FDA Accepts Amgen's Supplemental Biologics License Application To Expand Indication For XGEVA® (denosumab) To Include Multiple Myeloma Patients
PRNewswire/ -- Amgen (NASDAQ: AMGN) today announced that the U.S. Food and Drug Administration (FDA) has accepted the XGEVA® (denosumab) supplemental Biologics License Application (sBLA) that seeks to expand the currently approved indication for the prevention of fractures and other skeletal-related events in patients with bone metastases from solid tumors to include patients with multiple myeloma. The FDA has set a Prescription Drug User Fee Act (PDUFA) action date of Feb. 3, 2018."Multiple myeloma patients with fractures and other bone complications have a very poor prognosis. Bisphosphonates are the only approved class of agents for the prevention of skeletal-related events in this patient population. However, these agents have several limitations, including kidney toxicity and acute phase reactions," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "Based on the data we have submitted to the FDA, we look forward to potentially making XGEVA available as a novel option for patients with multiple myeloma."XGEVA is the first fully human monoclonal antibody that binds to and neutralizes RANK ligand (RANKL) – a protein essential for the formation, function and survival of osteoclasts, which break down bone – thereby inhibiting osteoclast-mediated bone destruction. XGEVA is not cleared by the kidneys. XGEVA is indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors and is the number one prescribed agent by oncologists for this indication in the U.S. In the U.S., XGEVA currently has a limitation of use noting that it is not indicated for the prevention of skeletal-related events in patients with multiple myeloma.The sBLA, submitted on April 3, 2017, is based on the efficacy and safety data from the pivotal Phase 3 '482 study, the largest international multiple myeloma trial ever conducted, which successfully demonstrated that XGEVA is non-inferior to zoledronic acid in delaying the time to first on-study skeletal-related event in patients with multiple myeloma. The secondary endpoints of superiority in delaying time to first on-study skeletal-related event and delaying time to first-and-subsequent skeletal-related event were not met in this study. Progression-free survival was an exploratory endpoint. The hazard ratio of XGEVA versus zoledronic acid for progression-free survival was 0.82 (95 percent CI: 0.68, 0.99; descriptive p=0.036) and the median difference in progression-free survival between arms was 10.7 months in favor of XGEVA. Data from the '482 study are also the basis of an application for a variation to the marketing authorization submitted to the European Medicines Agency (EMA).
Datascope Corp/MAQUET Issues Worldwide Voluntary Recall of the System CS100, CS100i and CS300 Intra-Aortic Balloon Pumps for Potential Electrical Test Failure Code
Datascope Corp. is voluntarily performing a worldwide field correction of certain Intra-Aortic Balloon Pumps (IABPs) sold by Datascope Corp. for a potential electrical test failure code. AFFECTED PRODUCT PART NUMBER CS100i IABP 0998-UC-0446HXX; 0998-UC-0479HXX CS100 IABP 0998-00-3013-XX; 0998-UC-3013-XX CS300 IABP 0998-00-3023-XX; 0998-UC-3023-XX This field correction also applies to any System 98 or System 98XT IABP that was converted to a CS100i or CS300 IABP. Overall Action for User Patients receiving IABP therapy are in critical condition and sudden interruption of therapy could result in unsafe, hemodynamic instability. Maquet/Getinge indicates that the risk-benefit of using an affected CS100i, CS100 or CS300 IABP should be assessed by the medical team for each patient when no alternative IABP or alternative therapy is available. Please adhere to the following instructions when using affected devices:Pursuant to the USER Instruction WARNINGS, clinicians are instructed not to leave the patient unattended during IABP therapy. An additional hazard associated with a sudden shutdown is related to the static condition (no inflating or deflating) of the balloon during the interruption of therapy. It is important to note the following WARNING in the CS100i, CS100 or CS300 IABP Operating Instructions Manual:WARNING: The patient balloon should not remain inactive in the patient (i.e., not inflating or deflating) for more than 30 minutes due to the potential for thrombus formation. Until the service is performed, we recommend powering on the IABP prior to inserting the IAB catheter to allow the IABP to successfully complete its self-test. This action will take less than 60 seconds to perform. In the event the IABP fails to successfully complete the self-test and exhibits electrical test failure code 58, please remove the IABP from service and contact your local Maquet/Getinge Sales & Service Office. Datascope has received a complaint that has been associated with a patient death due to the failure of the device to initiate therapy. This complaint involved a CS300 IABP that did not pump due to an electrical test failure code #58 (power up vent tests fail), maintenance code #3, and an autofill failure. An electrical test failure code #58 is caused by a solenoid valve requiring more power than the solenoid driver board can deliver to open the valve. There are approximately 12,000 affected units sold globally. The affected IABP units were distributed in the U.S. and worldwide (in over 100 countries). Affected units were distributed between March 23, 2003, and December 11, 2013. Units distributed after December 11, 2013, are not affected by the field correction.A service representative from Datascope will be replacing the defective solenoid driver boards. Customers having affected IABP unit(s) will be contacted by a representative of the Maquet/Getinge Service Team to schedule on-site service.For additional information regarding this field correction, please contact the Customer Service Department at 1-888-627-8383 and Press 2 (Monday through Friday from 8:00 a.m. to 6:00 p.m. EDT).Adverse reactions or quality problems experienced with the use of this product may be reported to the FDA's MedWatch Adverse Event Reporting program either online, by regular mail or by fax.
John Paulson Joins Valeant Board Of Directors
LAVAL, Quebec, June 19, 2017 /PRNewswire/ -- Valeant Pharmaceuticals International, Inc. (NYSE: VRX and TSX: VRX) ("Valeant") today announced that its board of directors has elected John Paulson to serve as a director, effective June 14, 2017. With the addition of Mr. Paulson, Valeant has a total of 11 members on its board, 10 of whom are independent. "We are pleased to welcome John to Valeant's board of directors," said Joseph C. Papa, chairman and CEO, Valeant. "With his significant business and financial expertise, John will be a strong addition to the board. His experience will be especially valuable as we continue to execute on our transformational strategy to turnaround Valeant." Mr. Paulson is the president of Paulson & Co., Inc., a New York-based investment firm. "The strategic plan to transform Valeant smartly focuses on rebuilding the company's core franchises in ophthalmology, dermatology and gastroenterology while simultaneously using the proceeds from the sale of non-core assets and operating cash flow to de-lever the company," said Mr. Paulson. "I am fully supportive of the strategy and leadership team at Valeant."
Kalamazoo, Michigan - June 19, 2017- Stryker Corporation (NYSE:SYK) announced today a definitive agreement to acquire NOVADAQ Technologies Inc. (NASDAQ:NVDQ; TSX:NDQ) for US.75 per share, or US1 million with a net purchase price of US4 million, reflecting net cash of approximately US million. NOVADAQ is a leading developer of fluorescence imaging technology that provides surgeons with visualization of blood flow in vessels, and related tissue perfusion in cardiac, cardiovascular, gastrointestinal, plastic, microsurgical, and reconstructive procedures. NOVADAQ was founded in 2000 and is headquartered in Mississauga, Canada."This acquisition aligns with Stryker's focus on enabling our customers to see and do more by enhancing cross-specialty surgical visualization," stated Timothy J. Scannell, Group President, MedSurg and NeuroTechnology. "NOVADAQ'S unique innovative technology complements Stryker's advanced imaging portfolio and expands our product offerings into open and plastic reconstructive surgery. NOVADAQ'S innovative technology can reduce post-procedure complication rates and the cost of care for a broad variety of surgical treatments.""This transformative transaction recognizes the exceptional value we have built at NOVADAQ. Moreover, we believe it creates a strong opportunity for NOVADAQ, its customers, partners, shareholders, and employees," said Rick Mangat, President and Chief Executive Officer of NOVADAQ. "I am proud of the impact our SPY and PINPOINT technology has made throughout the world in breast reconstruction and colorectal surgery, as well as other minimally invasive applications, and look forward to the additional progress we can make as part of Stryker's organization."The transaction is structured as an arrangement under the Canada Business Corporations Act, subject to customary closing conditions, including approval by NOVADAQ'S shareholders and the Ontario Superior Court of Justice, the expiration or termination of the Hart-Scott-Rodino Antitrust Improvements Act waiting period and clearance under the Competition Act (Canada). The transaction is expected to close at the end of the third quarter and is expected to be dilutive to Stryker's 2017 adjusted net earnings per diluted share by !slideshow_deploy!.03 - !slideshow_deploy!.05. There is no change to Stryker's 2017 estimated adjusted net earnings per diluted share, which is in the range of .35 - .45. For 2018, this transaction is expected to be neutral to Stryker's earnings and accretive thereafter.Covington & Burling LLP and Osler, Hoskin & Harcourt LLP are serving as outside legal counsel for Stryker in connection with this transaction.Forward-looking statementsThis press release contains information that includes or is based on forward-looking statements within the meaning of the federal securities law that are subject to various risks and uncertainties that could cause our actual results to differ materially from those expressed or implied in such statements. Such factors include, but are not limited to: weakening of economic conditions that could adversely affect the level of demand for our products; pricing pressures generally, including cost-containment measures that could adversely affect the price of or demand for our products; changes in foreign exchange markets; legislative and regulatory actions; unanticipated issues arising in connection with clinical studies and otherwise that affect U.S. Food and Drug Administration approval of new products; potential supply disruptions; changes in reimbursement levels from third-party payors; a significant increase in product liability claims; the ultimate total cost with respect to the Rejuvenate and ABG II matter; the impact of investigative and legal proceedings and compliance risks; resolution of tax audits; the impact of the federal legislation to reform the United States healthcare system; changes in financial markets; changes in the competitive environment; our ability to integrate acquisitions, including the acquisition of NOVADAQ; and our ability to realize anticipated cost savings. Additional information concerning these and other factors is contained in our filings with the U.S. Securities and Exchange Commission, including our Annual Report on Form 10-K and Quarterly Reports on Form 10-Q.Stryker is one of the world's leading medical technology companies and, together with our customers, we are driven to make healthcare better. The Company offers a diverse array of innovative products and services in Orthopaedics, Medical and Surgical, and Neurotechnology and Spine that help improve patient and hospital outcomes. Stryker is active in over 100 countries around the world. Please contact us for more information at www.stryker.com.ContactsFor investor inquiries please contact: Katherine A. Owen, Stryker Corporation, 269-385-2600 or firstname.lastname@example.orgFor media inquiries please contact: Yin Becker, Stryker Corporation, 269-385-2600 or email@example.com
Update to Voluntary Recall of Eliquis® (apixaban) 5 mg Tablets (#HN0063) - Recall to retail/dispensing level only
On June 10, Bristol-Myers Squibb announced a voluntary recall of one lot (#HN0063) of Eliquisdisclaimer icon 5 mg tablets. This lot was distributed nationwide in the U.S. to wholesalers and retail pharmacies in February 2017. Bristol-Myers Squibb is taking this precautionary measure based on a single customer complaint that a bottle labeled as Eliquis5 mg was found to contain Eliquis 2.5 mg tablets. No other lots are impacted by this recall. This recall is to the retail/dispensing level and not to the consumer level. This recall is under way and is currently being executed. The recall is being conducted with the knowledge of the U.S. Food and Drug Administration. Patients should not stop taking Eliquis without consulting with their physician.Please see Eliquis U.S. Full Prescribing Information, including Boxed WARNINGSdisclaimer icon.
Data From Broad Clinical Program Show Investigational Erenumab is Effective at Preventing Migraine in Patients Experiencing Four or More Migraine Days a Month THOUSAND OAKS, Calif., June 8, 2017 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced that it will present 19 scientific abstracts at the 59th Annual Scientific Meeting of the American Headache Society (AHS) held June 8-11 in Boston. These include a new analysis from a pivotal Phase 2 study highlighting the efficacy of erenumab in patients with 15 or more headache days a month (chronic migraine) and a recent history of acute migraine medication overuse. Additionally, Amgen will present detailed clinical results and patient-reported outcomes data from two Phase 3 studies of erenumab, STRIVE and ARISE, for the prevention of migraine in patients who experience between four and 14 headache days a month (episodic migraine)."Migraine is a disabling disease for many patients. It disrupts daily living and the ability to function and participate in activities with loved ones," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "The data from our clinical program demonstrate that erenumab has a sustained effect in significantly reducing the number of days people suffer from migraine each month. Based on the benefit-risk profile seen in clinical studies, erenumab is poised to become the first migraine-specific preventive option blocking the calcitonin gene-related peptide, or CGRP, receptor that could help get many patients back to doing the things they love."Excessive use of acute pain-relief medications is common among people who suffer from migraine as they desperately try to control the symptoms. Among the patients experiencing 15 or more headache days a month in the erenumab Phase 2 study (n=667), 41 percent met strict criteria for medication overuse. Compared to a 3.5-day reduction in placebo, both dosages of erenumab reduced mean monthly migraine days by 6.6 by the end of the study (both p<0.001 versus placebo). Furthermore, days requiring acute pain-relief medications were also significantly reduced in both dosage arms (2.1-day reduction for placebo, compared to 5.4 days for erenumab 70 mg and 4.9 for erenumab 140 mg; both p<0.001 versus placebo).Detailed results from the positive six-month STRIVE study of erenumab 70 mg and 140 mg, and the positive three-month ARISE study of erenumab 70 mg will also be presented at the meeting. These data include both primary and secondary endpoints, evaluating the reduction in monthly migraine days and the percentage of patients who responded to erenumab. Results from STRIVE have been submitted for peer-reviewed publication.The safety profile of erenumab was similar to placebo across all treatment arms in the Phase 2 and Phase 3 studies. The most common adverse events across the studies were upper respiratory tract infection, injection site pain, nausea and nasopharyngitis.Erenumab is a human monoclonal antibody specifically designed for the prevention of migraine. Erenumab specifically inhibits the CGRP receptor, believed to play a critical role in mediating the incapacitating pain of migraine. Across the four placebo-controlled Phase 2 and Phase 3 clinical studies, more than 2,600 patients have been exposed to erenumab.These data support the first submissions in the United States (U.S.) and European Union for a CGRP pathway inhibitor in migraine prevention. In addition, an ongoing extension trial is underway evaluating people with migraine for up to five years.Amgen and Novartis will co-commercialize erenumab in the U.S. Amgen has exclusive commercialization rights to the drug in Japan and Novartis has exclusive rights to commercialize in rest of world.Amgen-sponsored abstracts at the 2017 Annual Scientific Meeting of the AHS include:Clinical StudiesEarly Onset of Efficacy in a Phase 2 Clinical Trial of Erenumab in Patients with Chronic Migraine Poster #PS24, Saturday, June 10, 6:30 a.m. – 5 p.m. ET A Multicenter, Open-label, Pharmacokinetic Drug Interaction Study of Erenumab (AMG 334) and a Combined Oral Contraceptive in Healthy Female Subjects (Ph1b DDI OC) Poster #PS23, Saturday, June 10, 6:30 a.m. – 5 p.m. ET Chronic Migraine Treatment with Erenumab: Responder Rates Poster #PS33, Saturday, June 10, 6:30 a.m. – 5 p.m. ET Efficacy of Erenumab for the Treatment of Patients with Chronic Migraine in Presence of Medication Overuse Poster #PS32, Saturday, June 10, 6:30 a.m. – 5 p.m. ET Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Erenumab (AMG 334) in Migraine Prevention: Primary Results of the STRIVE Trial Platform Presentation #IOR04, Saturday, June 10, 8:30 – 8:40 a.m. ET A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Erenumab in Migraine Prevention: Primary Results of the ARISE Trial Poster #PS21, Saturday, June 10, 6:30 a.m. – 5 p.m. ET A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Erenumab (AMG 334) in Chronic Migraine Prevention Platform Presentation #IOR07, Saturday, June 10, 9 – 9:10 a.m. ET Patient Reported Outcomes in Chronic Migraine Patients Receiving Placebo or Erenumab (AMG 334) in a Phase 2 Randomized, Double-Blind Study Poster #PS34, Saturday, June 10, 6:30 a.m. – 5 p.m. ET Patient-Reported Outcomes from the STRIVE Trial: A Phase 3, Randomized, Double-Blind Study of Erenumab in Subjects with Episodic Migraine Poster #PS35 Saturday, June 10, 6:30 a.m. – 5 p.m. ET Patient-Reported Outcomes from the ARISE Trial: A Phase 3, Randomized, Double-Blind Study of Erenumab in Subjects with Episodic Migraine Poster #PS22, Saturday, June 10, 6:30 a.m. – 5 p.m. ET Global Health EconomicsThe Impact of Physical Functioning in Adults with Chronic and Episodic Migraine Poster #PF47, Friday, June 9, 6:30 a.m. – 5 p.m. ET Patient Satisfaction with Current Prophylactic Migraine Medications Poster #PF02, Friday, June 9, 6:30 a.m. – 5 p.m. ET Risk of Cerebrovascular Events in Migraine Patients Treated with Prophylactic Medications Poster #PF66, Friday, June 9, 6:30 a.m. – 5 p.m. ET Development and Psychometric Validation of the Migraine Functional Impact Questionnaire (MFIQ): a New Instrument Measuring the Impact of Migraine on Physical, Social, and Emotional Functioning Poster #PF40, Friday, June 9, 6:30 a.m. – 5 p.m. ET How much change in headache-related disability is clinically meaningful? Estimating minimally important difference (MID) or change in MIDAS using data from the AMPP Study Poster #PF52, Friday, June 9, 6:30 a.m. – 5 p.m. ET Improving Communications Between People with Migraine and Healthcare Professionals for Optimized Migraine Management: A Modified Delphi Approach to Designing a Migraine Tracker App Poster #PS61, Saturday, June 10, 6:30 a.m. – 5 p.m. ET Healthcare Costs and Utilization and Medication Treatment Patterns Among Migraine Patients: A Retrospective Analysis Poster #PS58, Saturday, June 10, 6:30 a.m. – 5 p.m. ET Center for Observational ResearchRisk of Cardiovascular Events in Migraine Patients Treated with Prophylactic Medications Poster #PF03, Friday, June 9, 6:30 a.m. – 5 p.m. ET Late-Breaking ResearchEffect of Anti-CGRP Receptor Antibody AA58 on CGRP Receptor Internalization and Trafficking Late-Breaking Poster #PF85LB, Friday, June 9, 6:30 a.m. – 5 p.m. ET About the 20120295 Study The 20120295 study is a global Phase 2, randomized, 12-week, double-blind, placebo-controlled study evaluating the safety and efficacy of erenumab in chronic migraine prevention. In the study, 667 patients were randomized to receive once-monthly subcutaneous placebo or erenumab (70 mg or 140 mg) in a 3:2:2 ratio, respectively. The primary endpoint was change in monthly migraine days from baseline to the last four weeks of the 12-week treatment phase in patients with chronic migraine (the number of migraine days between weeks nine and 12). Secondary study endpoints included reduction of at least 50 percent from baseline in monthly migraine days, change from baseline in monthly acute migraine-specific medication days and change from baseline in cumulative monthly headache hours.About Erenumab Phase 3 Studies STRIVE (STudy to evaluate the efficacy and safety of erenumab in migRaIne preVEntion, 20120296) is a global Phase 3, multicenter, randomized six-month, double-blind, placebo-controlled study evaluating the safety and efficacy of erenumab in episodic migraine prevention. In the study, 955 patients were randomized to receive once-monthly subcutaneous placebo or erenumab (70 mg or 140 mg) in a 1:1:1 ratio. Patients enrolled in STRIVE were experiencing an average of 8.3 migraine days per month at baseline. The primary endpoint was change from baseline in mean monthly migraine days over the last three months of the double-blind treatment phase of the study (months 4, 5, 6). Secondary study endpoints included reduction of at least 50 percent from baseline in mean monthly migraine days, change from baseline in mean monthly acute migraine-specific medication days, and reductions from baseline in both mean impact on everyday activities domain and mean physical impairment domain scores on the Migraine Physical Function Impact Diary (MPFID).ARISE (A Phase 3, RandomIzed, double-blind, placebo-controlled Study to Evaluate the efficacy and safety of erenumab in migraine prevention, 20120297) is a global Phase 3, multicenter, randomized, three-month, double-blind, placebo-controlled study evaluating the safety and efficacy of erenumab in episodic migraine prevention. In the study, 577 patients were randomized to receive once-monthly subcutaneous placebo or erenumab (70 mg) in a 1:1 ratio. Study participants who completed the double-blinded portion had the option to continue in a long-term safety extension. Patients enrolled in ARISE were experiencing an average 8.3 migraine days each month at baseline. The primary endpoint was change from baseline in monthly migraine days from baseline to the last four weeks of the three-month treatment phase (the number of migraine days between weeks 9 and 12). Secondary study endpoints included reduction of at least 50 percent from baseline in monthly migraine days and change from baseline in monthly acute migraine-specific medication treatment days. The MPFID assessed two other secondary endpoints.About Erenumab Erenumab is a human monoclonal antibody specifically designed for the prevention of migraine. Erenumab specifically inhibits the receptor of the calcitonin gene-related peptide (CGRP) which is thought to play a causal role in migraine pathophysiology. Erenumab has been studied in several large global, randomized, double-blind, placebo-controlled trials to assess its safety and efficacy in migraine prevention.About Migraine Migraine is a distinct neurological disease.1 People with migraine lose a substantial portion of their lives to this illness, experiencing significant physical impairment, frequently accompanied by head pain, nausea, vomiting and meaningful disruption of daily activities.1 The World Health Organization ranks migraine as one of the most debilitating illnesses.2 For the approximately 10 million Americans whose migraine frequency or severity impacts daily activities, preventive medications may be an option.3 Approximately 3.5 million of these patients are currently on a preventive therapy, but up to 80 percent discontinue these within one year.3,4 Migraine is associated with personal and societal burdens of pain, disability, and financial cost, and it remains under-recognized and under-treated.About Amgen and Novartis Neuroscience Collaboration In August 2015, Amgen entered into a global collaboration with Novartis to jointly develop and commercialize pioneering treatments in the field of migraine and Alzheimer's disease (AD). The collaboration focuses on investigational Amgen drugs in the migraine field, including erenumab (Biologics License Application submitted to U.S. FDA in May 2017) and AMG 301 (currently in Phase 1 development). In April 2017, the collaboration was expanded to include co-commercialization of erenumab in the U.S. For the migraine program, Amgen retains exclusive rights in Japan, and Novartis has exclusive rights in Europe, Canada and rest of world. Also, the companies are partnering in the development and commercialization of a beta-secretase 1 (BACE) inhibitor program in AD. The oral therapy CNP520 (currently in Phase 3 for AD) is the lead molecule and further compounds from both companies' pre-clinical BACE inhibitor programs may be considered as follow-on molecules.About Amgen Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world's leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.For more information, visit www.amgen.com and follow us on www.twitter.com/amgen.Forward-Looking Statements This news release contains forward-looking statements that are based on the current expectations and beliefs of Amgen. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including estimates of revenues, operating margins, capital expenditures, cash, other financial metrics, expected legal, arbitration, political, regulatory or clinical results or practices, customer and prescriber patterns or practices, reimbursement activities and outcomes and other such estimates and results. Forward-looking statements involve significant risks and uncertainties, including those discussed below and more fully described in the Securities and Exchange Commission reports filed by Amgen, including our most recent annual report on Form 10-K and any subsequent periodic reports on Form 10-Q and Form 8-K. Unless otherwise noted, Amgen is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.No forward-looking statement can be guaranteed and actual results may differ materially from those we project. Our results may be affected by our ability to successfully market both new and existing products domestically and internationally, clinical and regulatory developments involving current and future products, sales growth of recently launched products, competition from other products including biosimilars, difficulties or delays in manufacturing our products and global economic conditions. In addition, sales of our products are affected by pricing pressure, political and public scrutiny and reimbursement policies imposed by third-party payers, including governments, private insurance plans and managed care providers and may be affected by regulatory, clinical and guideline developments and domestic and international trends toward managed care and healthcare cost containment. Furthermore, our research, testing, pricing, marketing and other operations are subject to extensive regulation by domestic and foreign government regulatory authorities. We or others could identify safety, side effects or manufacturing problems with our products after they are on the market. Our business may be impacted by government investigations, litigation and product liability claims. In addition, our business may be impacted by the adoption of new tax legislation or exposure to additional tax liabilities. If we fail to meet the compliance obligations in the corporate integrity agreement between us and the U.S. government, we could become subject to significant sanctions. Further, while we routinely obtain patents for our products and technology, the protection offered by our patents and patent applications may be challenged, invalidated or circumvented by our competitors, or we may fail to prevail in present and future intellectual property litigation. We perform a substantial amount of our commercial manufacturing activities at a few key facilities and also depend on third parties for a portion of our manufacturing activities, and limits on supply may constrain sales of certain of our current products and product candidate development. In addition, we compete with other companies with respect to many of our marketed products as well as for the discovery and development of new products. Discovery or identification of new product candidates cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate will be successful and become a commercial product. Further, some raw materials, medical devices and component parts for our products are supplied by sole third-party suppliers. Certain of our distributors, customers and payers have substantial purchasing leverage in their dealings with us. The discovery of significant problems with a product similar to one of our products that implicate an entire class of products could have a material adverse effect on sales of the affected products and on our business and results of operations. Our efforts to acquire other companies or products and to integrate the operations of companies we have acquired may not be successful. We may not be able to access the capital and credit markets on terms that are favorable to us, or at all. We are increasingly dependent on information technology systems, infrastructure and data security. Our stock price is volatile and may be affected by a number of events. Our business performance could affect or limit the ability of our Board of Directors to declare a dividend or our ability to pay a dividend or repurchase our common stock.The scientific information discussed in this news release related to our product candidates is preliminary and investigative. Such product candidates are not approved by the U.S. Food and Drug Administration, and no conclusions can or should be drawn regarding the safety or effectiveness of the product candidates.