On August 24, 2016 Cantargia AB ("Cantargia") reported its interim report for January – June 2016 is available on the company website (www.cantargia.com/Investors/Reports) (Press release, Cantargia, AUG 24, 2016, View Source [SID:1234514711]).

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Significant events in the second quarter

· The exercise period for warrants of series TO 1 and TO 3 began on 23 March 2016 and ended on 13 April 2016. In total, 4,127,260 warrants of both series were exercised, representing around 83.5 per cent of the number of warrants issued. Through the warrants Cantargia raised approximately SEK 31.4 million before issue costs.

· During the period the Company gave investor presentations at the international BioEquity conference in Copenhagen on 10 May 2016 and at the Småbolagsdagen small cap investor event at the Sheraton Stockholm Hotel on 13 June 2016.

· The annual report for the financial year 2015 was published on 29 April 2016. The company held its Annual General Meeting on 25 May 2016 and published a report on the AGM the following day. The annual report and AGM report are available for download on the company’s website, www.cantargia.com.

· Cantargia received a Notice of Allowance from the US Patent Office for IL1RAP as target molecule for antibody-based treatment in acute lymphoblastic leukemia followed by a Notice of Allowance for IL1RAP as target molecule for antibody-based treatment in solid tumours from the same patent office. The company also received formal approval in Japan of a patent for solid tumours.

· The company announced that its CAN04 product candidate has been shown to have a high level safety in high doses – repeated treatment with up to 100 mg/kg. During the period Cantargia also decided that the company will conduct further process development studies to establish a strong foundation for long-term production and that the start of the GLP toxicity study will therefore be postponed until autumn 2016. Consequently, the start of clinical studies will also be postponed until the end of the first quarter of 2017.

· A third party filed an opposition to Cantargia’s patent in Europe for IL1RAP as a target molecule for antibody treatment and leukemia diagnostics. Cantargia will be working with its patent agents and the European Patent Office to conduct the process in a professional and correct manner.

Significant events after the end of the period

· In July Cantargia announced that the US Patent Office had approved the company’s application for IL1RAP as target molecule for antibody-based treatment of solid tumours.

· In August Cantargia announced that the company’s former CEO, Agneta Svedberg, has exercised 1,250 warrants of series 2011/2016. The exercise of the warrants will raise SEK 250,212.50 for Cantargia.

Financial information

First half (1 Jan 2016 – 30 Jun 2016)

· Other operating revenue was kSEK 0 (0).

· Earnings after financial items were kSEK -16,023 (-9,059).

· Earnings per share were approximately SEK -0.91 (-0.68).

· The equity/assets ratio was around 87 (89) per cent compared with the beginning of the year.

Second quarter (1 Apr 2016 – 30 Jun 2016)

· Other operating revenue was kSEK 0 (0).

· Earnings after financial items were kSEK -7,926 (-5,432).

· Earnings per share were approximately SEK -0.45 (-0.41).

Definitions

· Earnings per share: Profit for the period divided by 17,633,134 shares as at 30 June 2016.

· Equity/assets ratio: Equity divided by total capital.

· Unless otherwise indicated, figures in parentheses refer the same period in the previous year.

This constitutes information that Cantargia is required to publish under the EU’s Market Abuse Regulation. The information was submitted for publication through the above contact person at 8:30 (CEST) on August 24, 2016.

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On August 24, 2016 Agendia, Inc., a world leader in personalized medicine and molecular cancer diagnostics, reported the peer-reviewed publication of the primary outcome results of the Microarray In Node-negative and 1 to 3 positive lymph node Disease may Avoid ChemoTherapy (MINDACT) clinical trial in the prestigious New England Journal of Medicine (NEJM) (Press release, Agendia, AUG 24, 2016, View Source [SID:1234514712]). [i, iii, iv] The publication demonstrates that 46% of breast cancer patients considered for chemotherapy, whose tumors are classified MammaPrint Low Risk, have excellent survival without chemotherapy, and can thus be candidates to avoid this toxic therapy. [i, pg. 717]

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MINDACT is a collaboration between Agendia, the European Organization for Research and Treatment of Cancer (EORTC) and the Breast International Group (BIG). A unique phase III prospective, randomized, controlled study of 6,693 patients across 112 European cancer centers, MINDACT provides the highest level of clinical evidence (Level 1A) and confirms the clinical utility of using Agendia’s MammaPrint 70-gene breast cancer recurrence assay to help predict clinical outcome in women with early-stage breast cancer.

"When we developed MammaPrint, we knew we wanted to achieve the same level of evidence required for a typical pharmaceutical drug. That is why we are one of only a few diagnostic tests with FDA clearance and why we rigorously evaluated MammaPrint in the context of clinical-pathological factors in the randomized MINDACT trial," said Prof. Laura van ’t Veer, Chief Research Officer at Agendia, and Leader, Breast Oncology Program, and Director, Applied Genomics at UCSF Helen Diller Family Comprehensive Cancer Center. "Now indeed, we have the only genomic assay with Level 1A evidence to help physicians more accurately predict risk of distant metastasis in patients with early-stage breast cancer."

MINDACT is the first prospective translational clinical study of this magnitude in early-stage breast cancer to report the results of its primary objective and publish them in a peer-reviewed journal. At 5 years, patients who did not receive adjuvant chemotherapy but were classified as being at high risk for breast cancer recurrence based on clinical-pathological factors and as being at Low Risk based on MammaPrint, had similar rates of disease free survival. [i, pg. 717]

"The design of the MINDACT trial proves the clinical utility of the MammaPrint assay," said Dr. Gabriel Hortobagyi, MD, FACP, FASCO Professor and Chair Emeritus of the Department of Breast Medical Oncology at the MD Anderson Cancer Center (MDACC) and Chair of the Agendia Inc. Medical Advisory Board. "The reporting of these conclusive results of the trial will now give physicians increased confidence that in using MammaPrint, their treatment decisions will be based on the highest level of clinical evidence and will minimize the incidence of over- or under-treatment."

"We understand that a risk–benefit assessment and decisions with respect to the use of adjuvant chemotherapy are highly variable and personalized among physicians and individual patients. However, these findings provide clinical utility by demonstrating that MammaPrint’s accuracy in helping to detect patients with a low risk of distant recurrence could be safely used in the management of over one hundred thousand[ii] women and potentially spare them from unnecessary chemotherapy," said Dr. William Audeh, Chief Medical Officer at Agendia. "The toxicities and side effects of chemotherapy may outweigh the potentially small and non-statistically significant benefit (1.5% 95% CI, 0.50 to 1.21; p = 0.27) of chemotherapy in women at high risk based on clinical factors but at Low Risk per MammaPrint. Thus, physicians and breast cancer patients may on an individual basis decide to avoid it."

In MINDACT, when the authors looked at the patients with the most common type of breast cancer, hormone receptor positive, human epidermal growth factor receptor 2 negative, and lymph node negative (HR+/HER2-/LN0) disease, 75% were identified as having a Low Risk of recurrence using MammaPrint. The Distant Metastasis Free Interval (DMFI) for these patients (which according to the researchers is the optimal endpoint to evaluate a genomic assay that looks at prognosis and benefit of chemotherapy treatment) was 97.8% without chemotherapy. [i, supplement pg. 12-13]

In MINDACT, this MammaPrint Low Risk group of breast cancer patients who may be candidates to forgo chemotherapy is over four times larger than the proportion identified with a low-Recurrence Score (RS) in both TAILORx.[v] and Plan B.[vi]. The TAILORx trial, which is the trial that would validate the appropriate cut-offs for the Oncotype DX 21-gene breast cancer recurrence assay, has only reported data on the low risk arm of the study that included 15% of the patients who are in the non-randomized arm of patients with RS 10 and under. The TAILORx trial, has not presented results of its primary objective of the outcome of patients with RS between 11-25.

"MINDACT provides us with the highest level of evidence to support what we at Agendia have always believed, that MammaPrint is a definitive, accurate and clinically relevant breast cancer recurrence assay. The quality of life and cost efficiency implications of helping physicians choose the appropriate management for women with breast cancer is the reason we do what we do every day," commented Mark Straley, Chief Executive Officer, Agendia. "We understand that ultimately, the decision to receive or forgo chemotherapy lies with each patient and physician who is properly informed about the potential side effects and benefits of such treatment. Nonetheless, MammaPrint could potentially change the standard of care and we look forward to its recommendation for inclusion in all early-stage breast cancer management guidelines. This will ensure that even more patients, physicians and healthcare systems are aware of the benefits of MammaPrint-based management decisions."

Breast cancer is the most frequently diagnosed cancer in women worldwide.[vii] In 2012, there were nearly 1.7 million new breast cancer cases among women worldwide, accounting for 25% of all new cancer cases in women.[viii] MINDACT initial results were selected for a prestigious breakthrough presentation at the AACR (Free AACR Whitepaper) Annual Meeting 2016, 16-20 April.

For more information on the MINDACT trial publication, please visit the Agendia newsroom: View Source

[i] Cardosa F, van’t Veer LJ, Bogaerts J et al. 70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer. N Engl J Med 2016; 375: 717-29.
[ii] Based on applying MINDACT risk data to: American Cancer Society. Global Cancer Facts & Figures 3rd Edition. Atlanta: American Cancer Society; 2015. (online) and American Cancer Society. Breast Cancer Facts & Figures 2015-2016. Atlanta: American Cancer Society, Inc. 2015.
[iii] Hudis CA, Dickler, M. Increasing Precision in Adjuvant Therapy for Breast Cancer. N Engl J Med 2016; 375: 790-91.
[iv] For disclosures regarding involvement in trial, see page 728 of publication (Cardosa F. NEJM 2016) mentioned above.
[v] Sparano JA, Gray RJ, Makower DF, et al. Prospective validation of a 21-gene expression assay in breast cancer. N Engl J Med 2015; 373: 2005-14.
[vi] Gluz O, Nitz, U. A., Matthias, C, et al. West German Study Group Phase III Plan B Trial: First Prospective Outcome Data for the 21-Gene Recurrence Score Assay and Concordance of Prognostic Markers by Central and Local Pathology Assessment. J Clin Oncol 2016; 34(20):2341-9
[vii] World Health Organization. Breast cancer: prevention and control. Website. View Source Accessed March 2016.
[viii] American Cancer Society. Global Cancer Facts & Figures 3rd Edition. Atlanta: American Cancer Society; 2015. (online)

About MINDACT
MINDACT is a prospective, randomized, phase III, controlled clinical trial that investigates the clinical utility of MammaPrint, when used in conjunction with standard clinical pathological criteria, for the selection of patients unlikely to benefit from adjuvant chemotherapy. From 2007 to 2011, 6,693 women who had undergone surgery for early-stage breast cancer enrolled in the trial, across 112 centers in nine countries. Patients were categorized as low or high risk for tumor recurrence in two ways: first, through analysis of tumor tissue using MammaPrint; and second, using Adjuvant! Online, a tool that calculates risk of breast cancer recurrence based on common clinical pathological factors. Patients characterized in both clinical and genomic assessments as low risk are spared chemotherapy, while patients characterized as high risk are advised chemotherapy. Those with discordant results were randomized to use either clinical or genomic risk (MammaPrint) evaluation for chemotherapy treatment.
MINDACT is a population based trial. A risk–benefit assessment and decisions with respect to the use of chemotherapy are highly variable among physicians and patients, and even national and international guidelines differ in their recommendations. Ultimately, the decision to receive or forgo chemotherapy (or any other treatment) lies with each patient who is properly informed about the potential side effects and the potential benefits of such treatment. For the same risk–benefit scenario, different patients may make different decisions. [i, pg. 727-28]

About MammaPrint
MammaPrint is a FDA-cleared in vitro diagnostic test, performed in a single laboratory, using the gene expression profile of breast cancer tissue samples to assess a patients’ risk for distant metastasis. The MammaPrint result is indicated for use by physicians as a prognostic marker only, along with other clinical-pathological factors. MammaPrint is not intended for diagnosis, or to predict or detect response to therapy, or to help select the optimal therapy for patients. Results should be taken in the context of other relevant clinical-pathological factors and standard practice of medicine.

On August 24, 2016 BeiGene, Ltd. (NASDAQ:BGNE), a clinical-stage biopharmaceutical company focused on developing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, reported the appointment of Amy C. Peterson, M.D. as Chief Medical Officer, Immuno-oncology (Press release, BeiGene, AUG 24, 2016, View Source;ut=1472118472&p=RssLanding&cat=news&id=2197224 [SID:1234514748]). Dr. Peterson will lead the global clinical development of BGB-A317, BeiGene’s PD-1 inhibitor; BGB-290, BeiGene’s PARP inhibitor; and the expanding pipeline of other immuno-oncology agents expected to enter clinical development. Dr. Eric Hedrick, currently serving as the Interim Chief Medical Officer, will continue to oversee global clinical hematology development including the program for BGB-3111, BeiGene’s BTK inhibitor, and will remain serving as an advisor as BeiGene continues to expand its global clinical development capabilities.

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"We are delighted to have Dr. Peterson join our team," said John V. Oyler, Founder, Chief Executive Officer, and Chairman of BeiGene. "BeiGene continues to expand its senior medical leadership in response to emerging global development opportunities, particularly in immuno-oncology. Amy’s broad experience in oncology drug development and her academic background in immuno-oncology research are well-suited to our expanding clinical development efforts. We very much look forward to her contribution in the continued growth and development of our existing and future pipeline and the company as a whole."

"BeiGene has a robust pipeline of clinical stage, internally discovered molecules against validated targets as well as an expanding roster of candidates in the preclinical pipeline," said Dr. Peterson. "I look forward to leveraging my past experiences to successfully build an organization that can bring these assets to market while continuing to expand the clinical pipeline."

Prior to joining BeiGene, Dr. Peterson was Vice President of Clinical Development at Medivation, where she was primarily responsible for the development of enzalutamide and talazoparib in breast cancer and of pidilizumab in diffuse large b-cell lymphoma. Previously, she served as Associate Group Medical Director at Genentech, where she was responsible for the development of early stage molecules targeting multiple major pathways in oncology. Prior to joining Genentech, Dr. Peterson was an Instructor of Medicine in Oncology at the University of Chicago, where she conducted translational research in tumor immunology in conjunction with Dr. Thomas F. Gajewski.

Dr. Peterson received her M.D. from Thomas Jefferson University in Philadelphia, PA, and she completed her residency in Internal Medicine at Northwestern Memorial Hospital and Fellowship in Hematology and Oncology at the University of Chicago. She holds a Bachelor of Arts degree from Wesleyan University in Middletown, CT.

On August 23, 2016 Bristol-Myers Squibb Company (link is external) (NYSE: BMY) and Pfizer Inc.(NYSE: PFE) reported that 19 abstracts (late-breaking, rapid-fire, oral and poster presentations) will be presented at ESC Congress 2016, to be held August 27–31 in Rome, Italy (Press release, Pfizer, AUG 23, 2016, View Source [SID:1234514680]). These new data from post-hoc analyses from ARISTOTLE (Apixaban for Reduction In STroke and Other ThromboemboLic Events in Atrial Fibrillation) and retrospective real-world data analyses continue to underscore the Alliance’s commitment to the evaluation of Eliquisfor patients with nonvalvular atrial fibrillation (NVAF) and venous thromboembolism (VTE). Of note, several of the real-world data analyses are part of ACROPOLIS (Apixaban ExperienCe Through Real-WOrld POpuLatIon Studies), a global real-world data research program designed to further evaluate the effectiveness and safety of apixaban in routine clinical practice.

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"The Bristol-Myers Squibb and Pfizer Alliance is pleased to share 19 abstracts, which include new real-world analyses, as well as new sub-analyses from the pivotal Phase 3 ARISTOTLE trial," said Rory O’Connor, M.D., Chief Medical Officer, Internal Medicine, Pfizer Innovative Health. "We look forward to the opportunity to contribute to the scientific discussion and continued research during ESC Congress 2016."

"As patient and provider needs continue to evolve, it’s essential that we deepen our understanding of how medicines are working in real-world situations," said Jack Lawrence, M.D., Vice President, Cardiovascular Specialty Development, Bristol-Myers Squibb. "This year at ESC Congress 2016, we’ll be discussing new NVAF and VTE data that complement our robust body of clinical trial data."

The complete list of Bristol-Myers Squibb and Pfizer Alliance presentations is included below. Abstracts can be accessed on the ESC Congress 2016 website (link is external).

Title Presenting Author/Type Date/Time (BST) Location/Session
Phase 3 Clinical Trial Sub-Analyses
Patients with Atrial Fibrillation and History of Falls Are at High Risk for Bleeding but Have Less Bleeding with Apixaban than Warfarin: Results from the ARISTOTLE Trial
Session: New Trends in Antithrombotic Therapy for Atrial Fibrillation
Rao et al. /
Oral, Rapid Fire
Aug. 28,
11:10
Agora 1 – Poster Area
Efficacy and Safety of Apixaban versus Warfarin in Patients with Atrial Fibrillation and Active Cancer: Insights from the ARISTOTLE Trial
Session: New Trends in Antithrombotic Therapy for Atrial Fibrillation
Melloni et al. /
Oral, Rapid Fire
Aug. 28,
11:20
Agora 1 – Poster Area
Patients with Atrial Fibrillation Treated with Apixaban Are Less Likely to Discontinue Study Drug When Compared with Warfarin: Insights from the ARISTOTLE Trial
Session: Poster Session 3: Anticoagulation in Atrial Fibrillation III

Xavier et al. /
Poster
Aug. 28,
14:00
Poster Area
Real-World Data and Other Analyses
Contemporary Results from EHR Study of Real-World Bleeding Risk among Elderly and Overall Non-Valvular Atrial Fibrillation Patients Prescribed Apixaban, Dabigatran, Rivaroxaban and Warfarin
Session: New Trends in Antithrombotic Therapy for Atrial Fibrillation
Horblyuk et al. /
Oral, Rapid Fire
Aug. 28,
12:00
Agora 1 – Poster Area
Real-World Comparisons of Major Bleeding Risk and Major Bleeding-Related Hospitalization Costs among Elderly Non-Valvular Atrial Fibrillation Patients Newly Initiated on Apixaban or Warfarin
Session: Poster Session 3: Anticoagulation in Atrial Fibrillation

Lip et al. /
Poster
Aug. 28,
14:00
Poster Area
Is Major Bleeding Risk for Oral Anticoagulants Similar Between Non-Valvular Atrial Fibrillation Patients Newly Initiated on Warfarin and Propensity-Score Matched NOAC Initiators? A Real World Study
Session: Poster Session 3: Anticoagulation in Atrial Fibrillation
Lip et al. /
Poster
Aug. 28,
14:00
Poster Area
Major Bleeding Risk in Patients 75 Years of Age or Older with Non-Valvular Atrial Fibrillation Initiating Oral Anticoagulants: A ‘Real-World’ Comparison of Warfarin, Apixaban, Dabigatran, or Rivaroxaban
Session: Poster Session 3: Anticoagulation in Atrial Fibrillation II

Lip et al. /
Poster
Aug. 28,
14:00
Poster Area
Is There a Difference in Treatment Persistence Across Oral Anticoagulants? Results of a UK Cohort Study Evaluating Oral Anticoagulation Therapy in an Atrial Fibrillation Population
Session: Poster Session 3: Anticoagulation in Atrial Fibrillation
Stynes et al. /
Poster
Aug. 28,
14:00
Poster Area
Real-World Comparison of Major Bleeding and Associated Costs among Treatment-Naïve Non-Valvular Atrial Fibrillation Patients Initiating Apixaban or Warfarin
Session: Poster Session 3: Anticoagulation in Atrial Fibrillation II
Trocio et al. /
Poster
Aug. 28,
14:00
Poster Area
Aspirin, not without Bleeding Risk in the Real World: Results of a UK Cohort Study Evaluating the Use of Antiplatelet Therapy for Stroke Prevention in Atrial Fibrillation (AF)
Session: Poster Session 3: Anticoagulation in Atrial Fibrillation III
Ridha et al. / Poster
Aug. 28,
14:00
Poster Area
Is Aspirin Monotherapy Effective for Stroke Prevention in the Real World? A UK Cohort Study Evaluating the Incidence of Stroke in the Absence of Anticoagulation in Atrial Fibrillation (AF)
Session: Poster Session 3: Anticoagulation in Atrial Fibrillation II
Ridha et al. /
Poster
Aug. 28,
14:00
Poster Area
Differences in the Characteristics of Patients with Non-Valvular Atrial Fibrillation Who Are Newly Prescribed Apixaban, Rivaroxaban, Dabigatran and VKA in General Practice in the UK
Session: Poster Session 3: Anticoagulation in Atrial Fibrillation

Stynes et al. /
Poster
Aug. 28,
14:00
Poster Area
Risk of Bleeding with Non-Vitamin K Antagonists and Phenprocoumon in Routine Care Patients with Non-Valvular Atrial Fibrillation
Session: Poster Session 3: Anticoagulation in Atrial Fibrillation III

Hohnloser et al. /
Poster
Aug. 28,
14:00
Poster Area
Are Your Atrial Fibrillation (AF) Patients Protected from Ischaemic Stroke? Clinical Characteristics of AF Patients Eligible for Stroke Prevention but Remaining Untreated in UK Clinical Practice
Session: Poster Session 3: Anticoagulation in Atrial Fibrillation II

Ridha et al. /
Poster
Aug. 28,
14:00
Poster Area
Bleeding Risk for Non-Valvular AF Patients Prescribed Warfarin, or Standard Doses of Apixaban 5mg BID, Dabigatran 150mg BID or Rivaroxaban 20mg QD in Real-World Practice: Findings from EHR
Session: Are You Still Afraid about Bleeding Risk of Antithrombotic Therapy in Atrial Fibrillation?
Lip et al. /
Oral, Advances in Science
Aug. 28,
14:18
Minsk – Village 4
Demographic and Clinical Characteristics Associated with Initiation of Individual Oral Anticoagulants among Patients with Newly Diagnosed Venous Thromboembolism
Session: Poster Session 4: Thrombosis and Coagulation
Li et al. /
Poster
Aug. 29,
08:30
Poster Area
A Nationwide Register Study to Compare Bleeding Rates in Patients with Non-Valvular Atrial Fibrillation Prescribed Oral Anticoagulants
Session: Registries Atrial Fibrillation

Halvorsen et al. /
Late-Breaker
Aug. 29,
08:45
Raphael – The Hub
Costs of Major Adverse Outcomes in Patients with Incident Venous Thromboembolism in Clinical Practice in the United Kingdom
Session: Advances in Pulmonary Embolism

Cohen et al. /
Poster
Aug. 29,
16:03
Moderated Poster Station – Poster Area
Potential Impact of Apixaban on Hospital Resource Use in Patients with Venous Thromboembolism
Session: Antithrombotics in Daily Clinical Practice
Li et al. /
Oral, Rapid Fire
Aug 30,
17:24
Galileo – The Hub
About Eliquis

Eliquis (apixaban) is an oral selective Factor Xa inhibitor. By inhibiting Factor Xa, a key blood clotting protein, Eliquisdecreases thrombin generation and blood clot formation. Eliquis is approved for multiple indications in the U.S. based on efficacy and safety data from seven 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.

ELIQUIS Indications and Important Safety Information

Indications

ELIQUIS is indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation.

ELIQUIS is indicated 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.

ELIQUIS is indicated for the treatment of DVT and PE, and to reduce the risk of recurrent DVT and PE following initial therapy.

ELIQUIS Important Safety Information

WARNING: (A) PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK OF THROMBOTIC EVENTS, (B) SPINAL/EPIDURAL HEMATOMA

(A) Premature discontinuation of any oral anticoagulant, including ELIQUIS, increases the risk of thrombotic events. If anticoagulation with ELIQUIS is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant.

(B) Epidural or spinal hematomas may occur in patients treated with ELIQUIS who are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include:
use of indwelling epidural catheters
concomitant use of other drugs that affect hemostasis, such as nonsteroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants
a history of traumatic or repeated epidural or spinal punctures
a history of spinal deformity or spinal surgery
optimal timing between the administration of ELIQUIS and neuraxial procedures is not known

Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary.

Consider the benefits and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated.
CONTRAINDICATIONS

Active pathological bleeding
Severe hypersensitivity reaction to ELIQUIS (e.g., anaphylactic reactions)
WARNINGS AND PRECAUTIONS

Increased Risk of Thrombotic Events after Premature Discontinuation: Premature discontinuation of any oral anticoagulant, including ELIQUIS, in the absence of adequate alternative anticoagulation increases the risk of thrombotic events. An increased rate of stroke was observed during the transition from ELIQUIS to warfarin in clinical trials in atrial fibrillation patients. If ELIQUIS is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant.
Bleeding Risk: ELIQUIS increases the risk of bleeding and can cause serious, potentially fatal, bleeding.
Concomitant use of drugs affecting hemostasis increases the risk of bleeding, including aspirin and other antiplatelet agents, other anticoagulants, heparin, thrombolytic agents, SSRIs, SNRIs, and NSAIDs.
Advise patients of signs and symptoms of blood loss and to report them immediately or go to an emergency room. Discontinue ELIQUIS in patients with active pathological hemorrhage.
There is no established way to reverse the anticoagulant effect of apixaban, which can be expected to persist for at least 24 hours after the last dose (i.e., about two half-lives). A specific antidote for ELIQUIS is not available.
Spinal/Epidural Anesthesia or Puncture: Patients treated with ELIQUIS undergoing spinal/epidural anesthesia or puncture may develop an epidural or spinal hematoma which can result in long-term or permanent paralysis.
The risk of these events may be increased by the postoperative use of indwelling epidural catheters or the concomitant use of medicinal products affecting hemostasis. Indwelling epidural or intrathecal catheters should not be removed earlier than 24 hours after the last administration of ELIQUIS. The next dose of ELIQUIS should not be administered earlier than 5 hours after the removal of the catheter. The risk may also be increased by traumatic or repeated epidural or spinal puncture. If traumatic puncture occurs, delay the administration of ELIQUIS for 48 hours.

Monitor patients frequently and if neurological compromise is noted, urgent diagnosis and treatment is necessary. Physicians should consider the potential benefit versus the risk of neuraxial intervention in ELIQUIS patients.

Prosthetic Heart Valves: The safety and efficacy of ELIQUIS have not been studied in patients with prosthetic heart valves and is not recommended in these patients.
Acute PE in Hemodynamically Unstable Patients or Patients who Require Thrombolysis or Pulmonary Embolectomy: Initiation of ELIQUIS is not recommended as an alternative to unfractionated heparin for the initial treatment of patients with PE who present with hemodynamic instability or who may receive thrombolysis or pulmonary embolectomy.
ADVERSE REACTIONS

The most common and most serious adverse reactions reported with ELIQUIS were related to bleeding.
TEMPORARY INTERRUPTION FOR SURGERY AND OTHER INTERVENTIONS

ELIQUIS should be discontinued at least 48 hours prior to elective surgery or invasive procedures with a moderate or high risk of unacceptable or clinically significant bleeding. ELIQUIS should be discontinued at least 24 hours prior to elective surgery or invasive procedures with a low risk of bleeding or where the bleeding would be noncritical in location and easily controlled. Bridging anticoagulation during the 24 to 48 hours after stopping ELIQUIS and prior to the intervention is not generally required. ELIQUIS should be restarted after the surgical or other procedures as soon as adequate hemostasis has been established.
DRUG INTERACTIONS

Strong Dual Inhibitors of CYP3A4 and P-gp: Inhibitors of cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) increase exposure to apixaban and increase the risk of bleeding. For patients receiving ELIQUIS doses of 5 mg or 10 mg twice daily, reduce the dose of ELIQUIS by 50% when ELIQUIS is coadministered with drugs that are strong dual inhibitors of CYP3A4 and P-gp (e.g., ketoconazole, itraconazole, ritonavir, or clarithromycin). In patients already taking 2.5 mg twice daily, avoid coadministration of ELIQUIS with strong dual inhibitors of CYP3A4 and P-gp.
Strong Dual Inducers of CYP3A4 and P-gp: Avoid concomitant use of ELIQUIS with strong dual inducers of CYP3A4 and P-gp (e.g., rifampin, carbamazepine, phenytoin, St. John’s wort) because such drugs will decrease exposure to apixaban and increase the risk of stroke and other thromboembolic events.
Anticoagulants and Antiplatelet Agents: Coadministration of antiplatelet agents, fibrinolytics, heparin, aspirin, and chronic NSAID use increases the risk of bleeding. APPRAISE-2, a placebo-controlled clinical trial of apixaban in high-risk post-acute coronary syndrome patients treated with aspirin or the combination of aspirin and clopidogrel, was terminated early due to a higher rate of bleeding with apixaban compared to placebo.
PREGNANCY CATEGORY B

There are no adequate and well-controlled studies of ELIQUIS in pregnant women. Treatment is likely to increase the risk of hemorrhage during pregnancy and delivery. ELIQUIS should be used during pregnancy only if the potential benefit outweighs the potential risk to the mother and fetus.
Please see full Prescribing Information, including BOXED WARNINGS and Medication Guide, available atwww.bms.com (link is external).

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.

On August 23, 2016 Medtronic plc (NYSE: MDT), the global leader in medical technology, reported that it has completed its acquisition of HeartWare International, Inc., a leading innovator of less-invasive, miniaturized, mechanical circulatory support technologies (MCS) for treating patients with advanced heart failure (Press release, Medtronic, AUG 23, 2016, View Source;p=RssLanding&cat=news&id=2196837 [SID:1234514704]). HeartWare will become part of the Heart Failure business within the Medtronic Cardiac Rhythm and Heart Failure division. Under the terms of the transaction, each outstanding share of HeartWare common stock has been converted into the right to receive $58.00 in cash, without interest, subject to any required withholding of taxes.

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HeartWare develops and manufactures miniaturized implantable heart pumps, or ventricular assist devices (VAD), to treat patients around the world suffering from advanced heart failure. Its flagship product, the HVAD System, features the world’s smallest full-support VAD and is indicated for refractory end-stage left-ventricular heart failure patients in the U.S. who are awaiting a heart transplant, as well as approved in Europe for long-term use in patients at risk of death from refractory, end-stage heart failure.
Medtronic estimates that the global VAD market is approximately $800 million currently, and worldwide is expected to grow in the mid-to-high single digits for calendar years 2016-17, and accelerate to high-single/low-double digits beyond calendar year 2017.
"Not only does the current HeartWare portfolio expand Medtronic leadership across the heart failure continuum, its product pipeline – when married with our expertise – can result in progressively less-invasive heart pumps that have the potential to benefit even more patients," said David Steinhaus, M.D., vice president and general manager of the Heart Failure business, and medical director for the Cardiac Rhythm and Heart Failure division at Medtronic. "Today, Medtronic offers the industry’s leading cardiac resynchronization therapy devices, including MR-conditional CRT-defibrillators; MCS therapy for advanced heart failure patients; heart failure diagnostics; and meaningful expert analysis through Medtronic Care Management Services, including the recently launched Beacon Heart Failure Management Service."

The acquisition of HeartWare broadens the Medtronic portfolio of therapies, diagnostic tools and services for patients suffering from heart failure, aligning with Medtronic’s Mission of alleviating pain, restoring health and extending life. The acquisition is part of the Company’s therapy innovation strategy to surround the physician with innovative products while focusing on patients and disease states.

"This is an exciting moment, as more than 600 HeartWare employees are now part of the broader Medtronic organization," said Doug Godshall, who served as president and chief executive of HeartWare for the past decade. "HeartWare has delivered incredible advancements for patients suffering from heart failure, through the commercialization of the HVAD system and pipeline development, and I am convinced that being part of Medtronic will allow us to accelerate meaningful innovations even more quickly."

Heart failure, also known as congestive heart failure, is a condition in which the heart isn’t pumping enough blood to meet the body’s needs. Heart failure usually develops slowly after an injury to the heart. Some injuries may include a progressive deterioration of the heart muscle, heart attack, untreated high blood pressure, or heart valve disease. Heart failure remains a leading cause of hospitalization and death in the United States, and its prevalence continues to increase, affecting more than 5 million people in the U.S. alone. The cost of heart failure is high. Healthcare expenditures in the U.S. on heart failure are estimated to be approximately $39 billion per year, making it one of the largest expenses to the healthcare system. With the aging of the population, Medtronic estimates that the number of patients with heart failure could exceed 8 million by 2030.

This transaction is expected to meet Medtronic’s long-term financial metrics for acquisitions. Medtronic does not intend to modify its fiscal year 2017 revenue outlook or earnings per share (EPS) guidance as a result of this transaction, although it is expected to provide increased confidence in the company’s ability to deliver on its FY17 revenue growth outlook. In addition, Medtronic expects minimal to no net EPS dilution from this transaction for the first two years as the company intends to offset the expected dilutive impact. The acquisition is expected to be earnings accretive in year three.

In collaboration with leading clinicians, researchers and scientists worldwide, Medtronic offers the broadest range of innovative medical technology for the interventional and surgical treatment of cardiovascular disease and cardiac arrhythmias. The company strives to offer products and services of the highest quality that deliver clinical and economic value to healthcare consumers and providers around the world.

The Tender Offer and Merger
The tender offer for all of the outstanding shares of HeartWare common stock expired as scheduled immediately after 11:59 p.m. Eastern time on August 22, 2016. Computershare Trust Company, N.A., the depositary and paying agent for the tender offer, has advised Medtronic that 14,952,817 shares of HeartWare common stock were validly tendered and not properly withdrawn in the tender offer, representing approximately 85.15% of the outstanding shares. All of the conditions to the tender offer have been satisfied, and on August 23, 2016, Medtronic Acquisition Corp., a subsidiary of Medtronic, accepted for payment and will promptly pay for all shares validly tendered and not properly withdrawn in the tender offer.

Following acceptance of the tendered shares, Medtronic completed its acquisition of HeartWare through the merger of Medtronic Acquisition Corp. with and into HeartWare without a vote of HeartWare’s stockholders pursuant to Section 251(h) of the Delaware General Corporation Law. As a result of the merger, HeartWare became a wholly-owned subsidiary of Medtronic. In connection with the merger, all HeartWare shares not validly tendered into the tender offer (other than shares (i) owned by HeartWare as treasury stock or owned by Medtronic, Inc. or Medtronic Acquisition Corp., which shares were cancelled and retired and cease to exist or (ii) held by any person who was entitled to and has properly demanded statutory appraisal of his or her shares) have been cancelled and converted into the right to receive the same $58.00 per share in cash, without interest, subject to any required withholding of taxes, as will be paid for all shares that were validly tendered and not properly withdrawn in the tender offer. HeartWare common stock will cease to be traded on The NASDAQ Stock Market LLC.