmaceutical companies can survive in an industry that has had recent mega-mergers, the answer seems to be yes. At least for Bristol-Myers Squibb.

The company’s experimental anticoagulant drug apixaban worked better than aspirin in preventing stroke and systemic blood clots for patients who have an irregular heart rhythm disorder called atrial fibrillation, according to new study data presented on Tuesday at a cardiology conference in Stockholm.

Investment bank analysts have estimated that a new generation of stroke prevention drugs like apixaban, if approved by the Food and Drug Administration, could generate $10 billion or more in annual global sales.

Patients taking apixaban had a rate of stroke or systemic blood clots of 1.6 percent a year, while those on aspirin had a rate of 3.6 percent a year, a statistically significant difference, according to a preliminary analysis of the new data. The rate of major bleeding was 1.2 percent a year for the apixaban group and 1.4 percent on aspirin — not a significant difference, researchers reported.

Atrial fibrillation affects about 2.2 million people in the United States, and that number is expected to double in the next 10 years, according to the National Heart, Lung and Blood Institute.

Bristol-Myers discovered apixaban and is developing the drug jointly with Pfizer. [The companies inked a joint-development deal in 2007 (#msg-19134406).] The study involved 5,600 patients who were unsuited for the standard treatment for atrial fibrillation, warfarin. [Apixaban is being compared to warfarin in a separate phase-3 study called ARISTOTLE—see below.]

In a note to investors on Tuesday, Christopher Schott, an analyst at J.P. Morgan, wrote that positive responses to the study data among leading cardiologists “suggest that apixaban will likely capture a disproportionate share,” by some estimates up to 50 percent, of patients who cannot tolerate warfarin.

The companies are also conducting a head-to-head trial of apixaban and warfarin in more than 18,000 patients with atrial fibrillation. The companies expect to report data from that study next year, a spokeswoman for Bristol-Myers Squibb said.

Indeed, apixaban is one of several drugs that pharmaceutical companies are developing in an effort to replace warfarin, a decades-old drug for atrial fibrillation. Prescription drugs like antibiotics, as well as foods rich in vitamin K, can affect the potency of warfarin. Also, patients on warfarin need regular blood tests to evaluate their clotting rate.‹