Bristol-Myers Squibb and Pfizer Present Observational Real-World Data Analysis on the Effectiveness and Safety of Eliquis® (apixaban) Compared to Warfarin in Select High-Risk Patients with Non-Valvular Atrial Fibrillation

In an analysis of four U.S. insurance databases, Eliquis was associated with a lower risk of stroke/systemic embolism (SE) and lower rates of major bleeding in select high-risk non-valvular atrial fibrillation (NVAF) patient subgroups

PRINCETON, NJ & NEW YORK, NY, USA I August 28, 2017 I Bristol-Myers Squibb Company (NYSE:BMY) and Pfizer Inc. (NYSE:PFE) today announced results from an analysis of real-world data pooled from four large U.S. insurance claims databases. Among non-valvular atrial fibrillation (NVAF) patients, Eliquis ^® (apixaban) was associated with a lower risk of stroke/SE and lower rates of major bleeding compared to warfarin for the overall population as well as for each of the selected high-risk patient sub-populations. The analysis will be presented today at ESC Congress 2017, organized by the European Society of Cardiology, in Barcelona, Spain.

In this real-world analysis, patients with NVAF receiving either Eliquis or other oral anticoagulants were identified through the U.S. Optum, MarketScan, PharMetrics, and Humana databases. The data was pooled after propensity score matching (PSM) was completed within each database. Select high-risk subgroups were stratified by age, CHA₂DS₂-VASc or HAS-BLED score, congestive heart failure (CHF), coronary artery disease (CAD), and peripheral artery disease (PAD). The CHA₂DS₂-VASc score is a method for estimating stroke risk in patients with non-valvular atrial fibrillation, and the HAS-BLED score helps to estimate risk of major bleeding in patients with NVAF. In the subgroup analysis, based upon these variables, Eliquis was associated with lower risk of stroke/SE and lower rates of major bleeding compared to warfarin after adjustment for confounding factors. It is important to note that Eliquis increases the risk of bleeding and can cause serious, potentially fatal, bleeding.

“Stroke events continue to be a major concern for patients with NVAF as well as their healthcare providers, and these findings supplement Eliquis clinical trial data,” said Christoph Koenen, M.D., MBA, VP, Development Lead, Eliquis, Bristol-Myers Squibb. “This real-world data analysis helps provide insight into how Eliquis fares in patient populations and settings that clinicians commonly see in practice.”

This observational cohort analysis adds to the body of evidence for Eliquis, which notably includes the Phase 3 ARISTOTLE (Apixaban for Reduction In STroke and Other ThromboemboLic Events in Atrial Fibrillation) clinical trial in which the reduction in risk for stroke/SE, the primary efficacy endpoint for ARISTOTLE, was generally consistent for Eliquis compared with warfarin across various patient subgroups.ⁱ Real-world data analyses cannot be used as stand-alone evidence to validate the efficacy and/or safety of a treatment. Observational real-world studies can only evaluate association and not causality^ii,iii (please see full methodology and additional limitations, as well as indications and important safety information for Eliquis, later in this press release).

“The global need to address stroke related to NVAF has never been greater, and the Bristol-Myers Squibb-Pfizer Alliance is intentionally focused on helping to reduce the risk of stroke for as many patients as possible among a broad range of patient type scenarios,” said Rory O’Connor, M.D., Chief Medical Officer, Pfizer Internal Medicine. “We believe real-world data analyses via the ACROPOLIS program are helping to advance deeper levels of insight into how different patient demographics, comorbidities and disease severity factor into how Eliquis may impact patient outcomes.”

In this analysis, Eliquis was associated with lower risk of stroke/SE and lower rates of major bleeding across these risk factors compared to warfarin (38,470 propensity score matched pairs), with a mean follow-up of six months.

Methodology
This observational, retrospective analysis was conducted in patients aged 18 years and older who initiated Eliquis or warfarin from January 1, 2013 to September 30, 2015. In each database, 1:1 PSM was used to balance age, gender, region, baseline comorbidities, and prescription comedications. Baseline characteristics were balanced with a mean age of 71 years, mean CHA₂DS₂-VASc score of 3.0 and mean HAS-BLED score of 2.6. After PSM within each database, the resulting patient-specific results were pooled. Cox proportional hazards models were used to estimate the hazard ratios of stroke/SE and major bleeding (identified using the first listed diagnosis of inpatient claims) within one year of therapy initiation for each subgroup. The statistical significance of the interaction between treatment and the specific subgroup(s) was evaluated.

Limitations of Real-World Data Analyses and of the Select High-Risk Patient Sub-Group Analysis
Real-world data have the potential to supplement randomized clinical trial data by providing additional information about how a medicine performs in routine medical practice. Real-world data analyses have several limitations. For example, the source and type of data used may limit the generalizability of the results and of the endpoints. Observational real-world studies can only evaluate association and not causality. Due to these limitations, real-world data analyses cannot be used as stand-alone evidence to validate the efficacy and/or safety of a treatment. It is important to note that, at this time, there are no head-to-head clinical trials comparing direct oral anticoagulants.

In this analysis, given the nature of claims data, diagnoses were identified through ICD-9-CM codes, and drug prescriptions were identified through prescription claims. Missing values, coding errors, and lack of clinical accuracy may have introduced bias into the study. Although some of the datasets contain information from different insurance plans that do not overlap at the plan level, others are employer-based claims datasets which may contain duplicate patient records when pooled together; however, the number of such duplicates is likely to be small – based on a published estimate of 0.5 percent^iv – and therefore unlikely to have any important effect on results.

About Eliquis

Eliquis (apixaban) is an oral selective Factor Xa inhibitor. By inhibiting Factor Xa, a key blood clotting protein, Eliquis decreases thrombin generation and blood clot formation. Eliquis is approved for multiple indications in the U.S. based on efficacy and safety data from multiple Phase 3 clinical trials. Eliquis is a prescription medicine indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (NVAF); for the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE), in patients who have undergone hip or knee replacement surgery; for the treatment of DVT and PE; and to reduce the risk of recurrent DVT and PE, following initial therapy.

About ACROPOLIS™
ACROPOLIS™ (Apixaban ExperienCe Through Real-WOrld POpuLatIon Studies) is the Eliquis (apixaban) global real-world data program designed to generate additional evidence from routine clinical practice settings to further inform healthcare decision makers, including healthcare providers and payers. The ACROPOLIS program will include retrospective, outcomes-based analyses from over 10 databases around the world, including medical records, medical and pharmacy health insurance claims data, and national health data systems.

Analyses of real-world data allow for a broader understanding of patient outcomes associated with Eliquis outside of the clinical trial setting, as well as insight into other measures of healthcare delivery, such as hospitalization and costs.

About ARISTOTLE
ARISTOTLE (Apixaban for Reduction In STroke and Other ThromboemboLic Events in Atrial Fibrillation) was designed to evaluate the efficacy and safety of Eliquis versus warfarin for the prevention of stroke or systemic embolism. In ARISTOTLE, 18,201 patients were randomized (9,120 patients to Eliquis and 9,081 to warfarin). ARISTOTLE was an active-controlled, randomized, double-blind, multi-national trial in patients with nonvalvular atrial fibrillation or atrial flutter, and at least one additional risk factor for stroke. Patients were randomized to treatment with Eliquis 5 mg orally twice daily (or 2.5 mg twice daily in selected patients, representing 4.7 percent of all patients) or warfarin (target INR range 2.0-3.0), and followed for a median of 1.8 years.

About the Bristol-Myers Squibb/Pfizer Collaboration
In 2007, Pfizer and Bristol-Myers Squibb entered into a worldwide collaboration to develop and commercialize apixaban, an oral anticoagulant discovered by Bristol-Myers Squibb. This global alliance combines Bristol-Myers Squibb’s long-standing strengths in cardiovascular drug development and commercialization with Pfizer’s global scale and expertise in this field.

About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol-Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube and Facebook.

About Pfizer Inc.: Working together for a healthier world ^®
At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products. Our global portfolio includes medicines and vaccines as well as many of the world’s best-known consumer health care products. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world’s premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 150 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.pfizer.com. In addition, to learn more, please visit us on www.pfizer.com and follow us on Twitter at @Pfizer and @PfizerNews, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer.

ⁱ Granger, CB,Alexander JH, McMurray JJV, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981-992.
ⁱⁱ Garrison LP, Neumann PJ, Erickson P, Marshall D, Mullins CD. Using real-world data for coverage and payment decisions: the ISPOR real-world data task force report. Value Health. 2007;10:326-335.
ⁱⁱⁱ Hannan EL. Randomized clinical trials and observational studies. J Am Coll Cardiol Intv. 2008;1:211-217.
^iv Broder MS, Neary MP, Chang E, et al. Treatments, complications, and healthcare utilization associated with acromegaly: a study in two large United States databases. Pituitary 2014; 17(4): 333–341.

SOURCE: Bristol-Myers Squibb