The FOURIER trial investigated whether adding evolocumab to statin therapy reduces cardiovascular events. Over 27,000 patients with a history of cardiovascular disease were randomized to receive evolocumab or placebo injections in addition to statin therapy. The primary objective was to determine if evolocumab lowered the risk of major cardiovascular events such as heart attack, stroke, and cardiovascular death. Secondary objectives were to examine the long-term safety and tolerability of evolocumab and investigate the efficacy and safety of achieving very low LDL-cholesterol levels. Results from this outcomes trial could provide evidence on whether PCSK9 inhibition translates to clinical benefit for high-risk patients.
Empagliflozin and Cardiovascular OutcomesUyen Nguyen
1) The EMPA-REG OUTCOME trial evaluated the cardiovascular outcomes of empagliflozin compared to placebo in over 7000 patients with type 2 diabetes at high risk of cardiovascular events.
2) Empagliflozin was found to significantly reduce the risk of the primary composite outcome of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke compared to placebo.
3) Additional benefits observed with empagliflozin included a significant reduction in all-cause mortality, cardiovascular mortality, and hospitalization for heart failure.
This document discusses glucose-lowering therapies and the clinical place of SGLT2 inhibitor agents. It presents the case of a 52-year-old male patient with type 2 diabetes, hypertension, and coronary artery disease. It analyzes adding empagliflozin or sitagliptin to the patient's current metformin regimen and reviews long-term trial data showing empagliflozin's superior effects on HbA1c reduction, weight loss, and hypoglycemia risk reduction compared to glimepiride. The document also discusses empagliflozin's benefits on blood pressure and potential cardioprotective mechanisms of action beyond glycemic control such as reducing cardiac fibrosis. It emphasizes the importance of individual
Beta Blockers in current cardiovascular practice Praveen Nagula
betablockers are the drug of choice for prevention of progression of heart failure with mortality benefit, after the evolution of neurohormonal regulation as pathogenesis of heart failure
- Evolocumab is a fully human monoclonal antibody that reduces LDL cholesterol levels by approximately 60% when used in addition to statin therapy.
- A large clinical trial found that evolocumab significantly reduced the risk of cardiovascular events such as heart attack and stroke in patients with cardiovascular disease. Evolocumab lowered LDL cholesterol levels to less than 70 mg/dL in 87% of patients.
- The benefits of evolocumab in reducing cardiovascular outcomes were consistent across various patient groups and baseline LDL cholesterol levels and were maintained over time with treatment. No significant safety issues were identified with evolocumab.
This document discusses antiplatelet therapy and P2Y12 platelet inhibition. It notes that dual antiplatelet therapy with aspirin and a P2Y12 inhibitor such as clopidogrel, prasugrel, or ticagrelor is the standard treatment for patients with acute coronary syndrome. It reviews the mechanisms of action and pharmacological properties of different antiplatelet drugs. It also summarizes key trials that have evaluated antiplatelet therapies and provides recommendations from guidelines on treatment selection and duration based on a patient's risk of bleeding and thrombosis.
The EMPA-KIDNEY trial aims to evaluate whether empagliflozin can benefit patients with chronic kidney disease (CKD) and cardiovascular disease outcomes in patients with or without diabetes. The trial plans to enroll approximately 6,000 patients with CKD at risk of kidney disease progression, defined as an eGFR of 20-45 mL/min/1.73 m2 or an eGFR of 45-90 mL/min/1.73 m2 with albuminuria above 200 mg/g. Patients will be randomly assigned to receive empagliflozin 10 mg daily or placebo daily in addition to standard of care. The primary outcome is a composite of cardiovascular death, end-stage kidney disease,
1) Bifurcation stenting approaches are based on the angiographic configuration of lesions in the main and side branches. Significant disease (>50% stenosis) in the side branch ostium increases the risk of side branch closure and restenosis.
2) The default approach is one-stent with provisional side branch treatment. Two-stent techniques are used if the side branch has significant disease and high closure risk features.
3) Techniques like crush, culotte, and T-stenting aim to provide full coverage of both branches, but have limitations and risks. Physiologic assessment with IVUS and FFR can help decide if jailed side branches require intervention.
Empagliflozin and Cardiovascular OutcomesUyen Nguyen
1) The EMPA-REG OUTCOME trial evaluated the cardiovascular outcomes of empagliflozin compared to placebo in over 7000 patients with type 2 diabetes at high risk of cardiovascular events.
2) Empagliflozin was found to significantly reduce the risk of the primary composite outcome of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke compared to placebo.
3) Additional benefits observed with empagliflozin included a significant reduction in all-cause mortality, cardiovascular mortality, and hospitalization for heart failure.
This document discusses glucose-lowering therapies and the clinical place of SGLT2 inhibitor agents. It presents the case of a 52-year-old male patient with type 2 diabetes, hypertension, and coronary artery disease. It analyzes adding empagliflozin or sitagliptin to the patient's current metformin regimen and reviews long-term trial data showing empagliflozin's superior effects on HbA1c reduction, weight loss, and hypoglycemia risk reduction compared to glimepiride. The document also discusses empagliflozin's benefits on blood pressure and potential cardioprotective mechanisms of action beyond glycemic control such as reducing cardiac fibrosis. It emphasizes the importance of individual
Beta Blockers in current cardiovascular practice Praveen Nagula
betablockers are the drug of choice for prevention of progression of heart failure with mortality benefit, after the evolution of neurohormonal regulation as pathogenesis of heart failure
- Evolocumab is a fully human monoclonal antibody that reduces LDL cholesterol levels by approximately 60% when used in addition to statin therapy.
- A large clinical trial found that evolocumab significantly reduced the risk of cardiovascular events such as heart attack and stroke in patients with cardiovascular disease. Evolocumab lowered LDL cholesterol levels to less than 70 mg/dL in 87% of patients.
- The benefits of evolocumab in reducing cardiovascular outcomes were consistent across various patient groups and baseline LDL cholesterol levels and were maintained over time with treatment. No significant safety issues were identified with evolocumab.
This document discusses antiplatelet therapy and P2Y12 platelet inhibition. It notes that dual antiplatelet therapy with aspirin and a P2Y12 inhibitor such as clopidogrel, prasugrel, or ticagrelor is the standard treatment for patients with acute coronary syndrome. It reviews the mechanisms of action and pharmacological properties of different antiplatelet drugs. It also summarizes key trials that have evaluated antiplatelet therapies and provides recommendations from guidelines on treatment selection and duration based on a patient's risk of bleeding and thrombosis.
The EMPA-KIDNEY trial aims to evaluate whether empagliflozin can benefit patients with chronic kidney disease (CKD) and cardiovascular disease outcomes in patients with or without diabetes. The trial plans to enroll approximately 6,000 patients with CKD at risk of kidney disease progression, defined as an eGFR of 20-45 mL/min/1.73 m2 or an eGFR of 45-90 mL/min/1.73 m2 with albuminuria above 200 mg/g. Patients will be randomly assigned to receive empagliflozin 10 mg daily or placebo daily in addition to standard of care. The primary outcome is a composite of cardiovascular death, end-stage kidney disease,
1) Bifurcation stenting approaches are based on the angiographic configuration of lesions in the main and side branches. Significant disease (>50% stenosis) in the side branch ostium increases the risk of side branch closure and restenosis.
2) The default approach is one-stent with provisional side branch treatment. Two-stent techniques are used if the side branch has significant disease and high closure risk features.
3) Techniques like crush, culotte, and T-stenting aim to provide full coverage of both branches, but have limitations and risks. Physiologic assessment with IVUS and FFR can help decide if jailed side branches require intervention.
This document discusses SGLT2 inhibitors and DPP-4 inhibitors for the treatment of type 2 diabetes. SGLT2 inhibitors work by increasing glucose excretion in the urine, independently of insulin. They modestly lower blood pressure and weight. DPP-4 inhibitors work by inhibiting the DPP-4 enzyme and increasing GLP-1 and GIP levels. Both classes have few hypoglycemia risks but SGLT2 inhibitors should be used with caution in those with kidney impairment. Empagliflozin and canagliflozin are recommended for patients with cardiovascular disease.
Cardiovascular safety of anti-diabetic drugs.Cardiovascular Outcome Trials ...magdy elmasry
Cardiologists and diabetes.Target organs and action mechanism of antidiabetic drugs.Cardiovascular Outcome Trials
( CVOTs ) in Diabetes.Completed and ongoing CVOTs in type 2 diabetes.Diabetes Medications
and
Cardiovascular Impact.Recommendations for management of diabetes
Cardiovascular safety of anti-diabetic drugs.
Review of the New ACC/AHA Cholesterol GuidelinesTerry Shaneyfelt
The ACC/AHA recently released updated cholesterol treatment guidelines. I review them along with what I feel are their limitations. Watch my YouTube video describing these slides: http://youtu.be/2BlUhW6Zu2E
1) The IMPROVE-IT trial investigated whether adding ezetimibe to simvastatin therapy provides additional cardiovascular benefit compared to simvastatin monotherapy in 18,144 high-risk patients who recently had an acute coronary syndrome.
2) Patients receiving ezetimibe/simvastatin had a lower rate of major cardiovascular events (32.7% vs 34.7%) over a median follow-up of 6 years, demonstrating the additional clinical benefit of further lowering LDL-C with ezetimibe.
3) Ezetimibe/simvastatin also reduced the rate of the composite endpoint of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke compared to
What’s new in Lipidology, Lessons from “recent guidelines“Arindam Pande
1. The 2018 ACC/AHA cholesterol guidelines provide 10 key take-home messages focusing on lifestyle management, statin therapy for various risk groups, and risk assessment approaches.
2. The guidelines emphasize lifestyle therapy and statins for secondary prevention, with an LDL-C goal of 70 mg/dL for very high risk patients to consider adding nonstatins.
3. They provide guidance on statin use for various primary prevention groups based on risk levels and discussion, including an expanded definition of intermediate risk factors.
PCSK9 inhibitors are a new class of drugs for lowering LDL cholesterol by inhibiting the PCSK9 protein. They have been shown to reduce LDL levels by 40-72% as monotherapy or in combination with statins. While clinical trials have demonstrated excellent safety and efficacy, their high cost remains a limitation. Current guidelines recommend PCSK9 inhibitors as a second-line option for patients who cannot reach LDL goals despite maximal statin therapy or who are statin intolerant.
Central role of adenosine diphosphate P2Y12 receptor interaction in platelet activation and aggregation during occurrence of ischemic events and stent thrombosis. Clopidogrel is a pro-drug that requires conversion to its active metabolite by CYP450 enzymes, primarily CYP2C19, to irreversibly inhibit the P2Y12 receptor. There is significant variability in individual response to clopidogrel, with resistance reported in 4-44% of patients, due to factors such as CYP2C19 polymorphisms, drug-drug interactions, and clinical factors like diabetes. Both high and low levels of on-treatment platelet reactivity to ADP as measured by various assays have been associated with increased risks
Hypertension is a major concern & dreaded complication. It is known as the silent killer and responsible for a large number of cardiovascular morbidity and mortality. There are many antihypertensive drugs . Calcium channel blockers were the oldest one and widely used in the management. Azeldipine is the recent addition to this.
The CREDENCE trial evaluated the effect of canagliflozin vs placebo on renal outcomes in patients with type 2 diabetes and chronic kidney disease. Over 2.6 years of follow up:
1) Canagliflozin reduced the composite outcome of end-stage kidney disease, doubling of serum creatinine, and renal or cardiovascular death by 30% compared to placebo.
2) Canagliflozin also reduced cardiovascular death, myocardial infarction, stroke or hospitalization for heart failure by 30% compared to placebo.
3) The trial demonstrated that canagliflozin provided renoprotective and cardiovascular benefits in patients with type 2 diabetes and chronic kidney disease.
Cilnidipine is a dual-acting calcium channel blocker that blocks both L-type and N-type calcium channels. It is used to treat hypertension. Studies have shown that cilnidipine is as effective at lowering blood pressure as amlodipine, but it does not cause reflex tachycardia and has a lower risk of side effects like ankle edema. Combining cilnidipine with drugs that inhibit the renin-angiotensin-aldosterone system provides improved blood pressure control and reduces cardiac remodeling compared to other calcium channel blockers. Cilnidipine's unique dual blocking properties also help regulate leptin secretion, reducing atherosclerosis risk in obese hypertensive patients
Ranolazine is a second-line antianginal drug that inhibits late inward sodium currents, reducing calcium overload and improving myocardial perfusion. It has shown efficacy in reducing angina in clinical trials. Ranolazine also partially inhibits fatty acid oxidation, shifting metabolism from fatty acids to glucose. Common side effects include dizziness and constipation. It has potential utility for various conditions including microvascular coronary disease and post-operative atrial fibrillation, though evidence is limited for others such as acute coronary syndrome.
Association and prevalence of different comorbidities in hypertension and management with focus guidelines with benefits & choice of different antihypertensives in different comorbidities.
This document discusses the challenges of managing diabetes in patients with chronic kidney disease (CKD). It notes that diabetes is a leading cause of CKD progression and that CKD increases mortality risk in diabetes patients. Managing glucose levels in CKD patients is difficult due to risks of hypoglycemia from insulin clearance issues and need to adjust oral medications for kidney function. The CARMELINA trial demonstrated the renal safety of the DPP-4 inhibitor linagliptin in high cardio-renal risk patients, showing no increase in sustained decrease in eGFR or other renal outcomes compared to placebo over 2 years.
The document describes various hemodynamic measurements and pressure tracings obtained from right heart catheterization. It discusses normal and abnormal left ventricular pressure tracings and their components during systole and diastole. It also describes normal and abnormal right atrial, right ventricular, pulmonary artery, and pulmonary capillary wedge pressure tracings, including how different disease states can affect the pressure waveform morphology. Various concepts in hemodynamic measurements are summarized such as timing of pressure waves, effects of respiration, and identifying features of common cardiac pathologies.
This document summarizes several studies on the use of ACE inhibitors and angiotensin receptor blockers (ARBs) in treating heart failure and reducing cardiovascular risk. The HOPE trial showed that the ACE inhibitor ramipril reduced cardiovascular events in high-risk patients. The CHARM trial found that the ARB candesartan reduced cardiovascular outcomes in heart failure patients, both alone and in combination with ACE inhibitors. The ONTARGET trial aimed to compare the ARB telmisartan to ramipril, and their combination, to determine if telmisartan was non-inferior to ramipril and if their combination provided additional benefit.
This document summarizes information about diabetic dyslipidemia and the drug LIPAGLYN (Saroglitazar) as a novel treatment. It discusses that diabetic dyslipidemia involves high triglycerides, low HDL, and postprandial lipemia and increases cardiovascular and microvascular complications risk. Current treatments only partially address residual risk, so a dual PPAR-α/γ agonist is needed. Clinical trials found that LIPAGLYN reduced triglycerides and other lipid markers without weight gain or liver/kidney side effects compared to Pioglitazone. It concluded that LIPAGLYN is the best available option to target diabetic dyslipidemia along with stat
Javed Butler, MD, MPH, MBA, discusses heart failure in this CME activity titled, "New Frontiers in Managing Heart Failure: Are SGLT2 Inhibitors the Next Leap Forward in Optimizing Patient Care?" For the full presentation, downloadable infographics, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2JG2v9l. CME credit will be available until May 29, 2020.
LEQVIO (Inclisiran) is a small interfering RNA that inhibits PCSK9, which normally breaks down LDL receptors in the liver, leading to increased LDL cholesterol levels. Inclisiran is administered as two initial doses within 3 months, followed by twice yearly doses, to lower LDL cholesterol in adults with atherosclerotic cardiovascular disease who are already taking statins. By silencing the PCSK9 gene, inclisiran prevents PCSK9 from reducing LDL receptors on liver cells, allowing more LDL cholesterol to be removed from the bloodstream. Clinical trials showed inclisiran reduced LDL cholesterol by 50% compared to placebo when added to statin therapy.
1. Resistant Hypertension, complications, Target organ damage2. newly diagnosed stage-1 hypertension, rationale of use of ARB and comparison of Azilsartan with other ARBs3. Hypertension with bronchial asthma 4. Hypertension with Diabetes Mellitus with proteinuria5. Hypertension , Diabetes and IHD6. Gestational Hypertension , rationale of use of drugs7. Hypertension , Diabetes , ACS8. Hypertension, Diabetes and Syndrome X9. Hypertension and special situations
Amgen Cowen and Company 37th Annual Health Care Conference PresentationThe ScientifiK
This document summarizes an oral presentation given by David Meline, Executive Vice President and Chief Financial Officer of Amgen, at the Cowen and Company 37th Annual Health Care Conference on March 8, 2017. The presentation discusses Amgen's strong financial and operational execution in 2016, advancement of its innovative pipeline including positive cardiovascular outcomes data for Repatha, and growth opportunities across therapeutic areas like oncology, neuroscience, and bone health. It also reviews Amgen's biosimilars portfolio and strategy to invest in external innovation and deliver significant returns to shareholders through dividends and share repurchases.
Astrazeneca Full year and_q4_2016_results_presentationThe ScientifiK
The document provides an overview of AstraZeneca's full-year and Q4 2016 results presentation. It notes that total revenue was primarily impacted by generic competition for Crestor and the tail-end of Nexium's loss of exclusivity in the US. The "New AstraZeneca" grew by 6% in FY 2016 and Q4, led by growth in Emerging Markets, Symbicort, and Farxiga. EPS was supported by cost management. 2017 guidance forecasts low-to-mid single digit revenue decline and low-to-mid teens decline in core EPS. The presentation highlights pipeline progress including regulatory filings for Tagrisso, Durvalumab and Faslodex.
This document discusses SGLT2 inhibitors and DPP-4 inhibitors for the treatment of type 2 diabetes. SGLT2 inhibitors work by increasing glucose excretion in the urine, independently of insulin. They modestly lower blood pressure and weight. DPP-4 inhibitors work by inhibiting the DPP-4 enzyme and increasing GLP-1 and GIP levels. Both classes have few hypoglycemia risks but SGLT2 inhibitors should be used with caution in those with kidney impairment. Empagliflozin and canagliflozin are recommended for patients with cardiovascular disease.
Cardiovascular safety of anti-diabetic drugs.Cardiovascular Outcome Trials ...magdy elmasry
Cardiologists and diabetes.Target organs and action mechanism of antidiabetic drugs.Cardiovascular Outcome Trials
( CVOTs ) in Diabetes.Completed and ongoing CVOTs in type 2 diabetes.Diabetes Medications
and
Cardiovascular Impact.Recommendations for management of diabetes
Cardiovascular safety of anti-diabetic drugs.
Review of the New ACC/AHA Cholesterol GuidelinesTerry Shaneyfelt
The ACC/AHA recently released updated cholesterol treatment guidelines. I review them along with what I feel are their limitations. Watch my YouTube video describing these slides: http://youtu.be/2BlUhW6Zu2E
1) The IMPROVE-IT trial investigated whether adding ezetimibe to simvastatin therapy provides additional cardiovascular benefit compared to simvastatin monotherapy in 18,144 high-risk patients who recently had an acute coronary syndrome.
2) Patients receiving ezetimibe/simvastatin had a lower rate of major cardiovascular events (32.7% vs 34.7%) over a median follow-up of 6 years, demonstrating the additional clinical benefit of further lowering LDL-C with ezetimibe.
3) Ezetimibe/simvastatin also reduced the rate of the composite endpoint of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke compared to
What’s new in Lipidology, Lessons from “recent guidelines“Arindam Pande
1. The 2018 ACC/AHA cholesterol guidelines provide 10 key take-home messages focusing on lifestyle management, statin therapy for various risk groups, and risk assessment approaches.
2. The guidelines emphasize lifestyle therapy and statins for secondary prevention, with an LDL-C goal of 70 mg/dL for very high risk patients to consider adding nonstatins.
3. They provide guidance on statin use for various primary prevention groups based on risk levels and discussion, including an expanded definition of intermediate risk factors.
PCSK9 inhibitors are a new class of drugs for lowering LDL cholesterol by inhibiting the PCSK9 protein. They have been shown to reduce LDL levels by 40-72% as monotherapy or in combination with statins. While clinical trials have demonstrated excellent safety and efficacy, their high cost remains a limitation. Current guidelines recommend PCSK9 inhibitors as a second-line option for patients who cannot reach LDL goals despite maximal statin therapy or who are statin intolerant.
Central role of adenosine diphosphate P2Y12 receptor interaction in platelet activation and aggregation during occurrence of ischemic events and stent thrombosis. Clopidogrel is a pro-drug that requires conversion to its active metabolite by CYP450 enzymes, primarily CYP2C19, to irreversibly inhibit the P2Y12 receptor. There is significant variability in individual response to clopidogrel, with resistance reported in 4-44% of patients, due to factors such as CYP2C19 polymorphisms, drug-drug interactions, and clinical factors like diabetes. Both high and low levels of on-treatment platelet reactivity to ADP as measured by various assays have been associated with increased risks
Hypertension is a major concern & dreaded complication. It is known as the silent killer and responsible for a large number of cardiovascular morbidity and mortality. There are many antihypertensive drugs . Calcium channel blockers were the oldest one and widely used in the management. Azeldipine is the recent addition to this.
The CREDENCE trial evaluated the effect of canagliflozin vs placebo on renal outcomes in patients with type 2 diabetes and chronic kidney disease. Over 2.6 years of follow up:
1) Canagliflozin reduced the composite outcome of end-stage kidney disease, doubling of serum creatinine, and renal or cardiovascular death by 30% compared to placebo.
2) Canagliflozin also reduced cardiovascular death, myocardial infarction, stroke or hospitalization for heart failure by 30% compared to placebo.
3) The trial demonstrated that canagliflozin provided renoprotective and cardiovascular benefits in patients with type 2 diabetes and chronic kidney disease.
Cilnidipine is a dual-acting calcium channel blocker that blocks both L-type and N-type calcium channels. It is used to treat hypertension. Studies have shown that cilnidipine is as effective at lowering blood pressure as amlodipine, but it does not cause reflex tachycardia and has a lower risk of side effects like ankle edema. Combining cilnidipine with drugs that inhibit the renin-angiotensin-aldosterone system provides improved blood pressure control and reduces cardiac remodeling compared to other calcium channel blockers. Cilnidipine's unique dual blocking properties also help regulate leptin secretion, reducing atherosclerosis risk in obese hypertensive patients
Ranolazine is a second-line antianginal drug that inhibits late inward sodium currents, reducing calcium overload and improving myocardial perfusion. It has shown efficacy in reducing angina in clinical trials. Ranolazine also partially inhibits fatty acid oxidation, shifting metabolism from fatty acids to glucose. Common side effects include dizziness and constipation. It has potential utility for various conditions including microvascular coronary disease and post-operative atrial fibrillation, though evidence is limited for others such as acute coronary syndrome.
Association and prevalence of different comorbidities in hypertension and management with focus guidelines with benefits & choice of different antihypertensives in different comorbidities.
This document discusses the challenges of managing diabetes in patients with chronic kidney disease (CKD). It notes that diabetes is a leading cause of CKD progression and that CKD increases mortality risk in diabetes patients. Managing glucose levels in CKD patients is difficult due to risks of hypoglycemia from insulin clearance issues and need to adjust oral medications for kidney function. The CARMELINA trial demonstrated the renal safety of the DPP-4 inhibitor linagliptin in high cardio-renal risk patients, showing no increase in sustained decrease in eGFR or other renal outcomes compared to placebo over 2 years.
The document describes various hemodynamic measurements and pressure tracings obtained from right heart catheterization. It discusses normal and abnormal left ventricular pressure tracings and their components during systole and diastole. It also describes normal and abnormal right atrial, right ventricular, pulmonary artery, and pulmonary capillary wedge pressure tracings, including how different disease states can affect the pressure waveform morphology. Various concepts in hemodynamic measurements are summarized such as timing of pressure waves, effects of respiration, and identifying features of common cardiac pathologies.
This document summarizes several studies on the use of ACE inhibitors and angiotensin receptor blockers (ARBs) in treating heart failure and reducing cardiovascular risk. The HOPE trial showed that the ACE inhibitor ramipril reduced cardiovascular events in high-risk patients. The CHARM trial found that the ARB candesartan reduced cardiovascular outcomes in heart failure patients, both alone and in combination with ACE inhibitors. The ONTARGET trial aimed to compare the ARB telmisartan to ramipril, and their combination, to determine if telmisartan was non-inferior to ramipril and if their combination provided additional benefit.
This document summarizes information about diabetic dyslipidemia and the drug LIPAGLYN (Saroglitazar) as a novel treatment. It discusses that diabetic dyslipidemia involves high triglycerides, low HDL, and postprandial lipemia and increases cardiovascular and microvascular complications risk. Current treatments only partially address residual risk, so a dual PPAR-α/γ agonist is needed. Clinical trials found that LIPAGLYN reduced triglycerides and other lipid markers without weight gain or liver/kidney side effects compared to Pioglitazone. It concluded that LIPAGLYN is the best available option to target diabetic dyslipidemia along with stat
Javed Butler, MD, MPH, MBA, discusses heart failure in this CME activity titled, "New Frontiers in Managing Heart Failure: Are SGLT2 Inhibitors the Next Leap Forward in Optimizing Patient Care?" For the full presentation, downloadable infographics, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2JG2v9l. CME credit will be available until May 29, 2020.
LEQVIO (Inclisiran) is a small interfering RNA that inhibits PCSK9, which normally breaks down LDL receptors in the liver, leading to increased LDL cholesterol levels. Inclisiran is administered as two initial doses within 3 months, followed by twice yearly doses, to lower LDL cholesterol in adults with atherosclerotic cardiovascular disease who are already taking statins. By silencing the PCSK9 gene, inclisiran prevents PCSK9 from reducing LDL receptors on liver cells, allowing more LDL cholesterol to be removed from the bloodstream. Clinical trials showed inclisiran reduced LDL cholesterol by 50% compared to placebo when added to statin therapy.
1. Resistant Hypertension, complications, Target organ damage2. newly diagnosed stage-1 hypertension, rationale of use of ARB and comparison of Azilsartan with other ARBs3. Hypertension with bronchial asthma 4. Hypertension with Diabetes Mellitus with proteinuria5. Hypertension , Diabetes and IHD6. Gestational Hypertension , rationale of use of drugs7. Hypertension , Diabetes , ACS8. Hypertension, Diabetes and Syndrome X9. Hypertension and special situations
Amgen Cowen and Company 37th Annual Health Care Conference PresentationThe ScientifiK
This document summarizes an oral presentation given by David Meline, Executive Vice President and Chief Financial Officer of Amgen, at the Cowen and Company 37th Annual Health Care Conference on March 8, 2017. The presentation discusses Amgen's strong financial and operational execution in 2016, advancement of its innovative pipeline including positive cardiovascular outcomes data for Repatha, and growth opportunities across therapeutic areas like oncology, neuroscience, and bone health. It also reviews Amgen's biosimilars portfolio and strategy to invest in external innovation and deliver significant returns to shareholders through dividends and share repurchases.
Astrazeneca Full year and_q4_2016_results_presentationThe ScientifiK
The document provides an overview of AstraZeneca's full-year and Q4 2016 results presentation. It notes that total revenue was primarily impacted by generic competition for Crestor and the tail-end of Nexium's loss of exclusivity in the US. The "New AstraZeneca" grew by 6% in FY 2016 and Q4, led by growth in Emerging Markets, Symbicort, and Farxiga. EPS was supported by cost management. 2017 guidance forecasts low-to-mid single digit revenue decline and low-to-mid teens decline in core EPS. The presentation highlights pipeline progress including regulatory filings for Tagrisso, Durvalumab and Faslodex.
This document discusses Ruthigen, Inc., a drug development company focused on developing RUT58-60, a hypochlorous acid-based drug candidate for invasive use. RUT58-60 aims to improve patient outcomes for invasive procedures by reducing post-surgical infections in a more effective way than current standard of care antibiotics. Published studies on Microcyn, another hypochlorous acid-based product, show promise in reducing infection rates for diabetic foot ulcers and coronary artery bypass graft surgery wounds. If successful, RUT58-60 could help hospitals reduce costs by shortening patient stays and lowering readmission rates for post-surgical infections.
1) The ODYSSEY OUTCOMES trial evaluated long-term cardiovascular outcomes in patients with a history of acute coronary syndrome (ACS) who were treated with alirocumab (Praluent) or placebo while receiving statin therapy.
2) The trial found that alirocumab reduced the risk of the primary composite endpoint of cardiovascular death, non-fatal myocardial infarction, ischemic stroke, or unstable angina requiring hospitalization compared to placebo.
3) Additionally, alirocumab was associated with a lower rate of all-cause mortality compared to placebo, representing the first time a non-statin lipid-lowering therapy has demonstrated a reduction in all-cause mortality in a cardiovascular outcomes trial
12 05 08 deutsche bank healthcare conference supporting materialsThe ScientifiK
Amgen provided an overview of its business and pipeline at the 37th Annual Health Care Conference on May 8, 2012. Key points included: Amgen started 2012 strongly with record revenues and earnings; growth drivers included Neulasta, Enbrel, XGEVA, and Prolia; the ESA business now represents a smaller proportion of sales; pipeline programs like AMG 145 and AMG 785 are advancing; and recent partnerships and acquisitions have enhanced the pipeline and international business. Amgen reiterated forward-looking statements are subject to risks and uncertainties that could cause actual results to differ from projections.
Webinar: Global Supply Chain Dynamics & The Changing Risk Management AgendaArt Stewart, MPM
This is the slide deck from the first of a two-part Webinar produced and moderated by Art Stewart in partnership with the Corporate Responsibility Association. It covers: Innovations in global supply chain management that are transforming the traditional sourcing paradigm; specific developments in key industries that are impacting supply chain dynamics; new opportunities for CR professionals to extend their C-suite influence via supply chain and risk matters; and a CR check list of strategies and tactics for mitigating emerging supply chain issues. Part II will be Wednesday, February 11, 2015 at 12 Noon EST.
Impax reported its fourth quarter and full year 2016 financial results. Revenue declined year-over-year due to continued pricing pressures and volatility in the generic drug market. The company reported a net loss for the year due to non-cash impairment charges related to intangible assets. Looking ahead, Impax expects the challenging market conditions to continue but believes its specialty drug portfolio and generic pipeline can drive growth. Key priorities for 2017 include reducing debt, improving efficiency, and investing in R&D and generic launches.
- The document presents information on Praluent (alirocumab), the first PCSK9 inhibitor therapy approved in the US for treatment of adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease who require additional lowering of LDL cholesterol.
- Praluent demonstrated robust and durable LDL-C reduction of over 52 weeks in clinical trials in patients on maximally tolerated statin therapy, with 57-83% of patients achieving sufficient LDL-C reduction with the 75 mg starting dose.
- The Committee for Medicinal Products for Human Use adopted a positive opinion for Praluent in Europe, and approval is expected in late September 2015. The OD
The document discusses Sanofi and Regeneron's Phase 3 clinical trial program for sarilumab, an investigational IL-6 receptor monoclonal antibody for the treatment of rheumatoid arthritis. The program includes several trials involving over 5,000 patients total to evaluate sarilumab both as monotherapy and in combination with methotrexate or other disease-modifying anti-rheumatic drugs. The two largest trials, MOBILITY and TARGET, enrolled over 1,700 patients and evaluated sarilumab versus placebo for improving signs and symptoms of rheumatoid arthritis and physical function when added to background therapy. Results from these trials demonstrated statistically significant improvements for sarilumab compared to placebo.
Interpace Diagnostics provides molecular diagnostic tests and pathology services to evaluate cancer risk. The presentation discusses:
1) Interpace's product portfolio including tests that risk-stratify pancreatic cysts, Barrett's esophagus, and thyroid nodules.
2) Clinical evidence and guidelines supporting their tests, and growth in adoption and coverage by payers.
3) Financial highlights including recent funding raises, revenue growth, and progress reducing costs.
4) Drivers for continued growth including expanding sales force and strategic partnerships.
Virios Therapeutics is a clinical-stage biotechnology company focused on advancing novel, dual mechanism antiviral therapies to treat conditions associated with virally triggered or maintained immune responses, such as Fibromyalgia (“FM”). Immune responses related to the activation of tissue resident Herpes Simplex Virus-1 (“HSV-1”) have been postulated as a potential root cause triggering and/or sustaining chronic illnesses such as FM, irritable bowel disease (“IBS”), and chronic fatigue syndrome, all of which can be characterized by waxing and waning symptom flare-ups with no obvious etiology. Virios’ lead development candidate (“IMC-1”) is a novel, proprietary, fixed dose combination of famciclovir and celecoxib designed to synergistically suppress HSV-1 replication, with the end goal of reducing virally promoted disease symptoms.
Udit Batra, CEO of Life Science at Merck KGaA, presented at the UBS Global Healthcare Conference in New York on May 23, 2016. Merck KGaA is a leader in the life science industry with a portfolio of three high-tech businesses: Life Science, Performance Materials, and Healthcare. The integration of the Sigma-Aldrich acquisition is on track to deliver cost synergies while maintaining sales momentum in the Life Science business. Merck KGaA expects mid-single digit organic growth in Life Science in 2016, driven primarily by the Process Solutions business unit.
Virios Therapeutics is a clinical-stage biotechnology company focused on
advancing novel, dual mechanism antiviral therapies to treat conditions
associated with virally triggered or maintained immune responses, such as
Fibromyalgia (“FM”). Immune responses related to the activation of tissue
resident Herpes Simplex Virus-1 (“HSV-1”) have been postulated as a
potential root cause triggering and/or sustaining chronic illnesses such as
FM, irritable bowel disease (“IBS”), and chronic fatigue syndrome, all of
which can be characterized by waxing and waning symptom “flair-ups” with
no obvious etiology. Virios’ lead development candidate (“IMC-1”) is a
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2. 2
Provided March 17, 2017, as part of an oral presentation and is qualified by
such, contains forward-looking statements, actual results may vary
materially; Amgen disclaims any duty to update.
SAFE HARBOR STATEMENT
This presentation contains forward-looking statements that are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and
assumptions that could cause actual results to differ materially from those described. All statements, other than statements of historical fact, are statements that could be deemed
forward-looking statements, including statements about 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 (SEC)
reports filed by Amgen, including Amgen’s most recent annual report on Form 10-K and any subsequent periodic reports on Form 10-Q and Form 8-K. Please refer to Amgen’s most
recent Forms 10-K, 10-Q and 8-K for additional information on the uncertainties and risk factors related to our business. Unless otherwise noted, Amgen is providing this information
as of March 17, 2017 and expressly disclaims any duty to update information contained in this presentation.
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,
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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
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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
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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.
This presentation includes GAAP and non-GAAP financial measures. In accordance with the requirements of SEC Regulation G, reconciliations between these two measures, if these
slides are in hard copy, accompany the hard copy presentation or, if these slides are delivered electronically, are available on the Company's website at www.amgen.com within the
Investors section.
3. 3
Provided March 17, 2017, as part of an oral presentation and is qualified by
such, contains forward-looking statements, actual results may vary
materially; Amgen disclaims any duty to update.
AGENDA
Introduction
Sean Harper, M.D.—Executive Vice President, Research
and Development
Repatha® Phase 3
CV Outcomes Study
Marc Sabatine, M.D., M.P.H.—Chairman of the TIMI Study Group,
Brigham and Women’s Hospital, Harvard Medical School
Repatha® Value
Joshua Ofman, M.D.—Senior Vice President, Global Value, Access
and Policy
Conclusion Sean Harper, M.D.
Q&A
Sean Harper, M.D.
Joshua Ofman, M.D.
Marc Sabatine, M.D., M.P.H.
Tony Hooper—Executive Vice President, Global Commercial Operations
Scott Wasserman, M.D.—Vice President, Research and Development
Terje R. Pedersen, M.D., Ph.D.—Oslo University Hospital, Ullevål
CV = cardiovascular
7. An Academic Research Organization of
Brigham and Women’s Hospital and Harvard Medical School
FOURIER
Further cardiovascular OUtcomes
Research with PCSK9 Inhibition in
subjects with Elevated Risk
MS Sabatine, RP Giugliano, AC Keech, N Honarpour,
SM Wasserman, PS Sever, and TR Pedersen,
for the FOURIER Steering Committee & Investigators
American College of Cardiology – 66th Annual Scientific Session
Late-Breaking Clinical Trial
March 17, 2017
8. An Academic Research Organization of
Brigham and Women’s Hospital and Harvard Medical School
Sever P & Mackay J. Br J Cardiol 2014;21:91-3
Giugliano RP, et al. Lancet 2012;380:2007-17
Sabatine MS, et al. NEJM 2015;372:1500-9
Proprotein convertase subtilisin/kexin type 9 (PCSK9)
– Chaperones LDL-R to destruction circulating LDL-C
– Loss-of-fxn genetic variants LDL-R LDL-C & risk of MI
Evolocumab
– Fully human anti-
PCSK9 mAb
– ~60% LDL-C
– Safe & well-tolerated in
Ph 2 & 3 studies
– Exploratory data
suggested CV events
Background
evolocumab
9. An Academic Research Organization of
Brigham and Women’s Hospital and Harvard Medical School
Objectives
In patients with established cardiovascular disease
on statin therapy:
• Test whether the addition of evolocumab reduces the
incidence of major cardiovascular events
• Examine the long-term safety & tolerability of
evolocumab
• Investigate the efficacy and safety of achieving
unprecedented low levels of LDL-C
10. An Academic Research Organization of
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Trial Organization
Executive Committee
Marc S. Sabatine (Co-Chair) Terje R. Pedersen (Co-Chair)
Robert P. Giugliano Anthony C. Keech Peter S. Sever
TIMI Study Group
Stephen D. Wiviott (CEC Chair) Cheryl Lowe Leah Zahn
Marc P. Bonaca (Safety Chair) Polly Fish (Director of Ops) Tim Abrahamsen
Sabina Murphy (Director of Stats) Kelly Im (Assoc Dir Stats) Julia Kuder
Estella Kanevsky
Sponsor: Amgen
Scott M. Wasserman Narimon Honarpour Rob Scott
Armando Lira Pineda Kelly Hanlon Beat Knusel
Ransi Somaratne Christopher Kurtz Thomas Liu
Huei Wang
Independent Data Monitoring Committee
Charles H. Hennekens (Chair) Felicita Andreotti Colin Baigent
W. Virgil Brown Barry R. Davis
John W. Newcomer
Sarah K. Wood
Lipid Monitoring Committee
John LaRosa (Chair) Benjamin Ansell Anders Olsson
11. An Academic Research Organization of
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Trial Design
Evolocumab SC
140 mg Q2W or 420 mg QM
Placebo SC
Q2W or QM
LDL-C ≥70 mg/dL or
non-HDL-C ≥100 mg/dL
Follow-up Q 12 weeks
Screening, Lipid Stabilization, and Placebo Run-in
High or moderate intensity statin therapy (± ezetimibe)
27,564 high-risk, stable patients with established CV disease
(prior MI, prior stroke, or symptomatic PAD)
RANDOMIZED
DOUBLE BLIND
Sabatine MS et al. Am Heart J 2016;173:94-101
12. An Academic Research Organization of
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Endpoints
• Efficacy
– Primary: CV death, MI, stroke, hosp. for UA, or coronary revasc
– Key secondary: CV death, MI or stroke
• Safety
– AEs/SAEs
– Events of interest incl. muscle-related, new-onset diabetes,
neurocognitive
– Development of anti-evolocumab Ab (binding and neutralizing)
• TIMI Clinical Events Committee (CEC)
– Adjudicated all efficacy endpoints & new-onset diabetes
– Members unaware of treatment assignment & lipid levels
Sabatine MS et al. Am Heart J 2016;173:94-101
13. An Academic Research Organization of
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Argentina Estonia Japan Singapore
Alberto J. Lorenzatti Margus Viigimaa Atsushi Hirayama Leslie Tay
Australia Finland Latvia Slovakia
John Amerena Matti J. Tikkanen Andrejs Erglis Slavomíra Filipová
Austria France Lithuania South Africa
Kurt Huber François Schiele Jolita Badariene Lesley Burgess
Belgium Germany Malaysia South Korea
André Scheen Ioanna Gouni-Berthold Wan A. Wan Ahmad Donghoon Choi
Brazil Greece Mexico Spain
José F.K. Saraiva Loukianos Rallidis G. Gonzalez-Galvez José López-Miranda
Bulgaria Hong Kong Netherlands Sweden
Borislav G. Georgiev Chung-Wah Siu J. Wouter Jukema Lennart Nilsson
Canada Hungary Norway Switzerland
Lawrence A. Leiter Kalman Toth Terje R. Pedersen François Mach
Chile Iceland Philippines Taiwan
Jorge L. Cobos Gudmundur Thorgeirsson Gregorio G. Rogelio Min-Ji Charng
China India Poland Turkey
Lixin Jiang P. Deedwania & V. Chopra Zbigniew A. Gaciong S. Lale Tokgozoglu
Colombia Ireland Portugal Ukraine
Jose L.A. Mendoza Brendan McAdam Jorge Ferreira Oleg Kraydashenko
Czech Republic Israel Romania United Kingdom
Richard Ceska Basil S. Lewis Gheorghe A. Dan Peter S. Sever
Denmark Italy Russia United States
Henrik K. Jensen Gaetano M. De Ferrari Marat V. Ezhov Robert P. Giugliano
Steering Committee
14. An Academic Research Organization of
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27,564 patients randomized at 1242 sites
in 49 countries between 2/2013 – 6/2015
Global Enrollment
15. An Academic Research Organization of
Brigham and Women’s Hospital and Harvard Medical School
Randomized 27,564 patients
Evolocumab
(N=13,784)
Placebo
(N=13,780)
Premature perm.
drug discontinuation
5.6%/yr 5.8%/yr
Withdrew consent 0.29%/yr 0.35%/yr
Lost to follow-up 5 patients 13 patients
Follow-up median 26 months (IQR 22-30)
Ascertainment for primary endpoint was complete for
99.5% of potential patient-years of follow up
Follow-up
2907 patients experienced primary
endpoint
1829 experienced key secondary endpoint
16. An Academic Research Organization of
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Baseline Characteristics
Characteristic Value
Age, years, mean (SD) 63 (9)
Male sex (%) 75
Type of cardiovascular disease (%)
Myocardial infarction 81
Stroke (non-hemorrhagic) 19
Symptomatic PAD 13
Cardiovascular risk factor (%)
Hypertension 80
Diabetes mellitus 37
Current cigarette use 28
Pooled data; no differences between treatment arms
Median time from most
recent event ~3 yrs
17. An Academic Research Organization of
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Baseline CV Meds
Characteristic Value
ASA and/or P2Y12 Inhibitor (%) 92
Beta-blocker (%) 76
ACE inhibitor or ARB and/or
aldosterone antagonist (%)
78
18. An Academic Research Organization of
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Lipid Lowering Therapy
& Lipid Levels at Baseline
Characteristic Value
Statin use (%)*
High-intensity 69
Moderate-intensity 30
Ezetimibe use (%) 5
Median lipid measures (IQR) – mg/dL
LDL-C 92 (80-109)
Total cholesterol 168 (151-189)
HDL-C 44 (37-53)
Triglycerides 133 (100-182)
Pooled data; no differences between treatment arms
*Per protocol, patients were to be on atorva ≥20 mg/d or equivalent.
1% were on low intensity or intensity data were missing.
Statin intensity defined per ACC/AHA 2013 Cholesterol Guidelines.
19. An Academic Research Organization of
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0
10
20
30
40
50
60
70
80
90
100
0 12 24 36 48 60 72 84 96 108120132144156168
LDLCholesterol(mg/dl)
Weeks
LDL Cholesterol
Evolocumab
(median 30 mg/dl, IQR 19-46 mg/dl)
Placebo
59% mean reduction (95%CI 58-60), P<0.00001
Absolute reduction: 56 mg/dl (95%CI 55-57)
20. An Academic Research Organization of
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0
10
20
30
40
50
60
70
80
90
100
0 12 24 36 48 60 72 84 96 108 120
LDLCholesterol(mg/dl)
Weeks
LDL Cholesterol
Cohort of 11,077 patients who
• had all measurements through 120 weeks
• did not discontinue study drug
• did not D concomitant background lipid-lowering Rx
Evolocumab
Placebo
Similar data out to 4 years
in OSLER-1
(JAMA Cardiology online)
21. An Academic Research Organization of
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0%
2%
4%
6%
8%
10%
12%
14%
16%
Primary Endpoint
Evolocumab
Placebo
Months from Randomization
CVDeath,MI,Stroke,
HospforUA,orCorRevasc
0 6 12 18 24 30 36
Hazard ratio 0.85
(95% CI, 0.79-0.92)
P<0.0001 12.6%
14.6%
22. An Academic Research Organization of
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0%
1%
2%
3%
4%
5%
6%
7%
8%
9%
10%
Key Secondary Endpoint
Months from Randomization
CVDeath,MI,orStroke
0 6 12 18 24 30 36
Hazard ratio 0.80
(95% CI, 0.73-0.88)
P<0.00001
Evolocumab
Placebo
7.9%
9.9%
23. An Academic Research Organization of
Brigham and Women’s Hospital and Harvard Medical School
Types of CV Outcomes
Endpoint
Evolocumab
(N=13,784)
Placebo
(N=13,780) HR (95% CI)
3-yr Kaplan-Meier rate
CV death, MI, or stroke 7.9 9.9 0.80 (0.73-0.88)
Cardiovascular death 2.5 2.4 1.05 (0.88-1.25)
Death due to acute MI 0.26 0.32 0.84 (0.49-1.42)
Death due to stroke 0.29 0.30 0.94 (0.58-1.54)
Other CV death 1.9 1.8 1.10 (0.90-1.35)
MI 4.4 6.3 0.73 (0.65-0.82)
Stroke 2.2 2.6 0.79 (0.66-0.95)
24. An Academic Research Organization of
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More Intensive LDL-C Lowering
& CV Death
# of CV Deaths
Trial Year More
Intensive
Rx Arm
Less
Intensive
Rx Arm
HR (95% CI)
PROVE-IT TIMI 22 2004 27 36 0.74 (0.45-1.22)
A2Z 2004 86 111 0.76 (0.57-1.01)
TNT 2005 101 127 0.80 (0.61-1.03)
IDEAL 2005 223 218 1.03 (0.85-1.24)
SEARCH 2010 565 572 0.99 (0.88-1.11)
IMPROVE-IT 2015 538 537 1.00 (0.89-1.13)
Summary 1540 1601 0.96 (0.90-1.03)
More intensive
therapy better
Less intensive
therapy better
0.2 0.5 1 2 5
NEJM 2004;350:1495-504
JAMA 2004;292:1307-16
NEJM 2005;352:1425-35
JAMA 2005;294:2437-45
Lancet 2010;376:1658-69
NEJM 2015;372:2387-97
No clear benefit on CV mortality
25. An Academic Research Organization of
Brigham and Women’s Hospital and Harvard Medical School
Types of CV Outcomes
Endpoint
Evolocumab
(N=13,784)
Placebo
(N=13,780) HR (95% CI)
3-yr Kaplan-Meier rate
CVD, MI, stroke, UA, or revasc 12.6 14.6 0.85 (0.79-0.92)
CV death, MI, or stroke 7.9 9.9 0.80 (0.73-0.88)
Cardiovascular death 2.5 2.4 1.05 (0.88-1.25)
MI 4.4 6.3 0.73 (0.65-0.82)
Stroke 2.2 2.6 0.79 (0.66-0.95)
Hosp for unstable angina 2.2 2.3 0.99 (0.82-1.18)
Coronary revasc 7.0 9.2 0.78 (0.71-0.86)
Urgent 3.7 5.4 0.73 (0.64-0.83)
Elective 3.9 4.6 0.83 (0.73-0.95)
Death from any cause 4.8 4.3 1.04 (0.91-1.19)
26. An Academic Research Organization of
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Key Subgroups
Subgroup Patients
Overall 27564
Type of disease
MI alone 19113
Stroke alone 3366
PAD alone 1505
Polyvascular disease 3563
Baseline LDL-C
Q1 (<80 mg/dl) 6961
Q2 (80-<92 mg/dl) 6886
Q3 (92-109 mg/dl) 6887
Q4 (>109 mg/dl) 6829
Baseline statin intensity
High 19103
Not high 8461
Ezetimibe
Yes 1440
No 26124
Initial Dosing Regimen
Every 2 weeks 24774
Monthly 2790
1° Endpoint HR (95% CI) Key 2° Endpoint HR (95% CI)
1.0
EvoMab better Pbo better
0.4 2.5 1.0
EvoMab better Pbo better
0.4 2.5
All Pinteractions NS
27. An Academic Research Organization of
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Lower LDL-C Is Better
P<0.0001
Patients divided by quartile of baseline LDL-C and by treatment arm
Q4
Q3
Q2
Q1
Q4
Q3
Q2
Q1
Placebo
Evolocumab
28. An Academic Research Organization of
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LDL-C & D in Plaque Volume
JAMA 2016;316:2373-84
29. An Academic Research Organization of
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0%
2%
4%
6%
8%
0%
2%
4%
6%
8%
Landmark Analysis
Evolocumab
Placebo
Months from Randomization
CVDeath,MI,Stroke
0 3 9 12 24 30 366 12 18
16% RRR
HR 0.84 (95%CI 0.74-0.96)
P=0.008
25% RRR
HR 0.75 (95%CI 0.66-0.85)
P<0.00001
30. An Academic Research Organization of
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0%
2%
4%
6%
8%
0%
2%
4%
6%
8%
Fatal or Nonfatal MI or Stroke
Evolocumab
Placebo
Months from Randomization
FatalorNonfatalMIorStroke
0 3 9 12 24 30 366 12 18
19% RRR
HR 0.81 (95%CI 0.70-0.93)
P=0.003
33% RRR
HR 0.67 (95%CI 0.59-0.77)
P<0.00001
31. An Academic Research Organization of
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Comparison to Cholesterol
Treatment Trialists Collaboration
Major Coronary Events
Stroke
Coronary revascularization
Major Vascular Events
0.78 (0.70-0.86)
0.77 (0.66-0.91)
0.75 (0.67-0.84)
0.77 (0.73-0.82)
Lipid-lowering therapy better Lipid-lowering therapy worse
Hazard Ratio (95% CI) per 1 mmol/L reduction in LDL-C
2.01.0
CTTC Meta-analysis Year 2
CTTC data from Lancet 2010;376:1670-81
0.5
32. An Academic Research Organization of
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Comparison to Cholesterol
Treatment Trialists Collaboration
Major Coronary Events
Stroke
Coronary revascularization
Urgent
Elective
Major Vascular Events
0.78 (0.70-0.86)
0.80 (0.71-0.90)
0.77 (0.66-0.91)
0.77 (0.63-0.94)
0.75 (0.67-0.84)
0.73 (0.62-0.86)
0.84 (0.73-0.98)
0.77 (0.73-0.82)
0.83 (0.76-0.90)
Lipid-lowering therapy better Lipid-lowering therapy worse
Hazard Ratio (95% CI) per 1 mmol/L reduction in LDL-C
2.01.0
CTTC Meta-analysis Year 2
FOURIER Year 2
CTTC data from Lancet 2010;376:1670-81
0.5
33. An Academic Research Organization of
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Safety
Evolocumab
(N=13,769)
Placebo
(N=13,756)
Adverse events (%)
Any 77.4 77.4
Serious 24.8 24.7
Allergic reaction 3.1 2.9
Injection-site reaction 2.1 1.6
Treatment-related and led to d/c of study drug 1.6 1.5
Muscle-related 5.0 4.8
Cataract 1.7 1.8
Diabetes (new-onset) 8.1 7.7
Neurocognitive 1.6 1.5
Laboratory results (%)
Binding Ab 0.3 n/a
Neutralizing Ab none n/a
New-onset diabetes assessed in patients without diabetes at baseline; adjudicated by CEC
34. An Academic Research Organization of
Brigham and Women’s Hospital and Harvard Medical School
Summary for Evolocumab
• LDL-C by 59%
– Consistent throughout duration of trial
– Median achieved LDL-C of 30 mg/dl (IQR 19-46 mg/dl)
• CV outcomes in patients already on statin therapy
– 15% broad primary endpoint; 20% CV death, MI, or stroke
– Consistent benefit, incl. in those on high-intensity statin, low LDL-C
– 25% reduction in CV death, MI, or stroke after 1st year
– Long-term benefits consistent w/ statins per mmol/L LDL-C
• Safe and well-tolerated
– Similar rates of AEs, incl DM & neurocog events w/ EvoMab & pbo
– Rates of EvoMab discontinuation low and no greater than pbo
– No neutralizing antibodies developed
35. An Academic Research Organization of
Brigham and Women’s Hospital and Harvard Medical School
Conclusions
In patients with known cardiovascular disease:
1. PCSK9 inhibition with evolocumab
significantly & safely major cardiovascular
events when added to statin therapy
2. Benefit was achieved with lowering LDL
cholesterol well below current targets
36. An Academic Research Organization of
Brigham and Women’s Hospital and Harvard Medical School
Further Details
Article available at www.nejm.org
Slides available at www.TIMI.org
38. 38
Provided March 17, 2017, as part of an oral presentation and is qualified by
such, contains forward-looking statements, actual results may vary
materially; Amgen disclaims any duty to update.
IN CV DISEASE, ECONOMIC VALUE IS DRIVEN BY BASELINE
EVENT RATE AND TREATMENT EFFECTIVENESS
Efficacy
Baseline
Event
Rates
Direct
Medical
Costs
Drug
Costs
Quality
of Life
Treatment
Duration
Length
of Life
Indirect
Medical
Costs
39. 39
Provided March 17, 2017, as part of an oral presentation and is qualified by
such, contains forward-looking statements, actual results may vary
materially; Amgen disclaims any duty to update.
EVENT RATES BASED ON REAL-WORLD DATA ARE HIGHER
THAN EVENT RATES REPORTED IN CLINICAL TRIALS
4.5 5.2
9.8
12.3
0
2
4
6
8
10
12
14
EventRateper100
Patient-Years
Real-World
Data3
• CV events include MI, UA, IS, coronary revascularization (coronary artery bypass graft or percutaneous coronary intervention), or CV-related death
• Real-world event rates are based on an analysis of patients in the UK CPRD database between 2004 and 2011. Patients were included in the
analysis based on eligibility criteria for the Repatha® Outcomes Study—FOURIER3
CTTC1
Meta-Analysis
Repatha® Outcomes Trial2
First Event
All Events
First Event
All Events
MI = myocardial infarction; UA = unstable angina; IS = ischemic stroke; CPRD = Clinical Practice Research Datalink; 1. CTTC, et. al. Lancet 2010 376: 1670-1681; 2. Sabatine MS, et al . NEJM.
[published online ahead of print March 17, 2017]; 3.Toth PP, et al. J Med Econ. 2017. In Press
40. 40
Provided March 17, 2017, as part of an oral presentation and is qualified by
such, contains forward-looking statements, actual results may vary
materially; Amgen disclaims any duty to update.
Analyses using event
rates from trials
Analyses using real-
world event rates
BaselineEventRate(%)
1. Kazi DS, et al. JAMA. 2016;316(7):743-753. 2. Arrieta A, et al. PLoS One. 2017;12(1):e0169761. 3. Jena AB, et al. Am J Manag Care. 2016;22(6):e199-e207. 4. Gandra SR, et al. Clin Cardiol.
2016;39(6):313-320. 5. Toth PP, et al. J Med Econ. 2017. In Press. 6. Data on file, Amgen; [PHE Analysis; 2017]
Less Value More Value
USE OF REAL-WORLD EVENT RATE DATA TRANSLATES
INTO PCSK9 INHIBITOR REAL-WORLD ECONOMIC VALUE1-6
16
14
12
10
8
6
4
2
–
41. 41
Provided March 17, 2017, as part of an oral presentation and is qualified by
such, contains forward-looking statements, actual results may vary
materially; Amgen disclaims any duty to update.
Value-Based Price Range†
LDL > 70 = $7,700–$11,200
LDL > 100 = $10,400–$15,000
Economic analyses using
real-world event rates show
value-based price ranges
from $11,900–$17,000*
THE ECONOMIC VALUE OF REPATHA®
REPATHA® OUTCOMES TRIAL
• 20% RRR on hard MACE composite endpoint
• 25% RRR on hard MACE composite endpoint at > year 1
• 33% RRR on fatal and nonfatal MI or CVA at > 1 year
• Economic models typically include mortality benefit seen in CTTC
• Multiple alternative approaches employed using a 2-year time lag
RRR = relative risk reduction; MACE = major adverse cardiovascular event; CVA = cerebrovascular accident; CTTC = Cholesterol Treatment Trialists Collaboration; *Jena AB,
et al. Am J Manag Care. 2016;22(6):e199-e207. Gandra SR, et al. Clin Cardiol. 2016;39(6):313-320. Toth PP, et al. J Med Econ. 2017. In Press; †Willingness to pay of $150K/QALY
PRIOR PUBLICATIONS
42. 42
Provided March 17, 2017, as part of an oral presentation and is qualified by
such, contains forward-looking statements, actual results may vary
materially; Amgen disclaims any duty to update.
PRICES IN THE MARKET TODAY ARE WITHIN
THE VALUE-BASED PRICE RANGE
Current
Net Prices
$15,000
per year
Value-Based Price Range
LDL > 100
LDL > 70
$10,400
per year
$11,200
per year
$7,700
per year
43. 43
Provided March 17, 2017, as part of an oral presentation and is qualified by
such, contains forward-looking statements, actual results may vary
materially; Amgen disclaims any duty to update.
Current utilization management is preventing appropriate patients from
getting the right treatment, the lack of outcomes data has been a barrier
and this key objection can be taken off the table
The Repatha® Outcomes data provide added conviction that the
discounted prices in the U.S. market today are value based
Innovative contracts/financial risk-sharing agreements aimed at allowing
payers to fulfill their access obligations while providing budget
predictability as utilization increases
Amgen will offer contracting options to payers willing to remove access
barriers, including one option that offers a refund of the cost of Repatha®
for all of their eligible patients who have a heart attack or stroke
AMGEN IS COMMITTED TO HELPING PATIENTS GET ACCESS
TO REPATHA®
Compelling
Outcomes Data
Added Conviction
Innovative Risk-
Sharing Contracts
Outcomes-Based
Contracts
44. 44
Provided March 17, 2017, as part of an oral presentation and is qualified by
such, contains forward-looking statements, actual results may vary
materially; Amgen disclaims any duty to update.
VALUE-BASED
PRICING
Per-Member-
Per-Year
Threshold
Volume
Discounts
Outcome
Based
Refund
OR
LDL Contract
OR
Performance and
Outcomes Based
Contracts
CV Events
Contract
OR
Contracts Based
on Cost
Predictability
TO ADDRESS ACCESS RESTRICTIONS, AMGEN IS OFFERING INNOVATIVE RISK-SHARING
PERFORMANCE CONTRACTS TO ENGAGE PAYERS IN IMPROVING HEALTH OUTCOMES
These are innovative contract options that will be discussed with payers
45. 45
Provided March 17, 2017, as part of an oral presentation and is qualified by
such, contains forward-looking statements, actual results may vary
materially; Amgen disclaims any duty to update.
NUMBER NEEDED TO TREAT (NNT) DOES NOT DETERMINE
A MEDICINE’S VALUE
NNT is Not Recommended by Health Authorities*—
Is Rarely Used in Health Economics
NNT Counts Events, Not the Impact of Events
Well-Known Limitations in Health Economics
“QALYs are health economic measures
incorporating both benefits and harms of
each treatment outcome. In contrast, NNT
or NNH simply summarizes the proportion
of patients impacted positively or
negatively by the treatment”
“QALYs provide significantly more
information regarding the impact of
different outcomes that may result from
therapeutic alternatives rather than the few
outcomes addressed by NNT or NNH”
QALY = quality-adjusted life year; NNH = number needed to harm
*Sanders et al, JAMA. 2016; 316(10): 1093-1103
NNT Does Not Capture Important Elements of Value—
Quality of Life or Additional Years of Life
Garg et al, Annals of Pharmacotherapy. 2013;47(3):380-387
46. 46
Provided March 17, 2017, as part of an oral presentation and is qualified by
such, contains forward-looking statements, actual results may vary
materially; Amgen disclaims any duty to update.
PHYSICIAN ASSOCIATIONS AND PATIENT ORGANIZATIONS ARE
INCREASING THEIR ACTIVITIES ON ISSUES OF PATIENT ACCESS
American Medical Association 21 principles to reform prior-authorization requirements
American College of
Cardiology survey
Barriers to New Medications for Cardiovascular Disease
National Lipid Association survey Challenges in Prescribing PCSK9 Inhibitors
American Society for Preventive
Cardiology Town Hall meeting
Unraveling a Therapeutic Conundrum: A Town Hall on Barriers
to Access PCSK9
American Association of Clinical
Endocrinologists
New lipid guidelines published online January 30 with PCSK9s
second-line therapy after statins
FH Foundation
Implementing “Find FH” to improve diagnosis rates; gathering data
on treatment patterns; collaborating with Express Scripts to improve
pharmacy coverage for patients with FH
FH = familial hypercholesterolemia
48. 48
Provided March 17, 2017, as part of an oral presentation and is qualified by
such, contains forward-looking statements, actual results may vary
materially; Amgen disclaims any duty to update.
Primary Results of EBBINGHAUS, a Cognitive Study of Patients Enrolled
in the FOURIER Trial
Giugliano et. al. Abstract 404-16
Late-Breaking Clinical Trials, Saturday, March 18, 9–9:10 a.m. ET
Characteristics of Patients Approved and Denied Access
to PCSK9i Therapy by Payers
Baum et al. Abstract 1258-435
Innovations in Advocacy and Patient Centered Care, Saturday, March 18, 3:45–4:30 p.m. ET
Early Challenges for PCSK9 Inhibitor Prescriptions and Patients:
Rejections and Rates Unfilled
Navar et al. Abstract 415-08
Featured Clinical Research III, Sunday, March 19, 2–2:10 p.m. ET
Cardiac Myosin Activator, Omecamtiv Mecarbil, Improves Left Ventricular Myocardial
Deformation in Chronic Heart Failure (COSMIC-HF)
Biering-Sørensen et al. Abstract 1248-244
Heart Failure and Cardiomyopathies: What Next When All Else Is Failing?, Saturday, March 18, 3:45–4:30 p.m. ET
AMGEN CARDIOVASCULAR: ACC 2017 HIGHLIGHTS
49. 49
Provided March 17, 2017, as part of an oral presentation and is qualified by
such, contains forward-looking statements, actual results may vary
materially; Amgen disclaims any duty to update.
• One of the largest CV outcomes trials, including not only those with prior heart attack, but also
prior stroke and symptomatic peripheral artery disease
• Patients were on optimized statin therapy and other CV therapies
• 20% RRR in “hard” MACE composite endpoint of MI, stroke or CV death despite relatively
short (2.2 year) duration of therapy and best current care background therapy—25% RRR
beyond year 1
– Fatal and nonfatal MI or stroke: RRR = 33% beyond year 1
• Effect on CV outcomes extends to LDL-C levels as low as 20 mg/dL, consistent with the effect
seen on atherosclerotic plaque in GLAGOV, with no new safety issues identified
• We look forward to working with payers to improve the health of these high-risk patients,
and have several innovative financial risk sharing programs
• We estimate at least 100,000 heart attacks and strokes could have been avoided last year in
the U.S. alone if all of the appropriate on-label high-risk patients were treated with Repatha®
SUMMARY