Li Ka Shing Knowledge Institute

Toronto, Canada

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Toronto, Canada
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News Article | May 4, 2017
Site: www.eurekalert.org

TORONTO, May 4, 2017--A study published today suggests that a select group of patients with rectal cancer who undergo chemotherapy and radiation may have low rates of recurrence and good survival rates regardless of whether they go on to have surgery. The conventional treatment for people with cancer of the rectum - the final part of the large intestine, ending at the anus - that has spread to nearby tissues or lymph nodes but not to other organs is chemoradiation to shrink the tumour, followed by surgery. But the surgery can result in complications, a permanent colostomy and poor quality of life. Some patients have such a dramatic response to chemotherapy and radiation that there is no detectable tumour at the time of surgery, said Dr. Fahima Dossa, the study's lead author and a surgical resident at St. Michael's Hospital. These patients, termed complete responders, have excellent survival and low rates of cancer recurrence, which raises questions about whether they benefit from surgery, said Dr. Dossa. Since 2004, some surgeons have offered these patients the option of surgery or a "watch-and-wait" approach that involves close followup. However, the safety of that approach remains unclear. In a paper published online today in The Lancet Gastroenterology & Hepatology, Dr. Dossa and her team conducted a systematic review and meta-analysis of 23 studies involving 867 patients who adopted the "watch-and-wait" approach. Cancer returned in the rectum of only 15.7 per cent of these patients. "What is striking is not only the low rate of cancer recurrence, but also that almost all the patients who had a recurrence could still be treated with surgery or radiation at the time the recurrence was detected," said Dr. Dossa. Only three patients with a recurrence could not undergo further treatment -- either surgery or more radiation - due to the extent of the renewed cancer. The analysis did not find differences in mortality between those who took the watch-and-wait approach and those who underwent surgery. Dr. Nancy Baxter, the study's senior author and chief of general surgery at St. Michael's, said that while many of the studies were small, the evidence to support a "watch-and-wait" approach is growing, challenging the current standards of care for rectal cancer. "The fact that patients in these studies chose to avoid surgery despite not knowing the safety of this approach is a reminder of the various factors that go into cancer treatment decisions," said Dr. Baxter. "At the very least, we are hopeful that this study will open the door to discussions between select patients and their surgeons about the option of a watch-and-wait approach. St. Michael's Hospital provides compassionate care to all who enter its doors. The hospital also provides outstanding medical education to future health care professionals in more than 29 academic disciplines. Critical care and trauma, heart disease, neurosurgery, diabetes, cancer care, and care of the homeless are among the Hospital's recognized areas of expertise. Through the Keenan Research Centre and the Li Ka Shing International Healthcare Education Center, which make up the Li Ka Shing Knowledge Institute, research and education at St. Michael's Hospital are recognized and make an impact around the world. Founded in 1892, the hospital is fully affiliated with the University of Toronto. For more information or to arrange an interview, please contact:


Women who were exposed to colder temperatures during pregnancy had a lower rate of gestational diabetes than those exposed to hotter temperatures TORONTO, May 15, 2017 - Women who were exposed to colder temperatures during pregnancy had a lower rate of gestational diabetes than those exposed to hotter temperatures, according to a study published online today in the Canadian Medical Association Journal. The prevalence of gestational diabetes was 4.6 per cent among women exposed to extremely cold average temperatures (equal to or below -10 C) in the 30-day period prior to being screened for gestational diabetes, and increased to 7.7 per cent among those exposed to hot average temperatures (above 24 C). The study also found that for every 10-degree Celsius rise in temperature, women were six to nine per cent more likely to develop gestational diabetes. The study examined 555,911 births among 396,828 women over a 12-year period. All the women studied lived in the Greater Toronto Area, but some were pregnant when the average temperature was warmer, and some when it was cooler. Researchers looked at the relationship between the average 30-day air temperature prior to the time of gestational diabetes screening in the second trimester, and the likelihood of gestational diabetes diagnosis. Dr. Gillian Booth, a researcher at St. Michael's and the Institute for Clinical Evaluative Sciences (ICES) and lead author of the study, said the finding might seem counterintuitive, but can be explained by emerging science about how humans make different kinds of fat. "Many would think that in warmer temperatures, women are outside and more active, which would help limit the weight gain in pregnancy that predisposes a woman to gestational diabetes," said Dr. Booth. "However, it fits a pattern we expected from new studies showing that cold exposure can improve your sensitivity to insulin, by turning on a protective type of fat called brown adipose tissue." A similar effect was seen for each 10-degree Celsius rise in the temperature difference between two consecutive pregnancies compared within the same woman. "By further limiting our analysis to pregnancies within the same woman, we controlled for a whole number of factors," said Dr. Joel Ray, a researcher at St. Michael's and ICES who co-led the study. "Doing so allowed us to eliminate factors like ethnicity, income, activity and eating habits that would differ between two different women." In addition to a higher rate of gestational diabetes among women who were exposed to hotter temperatures during pregnancy, there was also a lower rate of gestational diabetes among Canadian women born in cooler climates versus those who were born in hot climates. Those women born in cooler climates, including Canada and the United States, and who were exposed to cold temperatures during the 30-day period prior to screening had a gestational diabetes rate of 3.6 per cent, while those exposed to hot temperatures had a rate of gestational diabetes of 6.3 per cent. In comparison, women who were born in hot climates, including South Asia, Africa and the Middle East, had rates of gestational diabetes of 7.7 and 11.8 per cent, respectively. According to Drs. Booth and Ray, the findings, combined with the continued rise in global temperatures, could signal an increase in the future number of gestational diabetes cases worldwide. "While changes in temperature of this magnitude may lead to a small relative increase in the risk of gestational diabetes, the absolute number of women impacted in Canada and elsewhere may be substantial," they wrote. Gestational diabetes is new onset diabetes in the second trimester of pregnancy and is usually temporary, but the risk factors for gestational diabetes and adult onset type 2 diabetes are virtually the same. The results of this study could foreshadow the effects of rising world-wide temperatures on type 2 diabetes in general, according to the researchers. "This is like the canary in the coal mine for the possible effects of global warming on adult onset diabetes," said Drs. Booth and Ray. This study was funded by the St. Michael's Hospital Foundation and the Canadian Institutes of Health Research (CIHR). St. Michael's Hospital provides compassionate care to all who enter its doors. The hospital also provides outstanding medical education to future health care professionals in 29 academic disciplines. Critical care and trauma, heart disease, neurosurgery, diabetes, cancer care, care of the homeless and global health are among the hospital's recognized areas of expertise. Through the Keenan Research Centre and the Li Ka Shing International Healthcare Education Centre, which make up the Li Ka Shing Knowledge Institute, research and education at St. Michael's Hospital are recognized and make an impact around the world. Founded in 1892, the hospital is fully affiliated with the University of Toronto. ICES is an independent, non-profit organization that uses population-based health information to produce knowledge on a broad range of health care issues. Our unbiased evidence provides measures of health system performance, a clearer understanding of the shifting health care needs of Ontarians, and a stimulus for discussion of practical solutions to optimize scarce resources. ICES knowledge is highly regarded in Canada and abroad, and is widely used by government, hospitals, planners, and practitioners to make decisions about care delivery and to develop policy. For the latest ICES news, follow us on Twitter: @ICESOntario For more information, or to arrange an interview with one of the authors, please contact: Deborah Creatura Media Advisor, ICES deborah.creatura@ices.on.ca (o) 416-480-4780 or (c) 647-406-5996


Sanofi and Regeneron Announce Positive Results from First Dedicated Studies Evaluating Praluent® (alirocumab) in Individuals with Diabetes and Hypercholesterolemia - Data presented at the 77th Scientific Sessions of the American Diabetes Association (ADA) - Paris, France and Tarrytown, N.Y., June 11, 2017 - Sanofi and Regeneron Pharmaceuticals, Inc. today announced positive results from two Phase 3b/4 ODYSSEY-DM trials in patients with diabetes. In the studies, Praluent® (alirocumab), when administered on top of maximally tolerated doses (MTD) of statins, significantly reduced low-density lipoprotein cholesterol (LDL-C), the primary endpoint of the ODYSSEY DM-INSULIN study, and was superior to usual care in reducing non-high-density lipoprotein cholesterol (non-HDL-C), the primary endpoint of the ODYSSEY DM-DYSLIPIDEMIA study. Both studies also found that a majority of patients reached their lipid goals with Praluent 75 mg every two weeks, with an overall safety profile comparable to the ODYSSEY Phase 3 program. The results were unveiled today as part of the official symposium of the 77th Scientific Sessions of the American Diabetes Association (ADA) in San Diego, CA, titled, "Inhibition of PCSK9 in Dyslipidemia Patients with Diabetes." The data were also featured in the official ADA Scientific Sessions Advance program. "Patients with long-standing diabetes, including insulin-treated patients, are at high risk of cardiovascular disease," said Lawrence Leiter, M.D., chair of the ODYSSEY DM Steering Committee and director of the Lipid Clinic at the Li Ka Shing Knowledge Institute at St. Michael's Hospital, University of Toronto, Canada. "The positive results from ODYSSEY DM-INSULIN provide valuable information on the efficacy and safety of Praluent in this high cardiovascular risk group." Most people with diabetes will develop atherosclerotic cardiovascular disease (ASCVD). Despite current standard of care, nearly 70 percent of people age 65 or older with diabetes die from some form of heart disease, and 16 percent die of stroke.1 "Mixed dyslipidemia is common in people with type 2 diabetes and further increases CV risk, and yet it is difficult to treat with available therapies," said Robert Henry, M.D., member of the ODYSSEY DM Steering Committee and Director of the Center for Metabolic Research at the VA San Diego Healthcare System. "The results of ODYSSEY DM-DYSLIPIDEMIA showed that in a real-world setting, Praluent, on top of maximally tolerated doses of statins, significantly reduced non-HDL-C, another measure of bad cholesterol, and was superior to usual care. Praluent may be another option for physicians who need to further help their diabetes patients with clinical ASCVD manage their lipid profiles." In ODYSSEY DM-INSULIN, patients were randomized to Praluent 75 mg every two weeks or placebo in addition to MTD statins. Praluent dose was adjusted at week 12 to 150 mg every two weeks if their LDL-C was greater than or equal to 70 mg/dL at week 8. Approximately 80 percent of patients reached their LDL-C goals with Praluent 75 mg every two weeks in this study. In ODYSSEY DM-DYSLIPIDEMIA, patients were randomized to Praluent 75 mg every two weeks or usual care in addition to MTD statins. Praluent dose was adjusted at week 12 to 150 mg every two weeks if their non-HDL-C was greater than or equal to 100 mg/dL at week 8. Approximately 64 percent of patients reached their lipid goals with the Praluent 75 mg dose. ODYSSEY DM-INSULIN was a randomized, double-blind, placebo-controlled, parallel-group multicenter study that evaluated Praluent in 517 people with type 1 and type 2 diabetes on insulin with high CV risk and hypercholesterolemia who took MTD statins.2 The primary endpoint was percent change in calculated LDL-C from baseline to week 24. Results in the type 2 diabetes study population (n=441) were presented at ADA and showed: ODYSSEY DM-DYSLIPIDEMIA was a randomized, open-label, parallel-group, multicenter, multinational study designed to evaluate the superiority of Praluent versus usual care in 413 people with type 2 diabetes and mixed dyslipidemia at high CV risk, not adequately controlled with MTD statins.3 The primary endpoint was percent change in non-HDL-C from baseline to week 24. Non-HDL-C is calculated as total cholesterol minus high-density lipoprotein cholesterol, and provides a single index of all the potentially atherogenic, apolipoprotein (apo) B-containing lipoproteins, including LDL, very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and lipoprotein(a). In the previously reported results from the ODYSSEY LONG TERM study in which all patients were treated with Praluent 150 mg on top of MTD statins, Praluent reduced LDL-C by 60 percent from baseline in patients with diabetes (n=545) at week 24.4 The recommended starting dose of Praluent is 75 mg administered subcutaneously every 2 weeks, or alternatively 300 mg every 4 weeks (monthly) for patients who prefer less frequent dosing. The majority of patients taking Praluent achieve sufficient LDL-C reduction with the 75 mg dose. If the LDL-C response is inadequate, the dosage may be adjusted to the maximum dosage of 150 mg administered every 2 weeks. About Praluent Praluent inhibits the binding of PCSK9 (proprotein convertase subtilisin/kexin type 9) to the LDL receptor and thereby increases the number of available LDL receptors on the surface of liver cells, which results in lower LDL-C levels in the blood. Praluent is approved in more than 50 countries worldwide, including the U.S., Japan, Canada, Switzerland, Mexico and Brazil, as well as the European Union (EU). In the U.S., Praluent is approved for use as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or clinical ASCVD who require additional lowering of LDL-C. In the EU, Praluent is approved for the treatment of adult patients with primary hypercholesterolemia (HeFH and non-familial) or mixed dyslipidemia as an adjunct to diet: a) in combination with a statin, or statin with other lipid-lowering therapies in patients unable to reach their LDL-C goals with the maximally-tolerated statin or b) alone or in combination with other lipid-lowering therapies for patients who are statin intolerant, or for whom a statin is contraindicated. The effect of Praluent on CV morbidity and mortality has not yet been determined. ODYSSEY OUTCOMES is prospectively evaluating the effect of Praluent on the occurrence of CV events in approximately 18,000 patients who have experienced an acute coronary syndrome. This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. Important Safety Information for the U.S. Do not use Praluent if you are allergic to alirocumab or to any of the ingredients in Praluent. Before you start using Praluent, tell your healthcare provider about all your medical conditions, including allergies, and if you are pregnant or plan to become pregnant or if you are breastfeeding or plan to breastfeed. Tell your healthcare provider or pharmacist about any prescription and over-the-counter medicines you are taking or plan to take, including natural or herbal remedies. Praluent can cause serious side effects, including allergic reactions that can be severe and require treatment in a hospital. Call your healthcare provider or go to the nearest hospital emergency room right away if you have any symptoms of an allergic reaction including a severe rash, redness, severe itching, a swollen face, or trouble breathing. The most common side effects of Praluent include: redness, itching, swelling, or pain/tenderness at the injection site, symptoms of the common cold, and flu or flu-like symptoms. Tell your healthcare provider if you have any side effect that bothers you or that does not go away. Talk to your doctor about the right way to prepare and give yourself a Praluent injection and follow the "Instructions for Use" that comes with Praluent. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088. About Sanofi Sanofi, a global healthcare leader, discovers, develops and distributes therapeutic solutions focused on patients' needs. Sanofi is organized into five global business units: Diabetes and Cardiovascular, General Medicines and Emerging Markets, Sanofi Genzyme, Sanofi Pasteur and Consumer Healthcare. Sanofi is listed in Paris (EURONEXT: SAN) and in New York (NYSE: SNY). About Regeneron Pharmaceuticals, Inc. Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents life-transforming medicines for people with serious diseases. Founded and led by physician-scientists for the past 30 years, our unique ability to repeatedly and consistently translate science into medicine has led to six FDA-approved treatments and over a dozen product candidates, all of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye disease, heart disease, allergic and inflammatory diseases, pain, cancer, and infectious and rare diseases. Regeneron is accelerating and improving the traditional drug development process through its unique VelociSuite® technologies and ambitious initiatives such as The Regeneron Genetics Center, one of the largest genetics sequencing efforts in the world. For additional information about the company, please visit www.regeneron.com or follow @Regeneron on Twitter. Sanofi Forward-Looking Statements This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts. These statements include projections and estimates regarding the marketing and other potential of the product, or regarding potential future revenues from the product. Forward-looking statements are generally identified by the words "expects", "anticipates", "believes", "intends", "estimates", "plans" and similar expressions. Although Sanofi's management believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Sanofi, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include among other things, unexpected regulatory actions or delays, or government regulation generally, that could affect the availability or commercial potential of the product, the absence of guarantee that the product will be commercially successful, the uncertainties inherent in research and development, including future clinical data and analysis of existing clinical data relating to the product, including post marketing, unexpected safety, quality or manufacturing issues, competition in general, risks associated with intellectual property and any related litigation and the ultimate outcome of such litigation, and volatile economic conditions, as well as those risks discussed or identified in the public filings with the SEC and the AMF made by Sanofi, including those listed under "Risk Factors" and "Cautionary Statement Regarding Forward-Looking Statements" in Sanofi's annual report on Form 20-F for the year ended December 31, 2016. Other than as required by applicable law, Sanofi does not undertake any obligation to update or revise any forward-looking information or statements. Regeneron Forward-Looking Statements and Use of Digital Media This news release includes forward-looking statements that involve risks and uncertainties relating to future events and the future performance of Regeneron Pharmaceuticals, Inc. ("Regeneron" or the "Company"), and actual events or results may differ materially from these forward-looking statements. Words such as "anticipate," "expect," "intend," "plan," "believe," "seek," "estimate," variations of such words, and similar expressions are intended to identify such forward-looking statements, although not all forward-looking statements contain these identifying words. These statements concern, and these risks and uncertainties include, among others, risks associated with intellectual property of other parties and pending or future litigation relating thereto, including the patent litigation relating to Praluent® (alirocumab) Injection, the permanent injunction granted by the United States District Court for the District of Delaware that, if upheld on appeal, would prohibit Regeneron and Sanofi from marketing, selling, or commercially manufacturing Praluent in the United States, the outcome of any appeals regarding such injunction, the ultimate outcome of such litigation, and the impact any of the foregoing may have on Regeneron's business, prospects, operating results, and financial condition; the nature, timing, and possible success and therapeutic applications of Regeneron's products, product candidates, and research and clinical programs now underway or planned, including without limitation Praluent; unforeseen safety issues and possible liability resulting from the administration of products (including without limitation Praluent) and product candidates in patients; serious complications or side effects in connection with the use of Regeneron's products and product candidates in clinical trials, such as the ODYSSEY OUTCOMES trial prospectively assessing the potential of Praluent to demonstrate cardiovascular benefit; ongoing regulatory obligations and oversight impacting Regeneron's marketed products (such as Praluent), research and clinical programs, and business, including those relating to the enrollment, completion, and meeting of the relevant endpoints of post-approval studies (such as the ODYSSEY OUTCOMES trial); determinations by regulatory and administrative governmental authorities which may delay or restrict Regeneron's ability to continue to develop or commercialize Regeneron's products and product candidates; the likelihood, timing, and scope of possible regulatory approval and commercial launch of Regeneron's late-stage product candidates and new indications for marketed products; competing drugs and product candidates that may be superior to Regeneron's products and product candidates; uncertainty of market acceptance and commercial success of Regeneron's products and product candidates and the impact of studies (whether conducted by Regeneron or others and whether mandated or voluntary) on the commercial success of Regeneron's products and product candidates; the ability of Regeneron to manufacture and manage supply chains for multiple products and product candidates; coverage and reimbursement determinations by third-party payers, including Medicare and Medicaid; unanticipated expenses; the costs of developing, producing, and selling products; the ability of Regeneron to meet any of its sales or other financial projections or guidance and changes to the assumptions underlying those projections or guidance; and the potential for any license or collaboration agreement, including Regeneron's agreements with Sanofi, Bayer HealthCare LLC, and Teva Pharmaceutical Industries Ltd. (or their respective affiliated companies, as applicable), to be cancelled or terminated without any further product success. A more complete description of these and other material risks can be found in Regeneron's filings with the United States Securities and Exchange Commission, including its Form 10-K for the year ended December 31, 2016 and its Form 10-Q for the quarterly period ended March 31, 2017. Any forward-looking statements are made based on management's current beliefs and judgment, and the reader is cautioned not to rely on any forward-looking statements made by Regeneron. Regeneron does not undertake any obligation to update publicly any forward-looking statement, including without limitation any financial projection or guidance, whether as a result of new information, future events, or otherwise. Regeneron uses its media and investor relations website and social media outlets to publish important information about the Company, including information that may be deemed material to investors. Financial and other information about Regeneron is routinely posted and is accessible on Regeneron's media and investor relations website (http://newsroom.regeneron.com) and its Twitter feed (http://twitter.com/regeneron).


Data presented at the 77th Scientific Sessions of the American Diabetes Association (ADA) Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Sanofi today announced positive results from two Phase 3b/4 ODYSSEY-DM trials in patients with diabetes. In the studies, Praluent® (alirocumab) when administered on top of maximally tolerated doses (MTD) of statins significantly reduced low-density lipoprotein cholesterol (LDL-C), the primary endpoint of the ODYSSEY-DM INSULIN study, and was superior to usual care in reducing non-high-density lipoprotein cholesterol (non-HDL-C), the primary endpoint of the ODYSSEY-DM DYSLIPIDEMIA study. Both studies also found that a majority of patients reached their lipid goals with Praluent 75 mg every two weeks, with an overall safety profile comparable to the ODYSSEY Phase 3 program. The results were unveiled today as part of the official symposium of the 77th Scientific Sessions of the American Diabetes Association (ADA) in San Diego, CA, titled, "Inhibition of PCSK9 in Dyslipidemia Patients with Diabetes." The data were also featured in the official ADA Scientific Sessions Advance program. "Patients with long-standing diabetes, including insulin-treated patients, are at high risk of cardiovascular disease," said Lawrence Leiter, M.D., chair of the ODYSSEY-DM Steering Committee and director of the Lipid Clinic at the Li Ka Shing Knowledge Institute at St. Michael's Hospital, University of Toronto, Canada. "The positive results from ODYSSEY-DM INSULIN provide valuable information on the efficacy and safety of Praluent in this high cardiovascular risk group." Most people with diabetes will develop atherosclerotic cardiovascular disease (ASCVD). Despite current standard of care, nearly 70 percent of people age 65 or older with diabetes die from some form of heart disease; and 16 percent die of stroke. "Mixed dyslipidemia is common in people with type 2 diabetes and further increases CV risk, and yet it is difficult to treat with available therapies," said Robert Henry, M.D., member of the ODYSSEY-DM Steering Committee, and Director of the Center for Metabolic Research at the VA San Diego Healthcare System. "The results of ODYSSEY-DM DYSLIPIDEMIA showed that in a real-world setting, Praluent, on top of maximally tolerated doses of statins, significantly reduced non-HDL-C, another measure of bad cholesterol, and was superior to usual care. Based on these results, Praluent may be another option for physicians who need to further help their diabetes patients with clinical ASCVD manage their lipid profiles." In ODYSSEY-DM INSULIN, patients were randomized to Praluent 75 mg every two weeks or placebo in addition to MTD statins. The Praluent dose was adjusted at week 12 to 150 mg every two weeks if their LDL-C was greater than or equal to 70 mg/dL at week 8. Approximately 80 percent of patients reached their LDL-C goals with Praluent 75 mg every two weeks in this study. In ODYSSEY-DM DYSLIPIDEMIA, patients were randomized to Praluent 75 mg every two weeks or usual care in addition to MTD statins. The Praluent dose was adjusted at week 12 to 150 mg every two weeks if their non-HDL-C was greater than or equal to 100 mg/dL at week 8. Approximately 64 percent of patients reached their lipid goals with the Praluent 75 mg dose. ODYSSEY-DM INSULIN was a randomized, double blind, placebo-controlled, multicenter study that evaluated Praluent in 517 people with type 1 and type 2 diabetes on insulin with high CV risk and hypercholesterolemia who took MTD statins. The primary endpoint was percent change in calculated LDL-C from baseline to week 24. Results in the type 2 diabetes study population (n=441) were presented at ADA and showed: ODYSSEY-DM DYSLIPIDEMIA was a randomized, open-label, parallel-group study designed to evaluate the superiority of Praluent versus usual care in 413 people with type 2 diabetes and mixed dyslipidemia at high CV risk, not adequately controlled with MTD statins. The primary endpoint was percent change in non-HDL-C from baseline to week 24. Non-HDL-C is calculated as total cholesterol minus high-density lipoprotein cholesterol, and provides a single index of all the potentially atherogenic, apolipoprotein (apo) B-containing lipoproteins, including LDL, very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and lipoprotein(a). In the previously reported results from the ODYSSEY LONG TERM study in which all patients were treated with Praluent 150 mg on top of MTD statins, Praluent reduced LDL-C by 60 percent from baseline in patients with diabetes (n=545) at week 24. The recommended starting dose of Praluent is 75 mg administered subcutaneously every 2 weeks, or alternatively 300 mg every 4 weeks (monthly) for patients who prefer less frequent dosing. The majority of patients taking Praluent achieve sufficient LDL-C reduction with the 75 mg dose. If the LDL-C response is inadequate, the dosage may be adjusted to the maximum dosage of 150 mg administered every 2 weeks. Praluent inhibits the binding of PCSK9 (proprotein convertase subtilisin/kexin type 9) to the LDL receptor and thereby increases the number of available LDL receptors on the surface of liver cells, which results in lower LDL-C levels in the blood. Praluent is approved in more than 50 countries worldwide, including the U.S., Japan, Canada, Switzerland, Mexico and Brazil, as well as the European Union (EU). In the U.S., Praluent is approved for use as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic CV disease, who require additional lowering of LDL-C. In the EU, Praluent is approved for the treatment of adult patients with primary hypercholesterolemia (HeFH and non-familial) or mixed dyslipidemia as an adjunct to diet: a) in combination with a statin, or statin with other lipid-lowering therapies in patients unable to reach their LDL-C goals with the maximally-tolerated statin or b) alone or in combination with other lipid-lowering therapies for patients who are statin intolerant, or for whom a statin is contraindicated. The effect of Praluent on CV morbidity and mortality has not yet been determined. ODYSSEY OUTCOMES is prospectively evaluating the effect of Praluent on the occurrence of CV events in approximately 18,000 patients who have experienced an acute coronary syndrome. This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. Important Safety Information for the U.S. Do not use PRALUENT if you are allergic to alirocumab or to any of the ingredients in PRALUENT. Before you start using PRALUENT, tell your healthcare provider about all your medical conditions, including allergies, and if you are pregnant or plan to become pregnant or if you are breastfeeding or plan to breastfeed. Tell your healthcare provider or pharmacist about any prescription and over-the-counter medicines you are taking or plan to take, including natural or herbal remedies. PRALUENT can cause serious side effects, including allergic reactions that can be severe and require treatment in a hospital. Call your healthcare provider or go to the nearest hospital emergency room right away if you have any symptoms of an allergic reaction including a severe rash, redness, severe itching, a swollen face, or trouble breathing. The most common side effects of PRALUENT include: redness, itching, swelling, or pain/tenderness at the injection site, symptoms of the common cold, and flu or flu-like symptoms. Tell your healthcare provider if you have any side effect that bothers you or that does not go away. Talk to your doctor about the right way to prepare and give yourself a PRALUENT injection and follow the "Instructions for Use" that comes with Praluent. You are encouraged to report negative side effects of prescription drugs to the FDA. Sanofi, a global healthcare leader, discovers, develops and distributes therapeutic solutions focused on patients' needs. Sanofi is organized into five global business units: Diabetes and Cardiovascular, General Medicines and Emerging Markets, Sanofi Genzyme, Sanofi Pasteur and Consumer Healthcare. Sanofi is listed in Paris (EURONEXT: SAN) and in New York (NYSE: SNY). Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents life-transforming medicines for people with serious diseases. Founded and led by physician-scientists for the past 30 years, our unique ability to consistently translate science into medicine has led to six FDA-approved treatments and over a dozen product candidates, all of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye disease, heart disease, allergic and inflammatory diseases, pain, cancer, and infectious and rare diseases. Regeneron is accelerating and improving the traditional drug development process through its unique VelociSuite® technologies and ambitious initiatives such as The Regeneron Genetics Center, one of the largest genetics sequencing efforts in the world. For additional information about the company, please visit www.regeneron.com or follow @Regeneron on Twitter. This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts. These statements include projections and estimates regarding the marketing and other potential of the product, or regarding potential future revenues from the product. Forward-looking statements are generally identified by the words "expects", "anticipates", "believes", "intends", "estimates", "plans" and similar expressions. Although Sanofi's management believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Sanofi, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include among other things, unexpected regulatory actions or delays, or government regulation generally, that could affect the availability or commercial potential of the product, the absence of guarantee that the product will be commercially successful, the uncertainties inherent in research and development, including future clinical data and analysis of existing clinical data relating to the product, including post marketing, unexpected safety, quality or manufacturing issues, competition in general, risks associated with intellectual property and any related future litigation and the ultimate outcome of such litigation, and volatile economic conditions, as well as those risks discussed or identified in the public filings with the SEC and the AMF made by Sanofi, including those listed under "Risk Factors" and "Cautionary Statement Regarding Forward-Looking Statements" in Sanofi's annual report on Form 20-F for the year ended December 31, 2016. Other than as required by applicable law, Sanofi does not undertake any obligation to update or revise any forward-looking information or statements. Regeneron Forward-Looking Statements and Use of Digital Media This news release includes forward-looking statements that involve risks and uncertainties relating to future events and the future performance of Regeneron Pharmaceuticals, Inc. ("Regeneron" or the "Company"), and actual events or results may differ materially from these forward-looking statements. Words such as "anticipate," "expect," "intend," "plan," "believe," "seek," "estimate," variations of such words, and similar expressions are intended to identify such forward-looking statements, although not all forward-looking statements contain these identifying words. These statements concern, and these risks and uncertainties include, among others, risks associated with intellectual property of other parties and pending or future litigation relating thereto, including the patent litigation relating to Praluent® (alirocumab) Injection, the permanent injunction granted by the United States District Court for the District of Delaware that, if upheld on appeal, would prohibit Regeneron and Sanofi from marketing, selling, or commercially manufacturing Praluent in the United States, the outcome of any appeals regarding such injunction, the ultimate outcome of such litigation, and the impact any of the foregoing may have on Regeneron's business, prospects, operating results, and financial condition; the nature, timing, and possible success and therapeutic applications of Regeneron's products, product candidates, and research and clinical programs now underway or planned, including without limitation Praluent; unforeseen safety issues and possible liability resulting from the administration of products (including without limitation Praluent) and product candidates in patients; serious complications or side effects in connection with the use of Regeneron's products and product candidates in clinical trials, such as the ODYSSEY OUTCOMES trial prospectively assessing the potential of Praluent to demonstrate cardiovascular benefit; ongoing regulatory obligations and oversight impacting Regeneron's marketed products (such as Praluent), research and clinical programs, and business, including those relating to the enrollment, completion, and meeting of the relevant endpoints of post-approval studies (such as the ODYSSEY OUTCOMES trial); determinations by regulatory and administrative governmental authorities which may delay or restrict Regeneron's ability to continue to develop or commercialize Regeneron's products and product candidates; the likelihood, timing, and scope of possible regulatory approval and commercial launch of Regeneron's late-stage product candidates and new indications for marketed products; competing drugs and product candidates that may be superior to Regeneron's products and product candidates; uncertainty of market acceptance and commercial success of Regeneron's products and product candidates and the impact of studies (whether conducted by Regeneron or others and whether mandated or voluntary) on the commercial success of Regeneron's products and product candidates; the ability of Regeneron to manufacture and manage supply chains for multiple products and product candidates; coverage and reimbursement determinations by third-party payers, including Medicare and Medicaid; unanticipated expenses; the costs of developing, producing, and selling products; the ability of Regeneron to meet any of its sales or other financial projections or guidance and changes to the assumptions underlying those projections or guidance; and the potential for any license or collaboration agreement, including Regeneron's agreements with Sanofi, Bayer HealthCare LLC, and Teva Pharmaceutical Industries Ltd. (or their respective affiliated companies, as applicable), to be cancelled or terminated without any further product success. A more complete description of these and other material risks can be found in Regeneron's filings with the United States Securities and Exchange Commission, including its Form 10-K for the year ended December 31, 2016 and its Form 10-Q for the quarterly period ended March 31, 2017. Any forward-looking statements are made based on management's current beliefs and judgment, and the reader is cautioned not to rely on any forward-looking statements made by Regeneron. Regeneron does not undertake any obligation to update publicly any forward-looking statement, including without limitation any financial projection or guidance, whether as a result of new information, future events, or otherwise. Regeneron uses its media and investor relations website and social media outlets to publish important information about the Company, including information that may be deemed material to investors. Financial and other information about Regeneron is routinely posted and is accessible on Regeneron's media and investor relations website (http://newsroom.regeneron.com) and its Twitter feed (http://twitter.com/regeneron). To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/regeneron-and-sanofi-announce-positive-results-from-first-dedicated-studies-evaluating-praluent-alirocumab-in-individuals-with-diabetes-and-hypercholesterolemia-300472008.html


Between 1999 to 2014, there was a decline in average systolic blood pressure, smoking, and predicted cardiovascular risk of 20 percent or greater among high-income U.S. adults, but these levels remained unchanged in adults with incomes at or below the federal poverty level, according to a study published by JAMA Cardiology. Large improvements in the control of risk factors for cardiovascular disease have been achieved in the United States, but it remains unclear whether adults in all socioeconomic levels have benefited equally. Ayodele Odutayo, M.D., of the Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, and University of Oxford, England, and colleagues conducted a study using data on adults 40 to 79 years of age (n = 17,199) without established cardiovascular disease from the 1999 to 2014 National Health and Nutrition Examination Survey. Socioeconomic status was based on the family income to poverty ratio and participants were divided into groups of either high income, middle income, or at or below the federal poverty level. The researchers found that for adults with incomes at or below the federal poverty level, there was little evidence of a change in these outcomes across survey years: percentage with predicted absolute cardiovascular risk of 20 percent or more, 14.9 percent in 1999-2004, 16.5 percent in 2011-2014; average systolic blood pressure, 127.6 mm Hg in 1999-2004, 126.8 mm Hg in 2011-2014; and smoking, 36.5 percent in 1999-2004, 36 percent in 2011-2014. For adults in the high-income group, these measures decreased across survey years: cardiovascular risk 20 percent or greater, 12 percent in 1999-2004, 9.5 percent in 2011-2014; systolic blood pressure, 126 mm Hg in 1999-2004, 122.3 mm Hg in 2011-2014; and smoking, 14.1 percent in 1999-2004, 8.8 percent in 2011-2014. Trends in the percentage of adults with diabetes and the average total cholesterol level did not vary by income. Limitations of the study include that the researchers performed an analysis of multiple cross-sectional surveys and cannot establish a causal association between income and cardiovascular risk factors. "Taken together, recent gains in the control of cardiovascular risk factors in the United States have not benefited adults in all socioeconomic strata equally. Renewed efforts are required to reduce income disparities in control of cardiovascular risk factors," the authors write.


News Article | May 9, 2017
Site: www.eurekalert.org

People who have received organ transplants are at higher risk of developing and dying of cancer than the general population. Yet their rates of cancer screening do not meet existing guidelines, a new study has found TORONTO, May 4, 2017--People who have received organ transplants are at higher risk of developing and dying of cancer than the general population. Yet their rates of cancer screening do not meet existing guidelines, a new study has found. The study, published online today in the American Journal of Transplantation, examined the health records of 6,392 patients who had organ transplants in Ontario between 1997 and 2010. "Most of the organ transplant recipients had periods when they were not up-to-date on colorectal, cervical or breast cancer screening," said senior author Dr. Nancy Baxter, a colorectal surgeon at St. Michael's Hospital and senior scientist at the Institute for Clinical Evaluative Sciences. In fact, a sizeable portion of them had no cancer screening at all during the study, said Dr. Baxter. "Many patients don't see cancer screening as a high priority, because their main health concern is their transplant," she said. "Transplant recipients should be aware they have a heightened risk of developing and dying from cancer and should advocate with their health-care providers to be screened." Current cancer screening guidelines for transplant recipients in Canada generally parallel the guidelines for the general population. Researchers identified 6,392 solid organ transplant recipients who were eligible for cancer screening: 4,436 for colorectal cancer screening, 2,252 eligible for cervical cancer screening, and 1,551 eligible for breast cancer screening. Of those, 3,436 (78 per cent), 1,572 (70 per cent), and 1,417 (91per cent) were not continuously screened for colorectal, cervical and breast cancer, respectively. Dr. Sergio Acuna, the study's lead author and a PhD candidate in clinical epidemiology and health-care research at St. Michael's, said transplant recipients who were routinely seeing their family physician were more likely to be screened for cancer than those followed by a transplant specialist alone. Comorbidities--additional conditions including heart disease and diabetes--and life expectancy also had an effect on recipients' likelihood of being screened, according to the authors. The study found that patients with more comorbidities were less likely to be up-to-date with cancer screening. Previous work by Drs. Baxter and Acuna found that people who had organ transplants were three times more likely to die from cancer than the general population and that cancer was a leading cause of death among these patients. It is well known among clinicians and researchers that cancer screening leads to the detection of cancer at early stages, according to Dr. Acuna. "We have evidence of increased incidence of cancer in transplant recipients, we have some good evidence for the performance of screening tests in transplant recipients, and although we have no direct evidence of the effect of treatment on outcomes, it is likely that early detection in this population would lead to improved outcomes," said Dr. Acuna. Although there are no clinical trials demonstrating that this screening benefit applies to organ transplant recipients, it is unlikely to change given that clinical trials require large numbers of people to provide accurate data and the transplant population is relatively small, he said. In another study, Drs. Baxter and Acuna found cancer screening guidelines for this group are inconsistent as is the use of these guidelines. Their review found only 13 sets of clinical practice guidelines--recommendations for optimizing patient care generally based on evidence--for cancer screening of transplant recipients. Most were for kidney transplant recipients as kidneys are the most commonly transplanted organ. Dr. Acuna said this inconsistency could be one reason for low screening rates in this population, and patients and their physicians should be aware of the need for cancer screening. "In Canada, the guidelines are not comprehensive, and there are no specific guidelines for most types of solid organ transplant," he said. "Family doctors, transplant specialists and transplant recipients should all be aware that cancer screening guidelines for the general population should also apply to them or their patients." Today's study received funding from the Canadian Institutes of Health Research. St. Michael's Hospital provides compassionate care to all who enter its doors. The hospital also provides outstanding medical education to future health care professionals in 27 academic disciplines. Critical care and trauma, heart disease, neurosurgery, diabetes, cancer care, care of the homeless and global health are among the hospital's recognized areas of expertise. Through the Keenan Research Centre and the Li Ka Shing International Healthcare Education Centre, which make up the Li Ka Shing Knowledge Institute, research and education at St. Michael's Hospital are recognized and make an impact around the world. Founded in 1892, the hospital is fully affiliated with the University of Toronto. The Institute for Clinical Evaluative Sciences (ICES) is an independent, non-profit organization that uses population-based health information to produce knowledge on a broad range of health care issues. Our unbiased evidence provides measures of health system performance, a clearer understanding of the shifting health care needs of Ontarians, and a stimulus for discussion of practical solutions to optimize scarce resources. ICES knowledge is highly regarded in Canada and abroad, and is widely used by government, hospitals, planners, and practitioners to make decisions about care delivery and to develop policy. For the latest ICES news, follow us on Twitter: @ICESOntario For more information or to arrange an interview, please contact: Deborah Creatura Media Advisor, ICES (o) 416-480-4780 or (c) 647-406-5996 deborah.creatura@ices.on.ca


News Article | September 19, 2017
Site: www.eurekalert.org

Nearly three times that number could have been saved if national progress in child health matched that reached in some states TORONTO, Sept. 19, 2017--India has avoided about 1 million deaths of children under age five since 2005, driven by significant reductions in mortality from pneumonia, diarrhea, tetanus and measles, according to new research published today. Nearly three times that number could have been saved if national progress in child health matched that reached in some states, Dr. Prabhat Jha, head of the Centre for Global Health Research of St. Michael's Hospital in Toronto, wrote in today's issue of The Lancet. A steeper decline in the number of girls dying narrowed a previously observed girl-boy mortality gap, said Dr. Jha, a professor in the Dalla Lana School of Public Health at the University of Toronto. An almost equal number of boys and girls under age five died in 2015. This research is part of the Million Death Study, one of the largest studies of premature deaths in the world. Dr. Jha is the lead investigator of the survey, based in India, where most deaths occur at home and without medical attention. Hundreds of specially trained census staff in India knocked on doors of more than 1.3 million homes to interview household members about deaths. Two physicians independently examined these "verbal autopsies" to establish the most probable cause of death. "You get the truth when you knock on doors and talk to parents," said Dr. Jha. "We knocked on the doors of 100,000 homes where children died. If the health system failed these families, they will tell you all about it. These are far more reliable numbers than models or projections from small studies." The study found a 3.3 per cent annual decline in mortality rates of neonates (infants less than one month old) and 5.4 per cent for those ages one month to 59 months. The declines accelerated starting in 2005 and were fastest between 2010 and 2015, and in urban areas and richer states. Per 1,000 live births, the mortality rates among neonates fell from 45 in 2000 to 27 in 2015. The one-59 month mortality rate fell from 45.2 to 19.6. Looking at specific causes of death, mortality rates from neonatal tetanus and measles fell by at least 90 per cent, neonatal infection and birth trauma fell more than 66 per cent. For children ages one to 59 months, mortality rates from pneumonia and diarrhea fell more than 60 per cent. About 6 million children die around the world each year and progress in reducing that number depends greatly on India, which accounts for about a fifth of the deaths. About 29 million Indian children died between 2000 and 2015. Had the mortality rates of 2000 continued unchanged, about 39 million children would have died. The authors noted that in the last decade the government of India has modestly increased its traditionally low level of public spending on health. The government launched a program to encourage women to give birth in hospitals and for children to have a second dose of measles vaccine. Dr. Jha said that to meet the United Nation's Sustainable Development Goals of halving its child mortality rates by 2030, India must maintain its current trajectory for children ages one to 59 months and accelerate declines in neonatal mortality. Reducing the number of neonatal deaths will require efforts to reduce deaths caused by premature delivery and low birthweights, especially in poorer states, he said. Both are strongly linked to largely modifiable maternal and prenatal factors such as health care during pregnancy, education, nutrition, anemia and tobacco use. In an accompanying commentary for The Lancet, leading scientists from Bangladesh and Tanzania wrote that the "Million Death Study can be a model for other countries where vital registration systems are still fragmented." This work received funding from the U.S. National Institutes of Health, the Disease Control Priorities Network, the Maternal and Child Epidemiology Estimation Group and the University of Toronto. St. Michael's Hospital provides compassionate care to all who enter its doors. The hospital also provides outstanding medical education to future health care professionals in more than 29 academic disciplines. Critical care and trauma, heart disease, neurosurgery, diabetes, cancer care, care of the homeless and global health are among the hospital's recognized areas of expertise. Through the Keenan Research Centre and the Li Ka Shing International Healthcare Education Center, which make up the Li Ka Shing Knowledge Institute, research and education at St. Michael's Hospital are recognized and make an impact around the world. Founded in 1892, the hospital is fully affiliated with the University of Toronto. For more information, or to interview Dr. Jha, please contact: Press Conference (by invitation, contact Prabha Sati) from 10 a.m. to 1 p.m., Wednesday, Sept. 20, 2017, at The Dome, Vivanta by Taj Ambassador Hotel, Subramania Bharti Marg, (Near Khan Market), New Delhi


Canton J.,Hospital for Sick Children | Neculai D.,Hospital for Sick Children | Grinstein S.,Hospital for Sick Children | Grinstein S.,University of Toronto | Grinstein S.,Li Ka Shing Knowledge Institute
Nature Reviews Immunology | Year: 2013

Scavenger receptors were originally identified by their ability to recognize and to remove modified lipoproteins; however, it is now appreciated that they carry out a striking range of functions, including pathogen clearance, lipid transport, the transport of cargo within the cell and even functioning as taste receptors. The large repertoire of ligands recognized by scavenger receptors and their broad range of functions are not only due to the wide range of receptors that constitute this family but also to their ability to partner with various co-receptors. The ability of individual scavenger receptors to associate with different co-receptors makes their responsiveness extremely versatile. This Review highlights recent insights into the structural features that determine the function of scavenger receptors and the emerging role that these receptors have in immune responses, notably in macrophage polarization and in the pathogenesis of diseases such as atherosclerosis and Alzheimer's disease. © 2013 Macmillan Publishers Limited. All rights reserved.


Fairn G.D.,Li Ka Shing Knowledge Institute | Grinstein S.,Li Ka Shing Knowledge Institute
Trends in Immunology | Year: 2012

Phagocytosis mediates the clearance of apoptotic bodies and also the elimination of microbial pathogens. The nascent phagocytic vacuole formed upon particle engulfment lacks microbicidal and degradative activity. These capabilities are acquired as the phagosome undergoes maturation; a progressive remodeling of its membrane and contents that culminates in the formation of phagolysosomes. Maturation entails orderly sequential fusion of the phagosomal vacuole with specialized endocytic and secretory compartments. Concomitantly, the phagosomal membrane undergoes both inward and outward vesiculation and tubulation followed by fission, thereby recycling components and maintaining its overall size. Here, we summarize what is known about the molecular machinery that governs this complex metamorphosis of phagosome maturation. © 2012 Elsevier Ltd.


Slutsky A.S.,Li Ka Shing Knowledge Institute
American journal of respiratory and critical care medicine | Year: 2015

Mechanical ventilation is a life-saving therapy that catalyzed the development of modern intensive care units. The origins of modern mechanical ventilation can be traced back about five centuries to the seminal work of Andreas Vesalius. This article is a short history of mechanical ventilation, tracing its origins over the centuries to the present day. One of the great advances in ventilatory support over the past few decades has been the development of lung-protective ventilatory strategies, based on our understanding of the iatrogenic consequences of mechanical ventilation such as ventilator-induced lung injury. These strategies have markedly improved clinical outcomes in patients with respiratory failure.

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