postMONARCH: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Compare the Efficacy of Abemaciclib plus Fulvestrant to Placebo plus Fulvestrant in Participants with HR+, HER2-, Advanced or Metastatic Breast Cancer Following Progression on a CDK4 & 6 Inhibitor and Endocrine Therapy - postMONARCH
A Randomized, Phase 3, Double-blind Trial Comparing the Effect of the Addition of Tirzepatide versus Placebo in Patients with Type 2 Diabetes Inadequately Controlled on Insulin Glargine with or without Metformin (SURPASS-5) - SURPASS-5
Insights into the role of HDX-MS in medicinal chemistry
作者: Espada, Alfonso ; Broughton, Howard
In the fast-moving pharmaceutical industry where new drug discovery technologies and therapeutic modalities are applied almost daily, it is expected that data science will improve the efficiency in the identification of drug targets, find good chem. scaffolds from data libraries, guide chem. synthesis and move the goalposts to select drug candidates. However, there are challenges to overcome associated with this process. A case in point is the vast number of protein-ligand interactions where the link between biochem. behavior and structural biol. is not yet understood. Although computational approaches (e.g., docking methods, mol. dynamics simulations etc.) can hypothesize the bound poses of ligands for a targeted protein, these predicted events must be validated by biophys./structural approaches. In this context, Hydrogen/deuterium-exchange coupled to mass spectrometry (HDX-MS) is expected to continue developing as a method to study the characterization of protein dynamics following ligand binding in solution (where "ligand" could be a protein partner, a natural substrate, a peptide, or a small mol.). In this presentation we will discuss the broad applicability of HDX-MS to characterize the dynamics of a set of protein-protein interactions in solution (e.g., to examine the protein alone and in complex with its receptor) and to identify how the amide hydrogen bonding network of ligands and the protein forms are altered by binding interactions. These data will be used to probe proteins as druggable targets, validate direct binding events from mol. dynamics simulation studies and to complement structural biol. information.
Challenging the sensitivity of HDX/MS with a large heterodimeric protein receptor: Characterization of the binding interactions of new generation integrin α4β7 inhibitors
作者: Perez, Francisco ; Broughton, Howard ; Carrillo, Juan J. ; Vieth, Michal ; Russell, Anna maria ; Afshar, Sepideh ; Espada, Alfonso
Integrins are heterodimeric receptor mols. that function in cell adhesion and signaling, with key roles in multiple sclerosis, inflammation and cancer, and as a result are important drug targets. Currently, 3 of the 24 known human integrins have emerged as attractive targets because the effect of their inactivation has been probed by monoclonal antibodies, peptides and small mol. potential integrin inhibitors. Highly effective new antibodies and peptides targeting α4β7 have been discovered and have shown significant pre-clin. efficacy for the treatment of inflammatory bowel diseases. A case in point are the monomeric/dimeric disulfide-linked cyclic peptides PTG-100, which have recently shown major benefits in human studies. Despite this relevant finding, the characterization of the binding epitope of these new generation integrin inhibitors on the α4β7 receptor is still elusive. In this study, we report for the first time the mol. characterization of the binding interactions of clin. therapeutic disulfide-linked cyclic peptides PTG-100 against the integrin α4β7 receptor as probed by HDX/MS and computational approaches. The results of this study are of paramount importance to get a deeper insight into the involvement of α4β7 in autoimmune diseases and to guide the discovery of new chemotypes as inhibitors of this integrin receptor.
2019·Journal of Diabetes Research & Clinical Metabolism
Treatment persistence behaviours in patients with type 2 diabetes (T2DM) after initiation of basal insulin: an exploratory analysis from a spanish real-world sample
作者: De Santos, Miriam Rubio ; Hadjiyianni, Irene ; Perez-Nieves, Magaly ; Cao, Dachuang ; Ivanova, Jasmina ; Dilla, Tatiana ; Martinez, Juan Jose Gorgojo
Background: The real-world effectiveness of insulin therapy is influenced by poor treatment persistence. An international cross-sectional survey of people with type 2 diabetes mellitus (T2DM) was conducted to assess experiences before, during, and after basal insulin initiation, and to describe reasons for early nonpersistence with insulin therapy. A sub-anal. based on the Spanish cohort and notable between-group comparisons are presented. Patients and methods: Responders to an online survey in seven countries were classified as continuers (no gap in insulin treatment ≥7 days), interrupters (interrupted therapy for ≥7 days within first 6 mo, then restarted) and discontinuers (stopped insulin therapy within first 6 mo and did not restart before the survey). Data from the Spanish subpopulation were analyzed in combination and sep. for the three persistence pattern groups. Results: Of 942 global respondents, 150 (50 continuers, 50 interrupters, 50 discontinuers) were from Spain, with a mean age of 36 years and a mean of 6 years since first T2DM diagnosis. Reasons contributing to insulin continuation were improved glycemic control (70%) followed by improved phys. feeling and the convenience of insulin relative to other diabetes treatments (both 46%). Common reasons for interruption were weight gain (46%), hypoglycemia and the inconvenience of using insulin (both 40%). Most common reasons for discontinuation were weight gain and pain from injections (both 40%) followed by the dislike/ fear of needles (34%). Conclusion: The benefits of basal insulin therapy motivated continuers to persist with the treatment, whereas experienced or anticipated side effects and injection concerns contributed to interruption and discontinuation. Understanding factors affecting persistence patterns among Spanish patients with T2DM may help clinicians improve successful continuation of basal insulin therapy.
GENEVA, Sept. 28, 2022 /PRNewswire/ -- On World Heart Day, the World Heart Federation (WHF) is calling for urgent action on climate change and health inequity, saying millions more lives are now at risk from cardiovascular disease, which is still the world's biggest killer.
Climate change and air pollution are responsible for 25% of deaths from cardiovascular disease, killing 7 million people annually. These deaths and the wider impacts of climate change disproportionately affect vulnerable populations.
Cardiovascular disease, the world’s largest killer, claims 19 million lives every year. Learn more at worldheartday.org
Everyone is encouraged to get involved in World Heart Day to maximise heart health
Professor Fausto Pinto, President of WHF: "Millions of already vulnerable people are doubly exposed to extreme weather events and limited access to healthcare. World leaders must step up efforts on the two biggest threats of our time: climate change and global health inequity."
Alongside the World Health Organisation (WHO), WHF is calling on governments, civil society, and global industry to meet net-zero targets, to tackle global warming and curb air pollution, and to deliver healthcare access for all.
"Climate change is not about polar bears or icebergs anymore. It's about people's health, especially poor people's health. We need to reduce emissions in the name of health otherwise we will see more and more disasters and more suffering everywhere," says Dr Maria Neira, Director of Department of Environment, Climate Change and Health at WHO.
A recent global survey by WHF revealed that people perceive social inequality and access to healthcare as the second most serious issue for cardiovascular, with health and climate change and air pollution ranked third. 80% of respondents highlighted government action as essential to reducing the burden of CVD.
WHF is also urging healthcare providers to issue regular reminders to at-risk groups about the dangers of extreme weather events, including tips on managing excessive heat events.
"We know what works in prevention and in treatment of the world's biggest killer. It is time for scaled up implementation and shared responsibility." Prof. Pinto adds.
About World Heart Day 2022
Everyone is encouraged to get involved in World Heart Day and to learn more about better heart health. For more information about World Heart Day, visit world-heart-federation.org/world-heart-day.
Join the conversation using the #UseHeart hashtag and post builder (world-heart-federation.org/world-heart-day/get-involved/create-and-share).
Notes to Editors
Media Contact: Borjana Pervan, Strategy and Communication Director, World Heart Federation
[email protected], +41 22 807 03 23
About Professor Fausto Pinto, President of WHF
Professor Fausto Pinto is the current President of the World Heart Federation and Past-President of European Society of Cardiology. He is currently the Dean of the Faculty of Medicine of the University of Lisbon (Lisbon, Portugal), and Full Professor of Cardiology. He is also the Head of the Cardiology Department and of the Heart and Vascular Department of Santa Maria University Hospital, CHULN E.P.E. Follow Professor Pinto on Twitter
About World Heart Day
World Heart Day is celebrated each year on 29 September to raise awareness and mobilize international action against cardiovascular disease (CVD), the leading cause of death on the planet. It is the global initiative under which individuals, governments and the entire heart community come together to engage in fun activities, increase public education, and advocate for universal access to CVD prevention, detection and treatment. For more information, visit .
About the World Heart Federation
The World Heart Federation (WHF) is an umbrella organisation representing the global cardiovascular community, uniting patient, medical, scientific, and civil society groups. Together with its Members, WHF influences policies, shares knowledge and inspires behaviour change to achieve heart health for everyone. For more information, visit .
About Boehringer Ingelheim and Lilly Alliance
The Boehringer Ingelheim and Lilly Alliance are driven to transform care for people with cardio-renal-metabolic conditions, a group of interconnected disorders that affect more than one billion people worldwide and are a leading cause of death.
The cardiovascular, renal and metabolic systems are interconnected, and share many of the same risk factors and pathological pathways along the disease continuum. Dysfunction in one system may accelerate the onset of others, resulting in progression of interconnected diseases such as type 2 diabetes, cardiovascular disease, heart failure, and kidney disease, which in turn leads to an increased risk of cardiovascular death. Conversely, improving the health of one system can lead to positive effects throughout the others.
This World Heart Day, they are proud to continue to support the World Heart Federation. Through their research and treatments, their goal is to support people's health, restoring the balance between the interconnected cardio-renal-metabolic systems and reducing their risk of serious complications. As part of their commitment to those whose health is jeopardized by cardio-renal-metabolic conditions, they will continue embracing a multidisciplinary approach towards care and focusing our resources on filling treatment gaps.
Servier is a global pharmaceutical group governed by a Foundation. Servier is an independent group that invests over 20% of its brand-name revenue in Research and Development every year. To accelerate therapeutic innovation for the benefit of patients, the Group is committed to open and collaborative innovation with academic partners, pharmaceutical groups, and biotech companies. It also integrates the patient's voice at the heart of its activities.
A leader in cardiology, the ambition of the Servier Group is to become a renowned and innovative player in oncology. Its growth is based on a sustained commitment to cardiovascular and metabolic diseases, oncology, neuroscience and immuno-inflammatory diseases. To promote access to healthcare for all, the Servier Group also offers a range of quality generic drugs covering most pathologies.
As an official global partner for World Heart Day 2022, Servier's support helps raise awareness and encourages individuals, families, communities and governments to drive the CVD agenda and help people live longer, better, more heart-healthy lives.
 In 2022, the World Heart Federation conducted a global pulse survey of 2500 people across 25 countries.
SOURCE World Heart Federation
Results from the Phase III EMPEROR-Preserved trial were presented August 27 at the European Society of Cardiology Congress 20211 and published in The New England Journal of Medicine2
In this clinical first for adults with heart failure with preserved ejection fraction, empagliflozin demonstrated a 21 per cent relative risk reduction in the composite primary endpoint of cardiovascular death or hospitalization2
Approximately 670,000 Canadians are living with heart failure, with nearly 93,000 new diagnoses expected each year3
Empagliflozin also reduced the relative risk of first and recurrent hospitalizations for heart failure by 27 per cent and significantly slowed kidney function decline2
The EMPEROR-Preserved trial included 34 study sites across Canada
BURLINGTON, ON and TORONTO, Aug. 30, 2021 /CNW/ - Full results from the landmark EMPEROR-Preserved Phase III trial demonstrated that empagliflozin showed a 21 per cent relative risk reduction for the composite primary endpoint of cardiovascular death or hospitalization for heart failure in adults with heart failure with preserved ejection fraction (HFpEF) compared with placebo.2 The benefit was independent of ejection fraction or diabetes status,2 establishing empagliflozin as the first and only treatment to significantly improve outcomes for the full spectrum of heart failure patients. The results were presented on August 27, at the European Society of Cardiology (ESC) Congress 20211 and published in The New England Journal of Medicine,2 Boehringer Ingelheim and Eli Lilly and Company (NYSE: LLY) announced.
Key secondary endpoint analyses from the trial showed that empagliflozin also reduced the relative risk of first and recurrent hospitalizations for heart failure by 27 per cent and significantly slowed kidney function decline.2
"Until now, there have been no clinically proven treatment options for patients who have heart failure with a preserved ejection fraction," said Dr. Shelley Zieroth, cardiologist and director of St. Boniface Hospital Heart Failure and Transplant Clinics, in Winnipeg, MB, and a clinical investigator for the EMPEROR-Preserved trial. "Results from the study show that empagliflozin is effective in not only treating heart failure with preserved ejection fraction, but also keeping patients out of hospital and slowing kidney decline – which are key factors for prolonging life and allowing my patients to continue to live well. These findings not only give me hope as a clinician but for my patients who at present have limited options available to them."
Heart failure affects more than 60 million people worldwide.4 In Canada, approximately 670,000 Canadians are currently living with heart failure and nearly 93,000 new cases are diagnosed each year.3 HFpEF, which is also known as diastolic heart failure, comprises half of all heart failure cases.5 HFpEF has been described as the single largest unmet need in cardiovascular medicine based on its prevalence, high morbidity and mortality, and the absence of clinically proven therapies to date.6,7
"Heart failure is a complex, serious health issue and a leading cause of hospitalization," said Waheed Jamal, M.D., Corporate Vice President and Head of CardioMetabolic Medicine, Boehringer Ingelheim. "The risk of death in people with heart failure rises with each hospital admission and with kidney function decline. The landmark EMPEROR-Preserved trial shows that empagliflozin brings significant benefit, which is incredibly exciting and welcome news for both the medical and patient communities."
"These impressive results will bring hope for the millions of people who currently have limited therapeutic options for a very serious, life-threatening condition," said Jeff Emmick, M.D., Ph.D., Vice President, Product Development, Lilly. "Now there is a light at the end of the tunnel. If approved, empagliflozin would become the first clinically proven therapy across the full heart failure spectrum. The results of EMPEROR-Preserved offer an opportunity to fundamentally change the future for people with heart failure."
EMPEROR-Preserved included 5,988 people with heart failure.2 Of these, 4,005 had a left ventricular ejection fraction (LVEF) of 50 per cent or above and 1,983 had a LVEF between 40 and 50 per cent.2 Trial participants were randomly assigned to empagliflozin 10 mg (n=2,997) or placebo (n=2,991) once daily.2 The overall safety data was consistent with previous findings, confirming the well-established safety pro empagliflozin.8
The benefits demonstrated in the EMPEROR-Preserved trial are similar to those in the EMPEROR-Reduced trial, where empagliflozin significantly reduced the relative risk of the composite endpoint of cardiovascular death or hospitalization for heart failure by 25 per cent, compared with placebo, in adults with heart failure with reduced ejection fraction (HFrEF).9 Together, these studies demonstrate the benefits of empagliflozin for patients across the full heart failure spectrum.
About the EMPEROR heart failure studies10,11
The EMPEROR (EMPagliflozin outcomE tRial in patients with chrOnic heaRt failure) chronic heart failure studies were two Phase III, randomized, double-blind trials that investigated once-daily empagliflozin compared to placebo in adults with chronic HFrEF or HFpEF, with or without diabetes:
EMPEROR-Reduced [NCT03057977] investigated the safety and efficacy of empagliflozin in patients with chronic HFrEF.
Primary endpoint: time to first event of adjudicated cardiovascular death or adjudicated hospitalization for heart failure
Number of patients: 3,730; which included 36 study sites in Canada
EMPEROR-Preserved [NCT03057951] investigated the safety and efficacy of empagliflozin in patients with chronic HFpEF.
Primary endpoint: time to first event of adjudicated cardiovascular death or adjudicated hospitalization for heart failure
Number of patients: 5,988; which included 34 study sites in Canada
Link to lay summary
About the EMPOWER program
The Boehringer Ingelheim and Lilly Diabetes Alliance has developed the EMPOWER program to explore the impact of empagliflozin on major clinical cardiovascular and renal outcomes in a spectrum of cardio-renal-metabolic conditions. Cardio-renal-metabolic conditions are the leading cause of mortality worldwide and account for up to 20 million deaths annually.12
Through the EMPOWER program, the Alliance is working to advance knowledge of these interconnected systems and create care which offers integrated, multi-organ benefits. Comprised of nine clinical trials and two real-world evidence studies, EMPOWER reinforces the long-term commitment of the Alliance to improve outcomes for people living with cardio-renal-metabolic conditions. With more than 400,000 adults enrolled worldwide in clinical studies, it is one of the broadest and most comprehensive clinical programs for an SGLT2 inhibitor to date.
About heart failure
Heart failure is a serious condition, that occurs when the heart cannot keep up with its workload, and the body may not get the oxygen that it needs. As the left and right sides of the heart fail, fluid may build up in the lungs, abdomen, or legs.13,14 It is a common condition affecting over 60 million people worldwide and expected to increase as the population ages.4,5 In Canada, approximately 670,000 people are living with heart failure.3 Heart failure is twice as common in people with diabetes.15
There are different types of heart failure. People with left-sided heart failure have either a reduced or a preserved ejection fraction. Ejection fraction is a measurement of the percentage of blood the left ventricle pumps out with each contraction.16 When the heart relaxes, the ventricle refills with blood.
Heart failure with preserved ejection fraction occurs when the left ventricle of the heart is unable to relax and properly fill with blood, resulting in less blood being available to be pumped out to the body.16
Heart failure with reduced ejection fraction occurs when the left ventricle of the heart is not able to contract effectively, which means that the heart cannot pump with enough force, so less blood is pushed out to the body.16
People with heart failure often experience shortness of breath and fatigue, which can severely impact their quality of life.17 Individuals with heart failure often also have impaired kidney function, which can further worsen patient outcomes and quality of life.18
About cardio-renal-metabolic conditions
Boehringer Ingelheim and Lilly are driven to transform care for people with cardio-renal-metabolic conditions, a group of interconnected disorders that affect more than one billion people worldwide and are a leading cause of death.4,12
Through our research and treatments, our goal is to support people's health, restoring the balance between the interconnected cardio-renal-metabolic systems and reducing their risk of serious complications. As part of our commitment to those whose health is jeopardized by cardio-renal-metabolic conditions, we will continue embracing a multidisciplinary approach towards care and focusing our resources on filling treatment gaps.
Empagliflozin (marketed as Jardiance®) is an oral, once-daily, highly selective sodium-glucose cotransporter 2 (SGLT2) inhibitor and the first type 2 diabetes medicine to include cardiovascular death risk reduction data in its label in several countries.19,20,21,22
Empagliflozin is currently indicated for the treatment of adults with insufficiently controlled type 2 diabetes.19,20,21 Additionally, empagliflozin is approved for the treatment of adults with HFrEF in the European Union and the U.S.19,23 Boehringer Ingelheim and Lilly Alliance plan for global regulatory submissions in HFpEF in 2021. Research is ongoing regarding the effects of empagliflozin on hospitalization for heart failure and mortality in post-myocardial infarction (heart attack) patients with high risk of heart failure.24 Empagliflozin is also currently being investigated in chronic kidney disease.25
Boehringer Ingelheim and Eli Lilly and Company
In January 2011, Boehringer Ingelheim and Eli Lilly and Company announced an Alliance that centers on compounds representing several of the largest diabetes treatment classes. Depending on geographies, the companies either co-promote or separately promote the respective molecules each contributing to the Alliance. The Alliance leverages the strengths of two of the world's leading pharmaceutical companies to focus on patient needs. By joining forces, the companies demonstrate their commitment, not only to the care of people with diabetes, but also to investigating the potential to address areas of unmet medical need. Clinical trials have been initiated to evaluate the impact of empagliflozin on people living with heart failure or chronic kidney disease.
About Boehringer Ingelheim (Canada) Ltd.
Boehringer Ingelheim is working on breakthrough therapies that improve the lives of humans and animals. As a leading research-driven biopharmaceutical company, the company creates value through innovation in areas of high unmet medical need. Founded in 1885 and family-owned ever since, Boehringer Ingelheim takes a long-term perspective. Approximately 52,000 employees serve more than 130 markets in the three business areas, Human Pharma, Animal Health and Biopharmaceutical Contract Manufacturing. The Canadian headquarters of Boehringer Ingelheim was established in 1972 in Montreal, Quebec and is now located in Burlington, Ontario. Boehringer Ingelheim employs approximately 600 people across Canada. Learn more at .
About Eli Lilly Canada
Eli Lilly and Company is a global healthcare leader that unites caring with discovery to make life better for people around the world. We were founded more than a century ago by Colonel Eli Lilly, who was committed to creating high quality medicines that meet people's needs, and today we remain true to that mission in all our work. Lilly employees work to discover and bring life-changing medicines to people who need them, improve the understanding and management of disease, and contribute to our communities through philanthropy and volunteerism.
Eli Lilly Canada was established in 1938, the result of a research collaboration with scientists at the University of Toronto, which eventually produced the world's first commercially available insulin. Our work focuses on oncology, diabetes, autoimmunity, neurodegeneration, and pain. To learn more about Lilly Canada, please visit us at .
For our perspective on issues in healthcare and innovation, follow us on twitter @LillyPadCA and @LillyMedicalCA.
SOURCE Boehringer Ingelheim (Canada) Ltd.
Company Codes: NYSE:LLY