Asthma, AstraZeneca, Author Interviews / 01.12.2020

MedicalResearch.com Interview with: Frank Trudo, MD MBA Vice President, US Medical, Respiratory & Immunology AstraZeneca  MedicalResearch.com: What is the background for this study? Response: PONENTE is a multicenter, open-label, single-arm, Phase IIIb trial to evaluate the efficacy and safety of reducing daily oral corticosteroids (OCS) use after initiation of 30 mg dose of FASENRA (benralizumab) administered subcutaneously in adult patients with severe eosinophilic asthma on high-dose inhaled corticosteroids plus long-acting beta2-agonist and long-term use of OCS therapy with or without additional asthma controller(s). The trial expands on OCS-sparing data previously seen in the ZONDA Phase III trial by using a faster steroid tapering schedule in patients who did not experience adrenal insufficiency to reduce OCS use from higher doses. Compared to published trials of other biologics, PONENTE has a personalized OCS tapering schedule that allows for more rapid OCS tapering from higher OCS doses, followed by an assessment of the adrenal function as part of decision-making to manage the risk of adrenal insufficiency. PONENTE also has a longer maintenance phase (approximately 24-32 weeks), allowing assessment of the durability of OCS reduction. FASENRA is a monoclonal antibody that binds directly to IL-5 receptor alpha on eosinophils and attracts natural killer cells to induce rapid and near-complete depletion of eosinophils via apoptosis (programmed cell death). MedicalResearch.com: How is it administered?  Response: FASENRA is injected under your skin (subcutaneously) one time every 4 weeks for the first 3 doses, and then every 8 weeks. In 2019, FASENRA was approved in the US for self-administration in a single dose prefilled autoinjector, the FASENRA pen. (more…)
AstraZeneca, Author Interviews, Cancer Research, ESMO, Lung Cancer, NEJM, Yale / 08.10.2020

MedicalResearch.com Interview with: Roy S. Herbst, M.D., Ph.D. Ensign Professor of Medicine (Medical Oncology) and Professor of Pharmacology Chief of Medical Oncology Yale Cancer Center and Smilow Cancer Hospital Associate Cancer Center Director for Translational Research Yale Cancer Center  MedicalResearch.com: What is the background for this study? How does osimertinib differ from prior versions of EGFR-TKI Inhibitors? o   ADAURA is a randomized, double-blinded, global and placebo-controlled Phase III trial in the adjuvant treatment of 682 patients with Stage IB, II, and IIIA EGFRm NSCLC following complete tumor resection and adjuvant chemotherapy as indicated. Patients were treated with osimertinib 80 mg once-daily oral tablets or placebo for three years or until disease recurrence. The primary endpoint is disease free survival (DFS) in Stage II and IIIA patients, and a key secondary endpoint is DFS in Stage IB, II and IIIA patients. Osimertinib is not currently approved in the adjuvant setting in any country. o   Osimertinib is a third-generation, irreversible EGFR-TKI with clinical activity against central nervous system metastases. The results of the Phase III ADAURA trial of osimertinib demonstrate for the first time in a global trial that an EGFR inhibitor can change the course of early-stage EGFR-mutated lung cancer for patients. o   ADAURA results were first presented in May during the American Society of Clinical Oncology ASCO20 Virtual Scientific Program. (more…)
AstraZeneca, Author Interviews, Pulmonary Disease / 22.08.2020

MedicalResearch.com Interview with: Frank Trudo, MD MBA Vice President, US Medical Affairs Respiratory & Immunology AstraZeneca  MedicalResearch.com: What is the background for this study? Response: ETHOS was a randomized, double-blinded, multi-center, parallel-group, 52-week trial to assess the efficacy and safety of PT010 in symptomatic patients with moderate to very severe COPD and a history of exacerbation(s) in the previous year. A subset of patients participated in the 4-hour pulmonary function test (PFT) sub-study, with the following primary endpoints: change from baseline in morning pre-dose trough FEV1 at Week 24 at (both doses of budesonide/glycopyrrolate/formoterol fumarate MDI versus glycopyrrolate/formoterol fumarate MDI), and FEV1 area under the curve from 0-4 hours at Week 24 (both doses of budesonide/glycopyrrolate/formoterol fumarate MDI vs budesonide/formoterol fumarate MDI).  (more…)
Asthma, AstraZeneca, Author Interviews / 22.08.2020

MedicalResearch.com Interview with: Frank Trudo, MD MBA Vice President, US Medical Affairs Respiratory & Immunology AstraZeneca     MedicalResearch.com: What is the background for this study?
  • Multiple pathways drive asthma. T2 inflammation-driven asthma is present in many patients with severe asthma and is typically characterized by elevated levels of T2 inflammatory biomarkers, including blood eosinophils, serum IgE and fractional exhaled nitric oxide.
    • Some patients with severe asthma do not present with increased T2 inflammation. However, currently available biologic therapies only target T2-driven inflammation.
  • The PATHWAY trial evaluated the efficacy and safety of three dose regimens of tezepelumab versus placebo as an add-on therapy in patients with a history of asthma exacerbations and uncontrolled asthma despite receiving inhaled corticosteroids/long-acting beta2-agonists with or without oral corticosteroids and additional asthma controllers. Overall, the trial showed tezepelumab significantly reduced annualized asthma exacerbation rates of 71%.
  • This post-hoc analysis presented virtually at ATS evaluated the effect of Tezepelumab treatment on asthma exacerbation rates on a seasonal and weekly basis.
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AstraZeneca, Author Interviews, NEJM, Pulmonary Disease / 29.06.2020

MedicalResearch.com Interview with: Frank Trudo, MD MBA Vice President, US Medical Affairs Respiratory & Immunology AstraZeneca MedicalResearch.com: What is the background for this study? Response: ETHOS is a randomized, double-blinded, multi-center, parallel-group, 52-week trial to assess the efficacy and safety of PT010 in symptomatic patients with moderate to very severe COPD and a history of exacerbation(s) in the previous year. Outcomes in the ETHOS trial included, as a primary endpoint, the rate of moderate or severe exacerbations. MedicalResearch.com: How does PT010 differ from other treatments for COPD?
  • Highly competitive: PT010’s Phase III clinical trial program demonstrates it has a highly competitive clinical profile in decreasing moderate or severe exacerbations. Severe exacerbations were defined as exacerbations leading to hospitalization or death.
  • All-cause mortality: In a secondary endpoint, PT010 showed a 46% reduction in the risk of all-cause mortality compared with glycopyrronium/formoterol fumarate. The data from ETHOS show that reducing risk of all-cause mortality is achievable for patients with this progressive disease and could transform treatment goals in COPD.
  • Two potential dose options: This is also the first time we have seen the benefit of closed triple-combination therapy at two ICS doses, which could transform care by allowing physicians to select the optimal dosing option for individual patients. 
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ASCO, AstraZeneca, Author Interviews, Cancer Research, Melanoma / 13.06.2020

MedicalResearch.com Interview with: Yuanbin Chen, MD, PhD Cancer & Hematology Centers of Western Michigan MedicalResearch.com: What is the background for this study? What are the main findings?
    • Response: The CASPIAN trial was a randomized, open-label, multi-center global Phase III trial in the first-line treatment of patients with extensive-stage small cell lung cancer (ES-SCLC). The trial compared IMFINZI in combination with etoposide and either carboplatin or cisplatin chemotherapy, or IMFINZI and chemotherapy with the addition of a second immunotherapy, tremelimumab, versus chemotherapy alone – the primary endpoint being overall survival (OS). After a median follow up of more than two years, the latest results for IMFINZI plus chemotherapy demonstrate a sustained and clinically meaningful OS benefit for patients with extensive-stage small cell lung cancer (ES-SCLC), maintaining a 25% reduction in the risk of death versus chemotherapy alone. Updated median OS was 12.9 months versus 10.5 for chemotherapy.
      • In a post-hoc analysis, 22.2% of patients treated with IMFINZI plus chemotherapy remained alive after 24 months, versus 14.4%, for chemotherapy alone.
      • Post-hoc analysis also showed that for IMFINZI plus chemotherapy, 11.0% of patients were alive and progression-free at 24 months versus 2.9% for chemotherapy alone.
      • IMFINZI plus chemotherapy maintained a high confirmed objective response rate (ORR) (68% versus 58%) and in a post-hoc analysis, duration of response (DoR) for IMFINZI at 24 months was 13.5% versus 3.9% for chemotherapy alone.
      • At 24 months, 12% of patients in the IMFINZI plus chemotherapy arm remained on IMFINZI treatment.]
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ASCO, AstraZeneca, Author Interviews, Cancer Research, Lung Cancer, Yale / 13.06.2020

MedicalResearch.com Interview with: Roy S. Herbst, MD, PhD Ensign Professor of Medicine (Medical Oncology) Professor of Pharmacology Chief of Medical Oncology, Yale Cancer Center and Smilow Cancer Hospital; Associate Cancer Center Director for Translational Research Yale Cancer Center MedicalResearch.com: What is the background for this study? What are the main findings?
  • ADAURA is the first global trial for an EGFR tyrosine kinase inhibitor to show statistically significant and clinically meaningful benefit in adjuvant treatment of Stage IB, II, and IIIA EGFRm NSCLC. The results demonstrated unprecedented disease free survival (DFS) in the adjuvant treatment of these patients after complete tumor resection with curative intent. Osimertinib was assessed against placebo for a treatment duration of up to three years and then unblinded two years earlier than expected at the recommendation of the Independent Data Monitoring Committee (IDMC), based on its determination of overwhelming efficacy during a planned safety analysis.
  • In the primary endpoint of DFS in patients with Stage II and IIIA disease, adjuvant (after surgery) treatment with osimertinib reduced the risk of disease recurrence or death by 83% (based on a hazard ratio [HR] of 0.17; 95% confidence interval [CI] 0.12, 0.23; p<0.0001).
  • DFS results in the overall trial population, Stage IB through IIIA, a key secondary endpoint, demonstrated a reduction in the risk of disease recurrence or death of 79% (based on a HR of 0.21; 95% CI 0.16, 0.28; p<0.0001).
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AstraZeneca, Author Interviews, Rheumatology / 11.06.2020

MedicalResearch.com Interview with: Richard Alan Furie, MD Professor, Center for Autoimmune, Musculoskeletal and Hematopoietic Diseases Feinstein Institutes for Medical Research Chief, Division of Rheumatology, Northwell Health Professor of Medicine, Donald and Barbara Zucker School of Medicine Hofstra/Northwell MedicalResearch.com: What is the background for this study? Response: It has been known for decades that type I interferons play a role in SLE pathogenesis, and therefore the burning question has been whether inhibitors of these pro-inflammatory cytokines would reduce SLE disease activity and could be used as a therapeutic.  There are several strategies for inhibiting the type I interferon pathway, but a conventional approach is to create an antibody against the target protein. The first few clinical trials in SLE evaluated monoclonal antibodies to alpha interferon.  Results were modest at best.  Since this approach only inhibited one (alpha) of five type I interferon subtypes, there were still four subtypes unaffected that could provoke inflammation.  A rather crucial piece of information is that all five subtypes bind to the same receptor.  Therefore, if the receptor is blocked as opposed to a single cytokine, the entire type I interferon family of proteins would be prevented from binding the receptor. This was accomplished with anifrolumab. The phase 2 study in SLE (known as MUSE), which yielded very robust results, was reported several years ago.  It served as a foundation for the phase 3 program, which consisted of two pivotal studies known as TULIP-1 and TULIP-2. Both studies were reported at the 2019 American College of Rheumatology meeting in November, 2019.  Although TULIP-1 did not achieve the primary endpoint, several secondary endpoints were met.  TULIP-2 was successful.  Between all three studies, approximately 1000 patients were enrolled.  Taking advantage of these large numbers, additional analyses of the combined datasets afforded our ability to answer questions about the effects of anifrolumab that were not previously addressed with greater power. In the narrative that accompanied my presentation, I stated “In lupus, disease activity begets damage, and damage begets more damage.  The long-term sequelae of heightened disease activity, better known as flare, are significant.  Regardless of how flare is defined or measured, a major goal is to prevent flare. It is quite justified to think a drug that reduces lupus disease activity should also prevent flares. Well, the proof is in the pudding. In this analysis, we evaluated the effects of anifrolumab on flares.  Recall that anifrolumab targets the type I interferon receptor, blocking all 5 type I subtypes.  The phase 2 MUSE study yielded robust results as did the phase 3 TULIP-2 study.  While, the phase 3 TULIP-1 study did not achieve its primary endpoint, many secondary endpoints showed benefit. In this study, we focused on flare, and examined TULIP-1 and 2 individually as well as pooled data from both studies.”  (more…)
ASCO, AstraZeneca, Author Interviews, Breast Cancer, Cancer Research / 02.06.2020

MedicalResearch.com Interview with: Josefa Briceno, MD Medical Head, DDR/ADC Franchise AstraZenca  MedicalResearch.com: What is the background for this study? What are the main findings? Response: In January 2018, the US FDA expanded the approved use of LYNPARZA to treat patients with HER2- negative metastatic breast cancer with germline BRCA mutations based on positive results from the Phase III OlympiAD trial, which demonstrated the benefit of LYNPARZA over standard of care in physician’s choice chemotherapy in this patient population. LUCY is a Phase IIIb interim analysis aimed to evaluate the clinical effectiveness and safety of LYNPARZA in a real-world setting and has been expanded to include a group of patients with somatic BRCA mutations. A total of 252 patients with HER2-negative metastatic breast cancer with germline BRCA mutations were enrolled in the open-label, single-arm, Phase IIIb study. Patients received a taxane and/or anthracycline in the (neo)adjuvant/metastatic setting, and ≤2 lines of chemotherapy. The primary end point of the study was investigator-defined progression-free survival (PFS), and secondary end points included overall survival, time to first subsequent therapy or death, and investigator-assessed clinical response rate. The interim analysis was planned to take place after 160 progression-free survival events. Overall, treatment lasted for a median of 7.9 months, and the median progression-free survival was 8.1 months (95% confidence interval of 6.9-8.7; 166 progression-free survival events). In addition, the median time to first subsequent therapy or death was 9.7 months (95% confidence interval of 8.7-11.1) and the investigator-assessed clinical response rate was 48.6% (95% confidence interval of 42.2-55.0). Adverse events of all grades were reported in >20% of patients were nausea, anemia, asthenia, vomiting, and fatigue. Grade ≥3 adverse events were reported in 24.6% of patients, and 4.4% of patients had an adverse event that led to treatment discontinuation. (more…)
ASCO, AstraZeneca, Author Interviews, Cancer Research, Ovarian Cancer / 02.06.2020

MedicalResearch.com Interview with: Mark Sims US Franchise Head Women’s Cancer & DNA Damage Response AstraZeneca  MedicalResearch.com: What is the background for this study? What are the main findings? Response: SOLO2 is a Phase III, randomized, double-blind, multicenter trial designed to determine the efficacy and safety of LYNPARZA tablets as a maintenance monotherapy compared with placebo, in patients with platinum-sensitive relapsed or recurrent gBRCA-mutated (BRCAm) ovarian cancer. The trial included 295 patients with germline BRCA1 or BRCA2 mutations who had received at least 2 prior lines of platinum-based chemotherapy and were in complete or partial response. The trial met its primary endpoint in October 2016, showing maintenance treatment with LYNPARZA significantly improved progression-free survival to a median of 19.1 months vs 5.5 months with placebo (a hazard ratio of 0.30; a 95% confidence interval of 0.22 to 0.41; a p value of <0.0001). (more…)
Asthma, AstraZeneca, Author Interviews / 06.05.2020

MedicalResearch.com Interview with: Ubaldo Martin MD VP Clinical Respiratory RIA Late Stage Development AstraZeneca MedicalResearch.com: What is the background for this study? Response: BORA was an extension study evaluating the long-term safety and specific aspects of efficacy in patients who had previously been in the benralizumab pivotal studies.  After the patients completed the pivotal studies (Calima, Sirocco and Zonda), they were eligible to join BORA which followed adults for an additional year and adolescent for an additional 2 years.  All patients receive one of two dosages of benralizumab.  The abstract reports the outcomes of adolescents in the BORA study who were followed for approximately 3 years in total. (more…)
Allergies, Asthma, AstraZeneca, Author Interviews / 01.05.2020

MedicalResearch.com Interview with: astrazenecaOlga Ryan, DrPH, MPH, MBA Regional Clinical Account Director, Southwest AstraZeneca  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Asthma is common and imparts a substantial societal burden. It is well documented that asthma prevalence varies between males and females. Before puberty, more boys have asthma.  Following puberty, a greater proportion of women suffer with asthma. We also have observed that women experience greater morbidity from the illness, greater healthcare resource utilization and suboptimal response for guideline recommended therapies (ICS, ICS/LABA). Rationale for this study focused on describing asthma related outcomes between a well characterized severe asthma cohort, with intent in delineating differences among the sexes. With the advent of targeted biological medicines for severe asthma, as well as apparent gaps in knowledge, we wanted to understand potential sex-specific disease indicators in a well characterized severe asthma cohort. (more…)
Asthma, AstraZeneca, Author Interviews, Cost of Health Care / 01.05.2020

MedicalResearch.com Interview with: Yen Chung, PharmD Payer Evidence Director US Medical Affairs, AstraZeneca MedicalResearch.com: What is the background for this study? Response: Among patients with persistent asthma, use of systemic corticosteroids (SCS) is typically reserved for treatment of asthma exacerbations and as a supplemental maintenance therapy for patients whose disease remains uncontrolled with maximum maintenance controller therapies. However, SCS therapy comes with known risks for acute and chronic complications. It is well established that patients with severe asthma are responsible for a disproportionate amount of the economic burden of asthma;  however, less clear is the extent to which systemic corticosteroids use and its consequences specifically contributes to the cost burden of asthma. The purpose of this study was to use administrative claims to follow asthma patients with and without SCS treatment for up to 3 years and compare their complication rates, health care resource utilization, and costs.  (more…)
AstraZeneca, Author Interviews, Diabetes, Heart Disease, JAMA / 01.04.2020

MedicalResearch.com Interview with: John J. V. McMurray,  MD FRCP FESC FACC FAHA FRSE FMedSci British Heart Foundation Cardiovascular Research Centre University of Glasgow Glasgow, United Kingdom  Kieran F Docherty DAPA-HF investigator British Heart Foundation Cardiovascular Research Centre, University of Glasgow     MedicalResearch.com: What is the background for this study? Response: DAPA-HF was a double-blind randomized controlled trial comparing dapagliflozin 10 mg once daily with placebo in 4744 patients with heart failure and reduced ejection fraction (HFrEF). The primary outcome was a composite of time to occurrence of a worsening heart failure event (principally heart failure hospitalization) or cardiovascular death, whichever came first. Dapagliflozin reduced the primary outcome by 26% and reduced the risk of each of heart failure hospitalization and cardiovascular death individually, as well as overall mortality. Patient symptoms were also improved. The aim of the present report was to examine the effect of dapagliflozin separately in patients with and without type 2 diabetes at baseline (45/55% split in the trial). The reason for this was that dapagliflozin was originally introduced as a glucose-lowering medication for the treatment of type 2 diabetes. We find that dapagliflozin was equally beneficial in patients with and without diabetes and was as well tolerated in patients without diabetes as in those with diabetes. More remarkably, among the patients without diabetes, dapagliflozin was as effective in participants with a completely normal glycated haemoglobin (HbA1c) as in those with prediabetes. In patients with a normal HbA1c, dapagliflozin did not lead to any reduction in HbA1c, but did improve clinical outcomes.  (more…)
AstraZeneca, Author Interviews, Pulmonary Disease / 17.09.2019

MedicalResearch.com Interview from: AstraZeneca Spokesperson MedicalResearch.com: What is the background for this study? Would you briefly explain what is meant by COPD? How common is severe COPD? Response: COPD, or chronic obstructive pulmonary disease, is a progressive disease associated mainly with tobacco smoking, air pollution or occupational exposure, which can cause obstruction of airflow in the lungs making it hard to breathe. In the United States, COPD is the fourth leading cause of death. Its prevalence in adults 18 years of age and older is 6.5 percent. An estimated 16 million people are currently diagnosed with COPD, and millions more are believed to have it but do not know it. ETHOS is a randomized, double-blind, multi-center, parallel-group, 52-week trial to assess the efficacy and safety of PT010 in symptomatic patients with moderate to very severe COPD and a history of exacerbation(s) in the previous year. The trial compared two doses given twice daily of PT010 (320/14.4/9.6mcg and 160/14.4/9.6mcg) with glycopyrrolate/formoterol fumarate (14.4/9.6mcg) and PT009 (320/9.6mcg), all using AEROSPHERETM Delivery Technology in a pressurized metered-dose inhaler (pMDI). Outcomes in the ETHOS trial included, as a primary endpoint, the rate of moderate or severe exacerbations. The Phase III ETHOS trial builds on the Phase III KRONOS data which together show PT010’s ability to reduce exacerbation risk in a broad range of patients with COPD, irrespective of whether they have had an exacerbation in the previous twelve months. (more…)
AstraZeneca, Author Interviews, Brigham & Women's - Harvard, Diabetes, Heart Disease / 10.09.2019

MedicalResearch.com Interview with: 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.  (more…)
AstraZeneca, Author Interviews, Kidney Disease, Mineral Metabolism / 08.07.2019

MedicalResearch.com Interview with: 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. (more…)
AstraZeneca, Author Interviews, Diabetes, Kidney Disease / 24.06.2019

MedicalResearch.com Interview with: 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). (more…)
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. (more…)
Allergies, AstraZeneca, Author Interviews / 01.12.2018

MedicalResearch.com Interview with: 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. 
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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.  (more…)
AstraZeneca, Author Interviews, Kidney Disease / 05.11.2018

MedicalResearch.com Interview with: 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. (more…)
AstraZeneca, Author Interviews, Blood Pressure - Hypertension, Kidney Disease / 05.11.2018

MedicalResearch.com Interview with: 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. (more…)
AstraZeneca, Author Interviews, Kidney Disease, Mineral Metabolism / 05.11.2018

MedicalResearch.com Interview with: 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. (more…)
Asthma, AstraZeneca, Author Interviews, Pulmonary Disease / 20.09.2018

MedicalResearch.com Interview with: 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.
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Asthma, AstraZeneca, Author Interviews, Immunotherapy, Lancet, Pulmonary Disease / 27.06.2018

MedicalResearch.com Interview with: Reynold A. Panettieri, Jr., M.D. Professor of Medicine, Robert Wood Johnson Medical School Vice Chancellor, Clinical & Translational Science Director, Rutgers Institute for Translational Medicine & Science Emeritus Professor of Medicine, University of Pennsylvania Child Health Institute of New Jersey Rutgers, The State University of New Jersey New Brunswick, NJ  08901 MedicalResearch.com: What is the background for this study? Response: Severe asthma is characterized by Type 2 inflammation manifested by increases in IL-13, IL-4 and Il-5 levels in the airways that promotes airway hyperresponsiveness and in part irreversible airway obstruction.  These clinical manifestations profoundly increase asthma morbidity and mortality. To address an unmet therapeutic need, Tralokinumab was developed as a monoclonal antibody targeting soluble IL-13 with the goal of improving lung function and patient reported outcomes while decreasing annual exacerbation rates.  Stratus 1 and 2 represent two identical randomized, double-blind, placebo-controlled, phase 3 clinical trials in severe asthma.  These international trials enrolled approximately 2000 subjects with severe asthma and examined whether Tralokinumab decreased annualized exacerbation rates (AER) as compared with placebo (primary outcome). (more…)
AstraZeneca, Author Interviews, Diabetes / 24.06.2018

MedicalResearch.com Interview with: Chantal Mathieu, MD, PhD Professor of Medicine Clinical and Experimental Endocrinology Catholic University of Leuven, Belgium MedicalResearch.com: What is the background for this study? Response: People with type 1 diabetes (T1D) are confronted often with the inability to achieve satisfactory glycemic control, being good HbA1c, but in particular stable glycemic control, avoiding hyperglycemic events, but also hypoglycemic events, despite novel insulins and novel technologies. Moreover, intensive insulin therapy is often associated with weight gain, leading to an increase in overweight and obesity also in people with T1D. All of these issues affect quality of life. In the DEPICT 2 study we examined the impact of adding a selective SGLT2 inhibitor, dapagliflozin (two doses tested – 5 and 10mg) in a double blinded manner versus placebo to background insulin (MDI or CSII) in people with T1D reaching insufficient glycemic control (HbA1c 7.5-10.5%). Primary endpoint was lowering in HbA1c at 24 weeks and secondary endpoints included insulin dose reduction and weight reduction as well as a composite endpoint of having a HbA1c drop of >=0.5% without severe hypoglycemia. The study ran internationally, with about 1/3 of patients coming from North America, 1/3 from Europe and 1/5 from Asia (Japan). (more…)
AstraZeneca, Author Interviews, Kidney Disease, Mineral Metabolism / 24.05.2018

MedicalResearch.com Interview with: Steven Fishbane, MD, Chief, Division of Kidney Disease and Hypertension, Northwell Health Vice President, Northwell Health for Network Dialysis Services, Northwell Health Professor of Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Lead investigator of the ZS 005 study MedicalResearch.com: What is the background for this announcement? Would you briefly explain what is meant by hyperkalemia?What are the dangers of an elevated potassium and how does LOKELMA differ from prior standard treatments?  Response: Hyperkalemia is when the potassium in the blood rises to potentially harmful levels. High potassium is primarily harmful for the heart. As the potassium level rises the risk for abnormal electrical rhythms or disruption of the heart’s pumping occur. When severe, a high potassium level can cause death. Lokelma has been demonstrated to be effective for lowering potassium levels with a great degree of consistency. It is well tolerated and has a fairly rapid onset of potassium lowering compared to other drugs for the purpose.  (more…)
AstraZeneca, Author Interviews, Boehringer Ingelheim, Diabetes, Eli Lilly, J&J-Janssen, Merck, Pharmacology / 18.10.2017

MedicalResearch.com Interview with: Melanie J Davies CBE MB ChB MD FRCP FRCGP Professor of Diabetes Medicine NIHR Senior Investigator Emeritus Diabetes Research Centre Leicester Diabetes Centre – Bloom University of Leicester MedicalResearch.com: What is the background for this study? What are the main findings? Response:  This was the first study to test the effectiveness of an oral GLP-1 in patients with type 2 diabetes. The main findings were that compared to both placebo and a GLP-1, Semaglutide, delivered by sub-cutaneous injection weekly, the oral therapy delivered once a day produced better results than placebo and similar results to injectable GLP-1 with regard to reductions in HbA1c and weight loss. (more…)
AstraZeneca, Author Interviews, Eli Lilly, Merck / 07.09.2017

MedicalResearch.com Interview with: Dragana Radovanovic, MD  Head of AMIS Plus Data Center Hirschengraben Zürich MedicalResearch.com: What is the background for this study? What are the main findings? Response: What we know so far? When a woman suffers a heart attack she is older, has consequently more cardiovascular risk factors such as hypertension, has more comorbidities, is less likely to receive the same therapies and more likely to die in hospital. Furthermore, we know from many hospital statistics and administrative data bases that in-hospital mortality of acute myocardial infarction patients has been on the decrease from 1970 to the early 2000’s. We then wanted to know what the situation looks like in Switzerland and therefore analyzed in-hospital mortality over the last 20 years with regard to gender, age and therapies. For this study we used the data of the nationwide AMIS Plus registry (Acute Myocardial Infarction in Switzerland) which exists since 1997 and continuously prospectively collects clinical data of patients hospitalized with acute myocardial infarction. We have found that during the last 20 years (from 1997 to the end of 2016) in-hospital mortality of patients with acute myocardial infarction in Switzerland has halved. Although in-hospital mortality was consistently higher in women, overall age-adjusted mortality has decreased more prominently in women compared to men. Especially in patients aged below 60 years a significant decrease in in-hospital mortality was observed in women but not in men. (more…)