AstraZeneca, Author Interviews, Brigham & Women's - Harvard, Diabetes, Heart Disease / 10.09.2019

MedicalResearch.com Interview with: [caption id="attachment_51229" align="alignleft" width="200"]Dr. David Berg MD Senior Fellow in Cardiovascular Medicine and Critical Care Medicine Brigham and Women’s Hospital Postdoctoral Research Fellow with the TIMI Study Group. Dr. David Berg[/caption] Dr. David Berg MD Senior Fellow in Cardiovascular Medicine and Critical Care Medicine Brigham and Women’s Hospital Postdoctoral Research Fellow with the TIMI Study Group. MedicalResearch.com: What is the background for this study? Response: Heart failure is a frequent and important complication of type 2 diabetes mellitus (T2DM), but there are limited tools for identifying which patients with T2DM are at the highest risk of developing heart failure. In this study, we developed and validated the TIMI Risk Score for Heart Failure in Diabetes [TRS-HF(DM)], a novel clinical risk score that identifies patients with T2DM who are at heightened risk for hospitalization due to heart failure. Fortunately, the risk score also identifies patients who have the greatest absolute reduction in the risk of hospitalization for heart failure with a new class of glucose-lowering therapies called sodium-glucose cotransporter-2 (SGLT2) inhibitors. 
Author Interviews, Diabetes, Heart Disease / 06.09.2019

MedicalResearch.com Interview with: [caption id="attachment_51165" align="alignleft" width="200"]Nicolas Danchin MD, FESC Professor of Medicine, Consultant Cardiologist Intensive Cardiac Care Unit Hôpital Européen Georges Pompidou Paris, France Prof. Danchin[/caption] Nicolas Danchin MD, FESC Professor of Medicine, Consultant Cardiologist Intensive Cardiac Care Unit Hôpital Européen Georges Pompidou Paris, France MedicalResearch.com: What is the background for this study? Response: FAST-MI is a programme of nationwide French surveys, carried out every 5 years in France since 2005 in patients hospitalised with STEMI or NSTEMI. Patients are included consecutively for one month and 10-year follow-up is organized. We can thus analyse patients' outcomes in relation with their profile. Knowing that diabetic patients represent a large proportion of patients with AMI, we thought it would be worthwhile determining whether they suffered specific complications, and in particular, heart failure, both at the acute stage and in the subsequent months.
AstraZeneca, Author Interviews, Kidney Disease, Mineral Metabolism / 08.07.2019

MedicalResearch.com Interview with: [caption id="attachment_50153" align="alignleft" width="142"]Steven Fishbane MD Chief, Division of Kidney Disease and Hypertension Vice President, Northwell Health for Network Dialysis Services, Northwell Health Professor of Medicine Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Department of Medicine, Zucker School of Medicine at Hofstra/Northwell, Great Neck, New York Dr. Fishbane[/caption] Steven Fishbane MD Chief, Division of Kidney Disease and Hypertension Vice President, Northwell Health for Network Dialysis Services, Northwell Health Professor of Medicine Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Department of Medicine, Zucker School of Medicine at Hofstra/Northwell, Great Neck, New York  MedicalResearch.com: What is the background for this study? Response: Patients on hemodialysis have a great frequency of hyperkalemia. The hemodialysis treatment removes some potassium but not enough to get rid of this problem. Available medications to bind potassium have not been tested among these patients. The purpose of the study was to see if sodium zirconium cyclosilicate could be used as a potassium binder to reduce the risk of hyperkalemia in patients on a hemodialysis.
AstraZeneca, Author Interviews, Diabetes, Kidney Disease / 24.06.2019

MedicalResearch.com Interview with: [caption id="attachment_49957" align="alignleft" width="200"]Naeem Khan MD Vice President at AstraZeneca Dr. Khan[/caption] Naeem Khan MD Vice President at AstraZeneca  MedicalResearch.com: What is the background for this study? What are the main findings? Response: A pre-specified exploratory analysis of renal data from the DECLARE-TIMI 58 trial, the largest SGLT-2 inhibitor (SGLT-2i) cardiovascular outcomes trial (CVOT) conducted to date, showed that FARXIGA (dapagliflozin) reduced the composite of kidney function decline, end-stage renal disease (ESRD) or renal death by 47% in patients with type 2 diabetes (T2D). Additionally, FARXIGA reduced the relative risk of a cardio-renal composite of kidney function decline, ESRD, or renal or cardiovascular (CV) death by 24% compared to placebo. The analysis evaluated 17,160 patients with type 2 diabetes and predominantly preserved renal function, irrespective of underlying atherosclerotic CV disease (ASCVD).
AstraZeneca, Kidney Disease / 04.06.2019

MedicalResearch.com Interview with: AstraZenecaJill Davis, MS Director, Health Economics and Outcomes Research AstraZeneca  MedicalResearch.com: What is the background for this study? Who is most at risk for hyperkalemia post discharge? Response: In the United States, an estimated 30 million people suffer from chronic kidney disease (CKD), about 3.7 million of which have hyperkalemia (elevated potassium level). Hyperkalemia (HK) can be chronic, so it’s important that those who have been diagnosed with hyperkalemia previously or have CKD have their potassium levels monitored by their healthcare provider. Additionally, although HK is estimated to be prevalent in more than 66,000 emergency department (ED) visits annually, there is limited knowledge about the management of patients with HK in the ED setting and post-discharge. We decided to focus our study to better understand and compare the ED management and post-discharge outcomes among patients with varying levels of hyperkalemia To conduct this study, we analyzed the electronic medical record data from the Research Action for Health Network (2012-2018) of 6,222 adult patients with a randomly selected HK-related ED visit. We concluded that improved management of HK patients in the ED and post-discharge period is needed to reduce the recurrence of hyperkalemia.
Author Interviews, Breast Cancer, Chemotherapy, NEJM / 27.03.2019

MedicalResearch.com Interview with: [caption id="attachment_48191" align="alignleft" width="150"]Rita Mehta, MD, HS Clinical Professor,Chao Family Comprehensive Cancer CenterUniversity of California School of Medicine, Irvine  Dr. Mehta[/caption] Rita Mehta, MD, HS Clinical Professor, Chao Family Comprehensive Cancer Center University of California School of Medicine, Irvine  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Most patients with HR-positive breast cancer become resistant to hormonal therapies like aromatase inhibitor-anastrozole over time, and downregulating estrogen receptor was identified as a mechanism for overcoming or delaying resistance to hormonal therapy in advanced HR-positive breast cancer. The prospective, randomized phase III S0226 trial, first reported by us in NEJM 2012, showed that the selective estrogen receptor degrader fulvestrant in combination with anastrozole significantly improved progression-free survival in 707 women with HR-positive metastatic breast cancer in first-line setting. Treatment with the selective estrogen receptor degrader (SERD) fulvestrant achieved a clinically significant and meaningful improvement in overall survival in patients with hormone receptor (HR)-positive advanced breast cancer in first-line therapy, according to the final analysis of overall survival results from the S0226 study reported by us (Mehta et al. NEJM 2019)
  • Results showed that median overall survival improved by 7.8 months with anastrozole plus fulvestrant (median overall survival = 49.8 months) compared to anastrozole (median overall survival = 42.0 months).
  • The improvement was even greater in patients with endocrine naive disease, with an absolute improvement in median overall survival of 11.9 months.
  • No new safety signals were observed with longer follow-up. 
Allergies, AstraZeneca, Author Interviews / 01.12.2018

MedicalResearch.com Interview with: [caption id="attachment_46299" align="alignleft" width="125"]Mr. Tosh Butt Vice President, Respiratory AstraZeneca Mr. Butt[/caption] Mr. Tosh Butt Vice President, Respiratory AstraZeneca Mr. Butt discusses the recent announcement that the FDA has granted Orphan Drug Designation for Fasenra for the treatment of Eosinophilic Granulomatosis with Polyangiitis.  MedicalResearch.com: What is the background for this announcement? Can you tell us a little more about Eosinophilic Granulomatosis with Polyangiitis/Churg Strauss? How does it differ/resemble severe eosinophilic asthma?
  • The US Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) for FASENRA™ (benralizumab) for the treatment of Eosinophilic Granulomatosis with Polyangiitis (EGPA). The ODD application was based on epidemiology demonstrating the rarity of the disease (<200k US patients) and a scientific rationale that FASENRA may benefit patients with this condition. The core role of eosinophilia in EGPA and FASENRA’s demonstrated eosinophil-depleting properties provided this rationale and suggest it may deliver benefit to patients with EGPA.
  • EGPA is a rare autoimmune disease that can cause damage to multiple organs and tissues. EGPA is characterized by inflammation of blood vessels and the presence of elevated levels of eosinophils, a type of white blood cell. All patients with EGPA have very high levels of eosinophils at some point in their disease. FASENRA induces rapid and near-complete depletion of eosinophils in the blood and has proven efficacy in severe eosinophilic asthma, which suggest it may deliver benefit to patients with EGPA. 
Asthma, AstraZeneca, Author Interviews, Pulmonary Disease / 22.11.2018

MedicalResearch.com Interview with: “Asthma Inhaler” by NIAID is licensed under CC BY 2.0Sean O'Quinn MPH Director, Patient Reported Outcomes AstraZeneca  MedicalResearch.com: What is the background for this study? How does benralizumab differ from traditional medications for asthma? Response:  FASENRA™ (benralizumab 30mg for subcutaneous injection as add-on maintenance therapy in severe eosinophilic asthma for patients 12 years and older) has a strong clinical profile, including powerful efficacy against exacerbations and the ability to improve lung function. Benralizumab is a respiratory biologic that binds directly to the IL-5α receptor on eosinophils and attracts natural killer cells to induce rapid and near-complete depletion of eosinophils via apoptosis. (NOTE: The mechanism of action of FASENRA in asthma has not been definitively established.) Benralizumab is not indicated for treatment of other eosinophilic conditions or for relief of acute bronchospasm or status asthmaticus. The most common adverse reactions include headache and pharyngitis. Dependence on rescue medications is indicative of poor asthma control. In the Phase III SIROCCO/CALIMA trials, patients with severe eosinophilic asthma had significantly reduced exacerbation frequency and improved lung function when treated with benralizumab 30mg Q8W (first three doses Q4W) vs. placebo. Less was known about the effects of benralizumab on rescue medication usage—specifically daily total rescue medication use, daytime and nighttime rescue medication use, and nighttime awakenings requiring rescue medication use. The aim of this analysis was to understand the potential treatment effects of benralizumab on these parameters. 
AstraZeneca, Author Interviews, Kidney Disease / 05.11.2018

MedicalResearch.com Interview with: [caption id="attachment_45705" align="alignleft" width="125"]Dr-Danilo Verge.png Dr. Verge[/caption] Danilo Verge MD MBA Vice President, CVRM Global Medical Affairs AstraZeneca MedicalResearch.com: What is the background for this study? Response: Dapagliflozin, an SGLT2 inhibitor (sodium-glucose co-transporter 2), has been shown to improve glycemic control by decreasing glucose reabsorption in the kidneys and inducing urinary glucose clearance. SGLT2 inhibitors have also been shown to be effective in lowering albuminuria and stabilizing eGFR (estimated glomerular filtration rate). The effect of dapagliflozin on UACR (urine albumin-to-creatinine ratio) has been shown to vary among patients. The objective of this post-hoc analysis, based on the pooled data from 11 randomized, placebo-controlled clinical trials, was to assess baseline characteristics and concurrent changes in cardiovascular (CV) risk markers associated with UACR response to dapagliflozin.
AstraZeneca, Author Interviews, Blood Pressure - Hypertension, Kidney Disease / 05.11.2018

MedicalResearch.com Interview with: [caption id="attachment_45702" align="alignleft" width="125"]Lei Qin Lei Qin[/caption] Lei Qin MS Director, Health Economics and Payer Analytics AstraZeneca MedicalResearch.com: What is the background for this study? Response: Renin-angiotensin-aldosterone system inhibitors (RAASi) are guideline-recommended therapies for patients with chronic kidney disease (CKD), but are commonly prescribed at suboptimal doses, which has been associated with worsening clinical outcomes. The objective of our study was to estimate the real-world associations between RAASi dose and adverse clinical outcomes in patients prescribed RAASi therapies with new-onset CKD in the UK.
AstraZeneca, Author Interviews, Kidney Disease, Mineral Metabolism / 05.11.2018

MedicalResearch.com Interview with: [caption id="attachment_45698" align="alignleft" width="125"]Rahul Agrawal MD PhD VP, Global Medicines Leader AstraZeneca Dr. Agrawal[/caption] Rahul Agrawal MD PhD VP, Global Medicines Leader AstraZeneca MedicalResearch.com: What is the background for this study?   About the study: HARMONIZE Global is a Phase III, randomized, multicenter, double-blind, placebo-controlled trial involving 267 patients with hyperkalemia (mean potassium levels greater than 5.0 mEq/L) in 47 study locations across the Asia Pacific region, which will support registration in Japan, Taiwan, Korea and Russia. Study design: The trial design of HARMONIZE Global is similar to HARMONIZE (NCT02088073) but evaluated two doses of LOKELMATM (sodium zirconium cyclosilicate) instead of three, as well as patients in different geographical regions.
Asthma, AstraZeneca, Author Interviews, Pulmonary Disease / 20.09.2018

MedicalResearch.com Interview with: [caption id="attachment_44683" align="alignleft" width="200"]Tosh Butt, MBA VP Respiratory AstraZeneca Tosh Butt[/caption] Tosh Butt, MBA VP Respiratory AstraZeneca MedicalResearch.com: What is the background for this study? How is benralizumab different from more traditional treatments for asthma?
    • BORA is a randomized, double-blind, parallel-group, Phase III extension, and is one of six Phase III trials in the WINDWARD program in asthma. The current analysis includes results for 1,926 patients from the two placebo controlled exacerbation trials, SIROCCO (48 week) and CALIMA (56 weeks). BORA provides evidence that add on maintenance treatment with FASENRA (benralizumab) resulted in a consistent safety profile over a second year of treatment, with no increase in the frequencies of overall or serious adverse events, and sustained efficacy in terms of reducing asthma exacerbations, and improving lung function and asthma symptoms. The BORA trial results could provide confidence to patients with severe eosinophilic asthma and physicians that the positive outcomes they may be seeing with benralizumab can be maintained over a second year of treatment.
  • FASENRA, a different kind of respiratory biologic, has a strong clinical profile which includes the ability to show lung function improvement after the first dose, the potential to reduce – or even stop - oral steroid use, and the convenience of 8-week dosing (no other respiratory biologic offers this dosing). FASENRA is approved for add-on maintenance treatment of patients with severe asthma ages 12 years and older, and with an eosinophilic phenotype. FASENRA binds directly to the IL-5a receptor on an eosinophil and uniquely attracts natural killer cells to induce apoptosis, or cell death. Other biologics currently available are anti-IL5s – a passive approach that primarily acts to block differentiation and survival of the eosinophil.