Author Interviews, Bristol Myers Squibb, Rheumatology, Smoking / 24.10.2018

MedicalResearch.com Interview with: [caption id="attachment_45370" align="alignleft" width="90"]Pr Gilles Boire, M.D., M. ScService de rhumatologie Département de médecine Faculté de médecine et des sciences de la santé Université de Sherbrooke Prof. Boire[/caption] Pr Gilles Boire, M.D., M. ScService de rhumatologie Département de médecine Faculté de médecine et des sciences de la santé Université de Sherbrooke MedicalResearch.com: What is the background for this study? Response: Rheumatoid arthritis (RA) patients are heterogeneous at initial presentation, in response to treatments and according to their outcomes. No clinical features and very few biomarkers, except autoantibodies such as anti-Cyclic Citrullinated Peptides/Proteins (CCP), identify patients with divergent prognostic trajectories. To help improve early prognostic classification, we initiated 20 years ago the single center longitudinal observational Early Undifferentiated PolyArthritis (EUPA) study of consecutive patients presenting with recent-onset inflammatory polyarthritis, 90% of which fulfill classification criteria for RA at baseline. Our registry includes 739 very early RA patients (median symptom duration 3.6 months), rapidly treated to joint remission (i.e. 0/66 swollen joint) and followed over 5 years. Each patient visit is linked to biosamples and to sequential radiographs scored according to the modified Sharp/van der Heijde method. As we had the clinical impression that clinical features of recruited patients were evolving, we compared patients from 3 periods (1998-2004; 2005-2010; 2011-2017). 
Abbott, Author Interviews, Biomarkers, Heart Disease, JAMA / 20.10.2018

MedicalResearch.com Interview with: [caption id="attachment_45305" align="alignleft" width="137"]Dr John W Pickering, BSc(Hons), PhD, BA(Hons) Associate Professor , Senior Research Fellow in Acute Care Emergency Care Foundation, Canterbury Medical Research Foundation, Canterbury District Health Board |  Christchurch Hospital Research Associate Professor | Department of Medicine University of Otago Christchurch Prof. Pickering[/caption] Dr John W Pickering, BSc(Hons), PhD, BA(Hons) Associate Professor , Senior Research Fellow in Acute Care Emergency Care Foundation, Canterbury Medical Research Foundation, Canterbury District Health Board |  Christchurch Hospital Research Associate Professor | Department of Medicine University of Otago Christchurch MedicalResearch.com: What is the background for this study? What are the main findings? Response: The assessment of patients with suspected myocardial infarction is one of the most common tasks in the emergency department. Most patients assessed (80 to 98% depending on the health system) are ultimate not diagnosed with an MI.   High-sensitivity troponin assays have been shown to have sufficient precision at low concentrations to allow very early rule-out of myocardial infarction. However, these are lab-based assays which typically result in a delay from blood sampling before the result is available and the physician is able to return to a patient to make a decision to release the patient or undertake further investigation. Point-of-care assays provide results much quicker, but have to-date not had the analytical characteristics that allow precise measurements at low concentrations. In this pilot study we demonstrated that a single measurement with a new point-of-care assay (TnI-Nx; Abbott Point of Care) which can measure low troponin concentrations, could safely be used to rule-out myocardial infarction a large proportion of patients (57%). The performance was at least comparable to the high-sensitivity troponin I assay, if not a little better (44%).
Author Interviews, Flu - Influenza, Roche / 11.10.2018

MedicalResearch.com Interview with: [caption id="attachment_45220" align="alignleft" width="200"]Mark D. Eisner, MD, MPH Vice President, Product Development Immunology Infectious Disease and Ophthalmology Genentech  Dr. Eisner[/caption] Mark D. Eisner, MD, MPH Vice President, Product Development Immunology Infectious Disease and Ophthalmology Genentech  MedicalResearch.com: What is the background for this study? Response: CAPSTONE-2 is a Phase III multicenter, randomized, double-blind study that evaluated the efficacy and safety of a single dose of baloxavir marboxil compared with placebo and oseltamivir in people 12 years and older who are at a high risk of complications from the flu. The Centers for Disease Control and Prevention (CDC) defines people at high risk for serious flu complications to include adults 65 years of age or older, or those who have conditions such as asthma, chronic lung disease, morbid obesity or heart disease. A total of 2,184 participants enrolled in the study and were randomly assigned to receive a single, oral dose of 40 mg or 80 mg of baloxavir marboxil (according to body weight), placebo or 75 mg of oseltamivir twice daily for five days. The primary objective of the study evaluated the efficacy of a single dose of baloxavir marboxil compared with placebo by measuring the time to improvement of influenza symptoms. Key secondary endpoints compared outcomes in baloxavir marboxil versus placebo or oseltamivir – these included time to resolution of fever, time to cessation of viral shedding, infectious virus detection in swabs of the nose and throat, prescription of antibiotics and influenza-related complications. Genentech announced initial results from the study on July 16, 2018 but the full data was presented for the first time during a late-breaking oral presentation at the annual IDWeek meeting in San Francisco, CA on October 6, 2018. Baloxavir marboxil is a first-in-class, single-dose investigational oral medicine with a novel proposed mechanism of action designed to target the influenza A and B viruses, including oseltamivir-resistant strains and avian strains (e.g. H7N9, H5N1). Baloxavir marboxil is the first potential influenza treatment to demonstrate a clinically meaningful benefit for people highly vulnerable to serious influenza complications in clinical trials. The FDA accepted a New Drug Application (NDA) and granted Priority Review to baloxavir marboxil as a single-dose, oral treatment for acute, uncomplicated influenza in people 12 years and older. The NDA was based on results from the Phase III CAPSTONE-1 study of a single dose of baloxavir marboxil compared with placebo or oseltamivir 75 mg, twice daily for five days, in otherwise healthy people with the flu. Results from a placebo-controlled Phase II study in otherwise healthy people with the flu were included as supporting data in the NDA. The FDA is expected to make a decision on approval by December 24, 2018.
Author Interviews, Dermatology, Pharmaceutical Companies / 09.10.2018

MedicalResearch.com Interview with: foamixDavid Domzalski CEO Foamix Pharmaceuticals MedicalResearch.com: What is the background for this study?  How does FMX101 differ from other treatment for acne, ie benzoyl peroxide, topical clindamycin etc?  Response: This study measures the safety and efficacy of a topical foam formulation of the antibiotic minocycline, for the treatment of moderate-to-severe acne. Minocycline is one of the most commonly used products for the treatment of acne, but is currently only available in an oral dosage form. Significant side effects are associated with oral minocycline, including GI upset, photosensitivity, headaches, dizziness, and other potential effects on the CNS.  In addition to the side effects associated with oral minocycline, many currently available topical acne medications contain ingredients which can be drying and irritating to the skin.  These side effects can be frustrating to patients and potentially impact overall compliance to their treatment regimen.  The study addresses important unmet needs in dermatology to determine whether providing patients with a topical dosage form of minocycline may have potential advantages over existing products. In our first two Phase 3 clinical studies, >95% of facial local tolerability signs and symptoms were classified as “none” or “mild,” including dryness, erythema and itching.  Also, our topical minocycline foam, FMX101, is a natural triglyceride-based vehicle that does not contain ingredients that serve as  primary irritants or surfactants.  We believe that FMX101, if approved, would be the first topical minocycline available for the treatment of acne and provide a novel and much needed treatment option for patients who suffer from the physical and psycho-social effects of acne.
Abbott, Author Interviews, Flu - Influenza / 08.10.2018

MedicalResearch.com Interview with: [caption id="attachment_45115" align="alignleft" width="200"]Abbott’s molecular point-of-care flu test, ID NOW Abbott’s molecular point-of-care flu test, ID NOW[/caption] Dr. Norman Moore PhD Abbott’s Director of Scientific Affairs for Infectious Diseases  MedicalResearch.com: What is the background for this test? How does ID NOW differ from other tests for influenza? Response: This test was developed to give providers – and their patients – lab-accurate results more quickly than ever, right at the point of care. It was designed for ease of use, as well as to be portable and small enough that it can be used in a broad range of healthcare settings, including walk-in clinics, urgent care centers, doctors’ offices and emergency rooms. Prior to ID NOW, traditional molecular tests offered great performance, but took too long to impact treatment decisions. ID NOW is able to deliver the performance and accuracy of lab-based tests in a timeframe that offers the best chance of improving treatment decisions. 
Author Interviews, Critical Care - Intensive Care - ICUs, Hospital Acquired, Infections, Kidney Disease, Merck / 06.10.2018

MedicalResearch.com Interview with: [caption id="attachment_45072" align="alignleft" width="150"]Michelle Hoffman Brown Associate Principal Scientist at Merck Merck Michelle Brown[/caption] Michelle Hoffman Brown Associate Principal Scientist Merck MedicalResearch.com: What is the background for this study? What are the kidney risks of using colistin to treat carbapenem-resistant bacterial infections? Response: Gram-negative pathogens are responsible for half of all healthcare-associated infections and their ability to resist traditional antibiotics makes them more dangerous for seriously ill patients in a healthcare setting. The need for new approaches to treat these pathogens is essential and this trial aimed to evaluate the efficacy and safety of imipenem/relebactam (IMI/REL) for the treatment of these challenging infections. Nephrotoxicity is a common complication of colistin-based therapy and is the potential adverse experience of greatest concern to prescribing clinicians, limiting its use to treat carbapenem-resistant bacterial infections. Relebactam is a novel β-lactamase inhibitor that restores imipenem activity against many imipenem-non-susceptible strains of Gram-negative pathogens. In the Phase 3 RESTORE-IMI 1 study (NCT02452047), IMI/REL was shown to be as effective as, but better tolerated than, colistin plus imipenem, including as demonstrated by a lower incidence of treatment-emergent nephrotoxicity (prespecified secondary endpoint). This analysis looked at additional renal safety data from the RESTORE-IMI 1 trial. 
ALS, Author Interviews, Pharmaceutical Companies / 27.09.2018

MedicalResearch.com Interview with: RetrotopeRobert J Molinari, Ph.D. President and CEO Retrotope, Inc.   MedicalResearch.com: What is the background for this study? How does RT001 differ from other treatments for neurodegenerative diseases?  Response: Lipid peroxidation in critical cell and mitochondrial membranes represents a common pathway of cell death in many neurodegenerative diseases, regardless of the initiating trigger of original damage, e.g. aberrant gene expression, misfolded proteins such as tau and amyloid, environmental insults, etc. This hypothesis was supported by work showing that stabilizing lipids (using virtually indistinguishable isotopic variants of the original dietary molecules) was able to mitigate disease-related cell dysfunction, and reverse disease in a variety of animal models, and more recently, in human patients enrolled in clinical trials. It has been known for decades that lipid peroxidation detritus of oxidized membrane fats are present in most all diseases of degeneration and aging, including Alzheimer’s disease, Parkinson’s disease, atherosclerosis, ALS, Huntington’s, and fatal inborn genetic errors resulting in neurodegenerative diseases (among others). The hypothesis that controlling such oxidation could provide therapeutic benefit was abandoned when numerous formal trials of classical antioxidants, e.g. Co-enzyme Q, Vitamin E, and others failed to provide meaningful benefit. We believed that the antioxidant mechanism used to attempt control of the membrane oxidation was flawed, but that the target itself was correct. Indeed, by using a new class of oral drugs that are lipids fortified against damage at the key susceptible bonds, we observed reduction in lipid peroxidation damage that halted, and even reversed neurodegenerative disease progression. Dosed in amounts and forms similar to omega 3 and 6 supplements, these drugs exhibited profound disease modification across a broad range of diseases in animal models, placebo controlled- and open label- human trials.
Author Interviews, Cost of Health Care, JAMA, Pharmaceutical Companies / 26.09.2018

MedicalResearch.com Interview with: [caption id="attachment_44730" align="alignleft" width="200"]Thomas J Moore Senior Scientist Institute for Safe Medication Practices Lecturer, Department of Epidemiology and Biostatistics The George Washington University Milken Institute of Public Health Alexandria, VA 22314 Thomas J Moore[/caption] Thomas J Moore AB Senior Scientist Institute for Safe Medication Practices Lecturer, Department of Epidemiology and Biostatistics The George Washington University Milken Institute of Public Health Alexandria, VA 22314 MedicalResearch.com: What is the background for this study? What are the main findings?
  • The study provides realistic cost estimates of pivotal clinical trials that establish drug benefits to support FDA approval of 59 new drugs released for marketing in 2015-2016.
  • The median estimated cost was just $19 million, with half of the 138 trials studied clustered between $12 million and $33 million.
  • The highest cost trials–with estimates up to $345 million–were for new drugs that were similar to drugs already available and already proven in treating serious illnesses. 
Author Interviews, Dermatology, Eli Lilly / 25.09.2018

MedicalResearch.com Interview with: [caption id="attachment_44799" align="alignleft" width="200"]Lotus Mallbris, M.D., Ph.D., Vice president, Immunology Development Lilly Bio-Medicines  Dr. Mallbris[/caption] Lotus Mallbris, M.D., Ph.D., Vice president, Immunology Development Lilly Bio-Medicines  MedicalResearch.com: What is the background for this study? What are the main findings? Response: By exploring creative clinical approaches and patient-centric pathways to more thoroughly address the key aspects of treating these complex conditions, Lilly is bringing innovation forward in hopes of reducing the burden of dermatologic disease for people around the world. The results of the IXORA-S study suggest that Taltz may provide significantly greater clearance of nail psoriasis than ustekinumab. This is significant because nail lesions are a common feature of psoriasis. It’s often associated with discomfort, which can lead to functional impairment and distress, further supporting the importance of complete clearance.  
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.
Author Interviews, Cancer Research, Pharmaceutical Companies / 20.08.2018

MedicalResearch.com Interview with: [caption id="attachment_43995" align="alignleft" width="200"]Jeffrey S. Humphrey, MD President of Kyowa Kirin Pharmaceutical Development, Inc Dr. Humphrey[/caption] Jeffrey S. Humphrey, MD President of Kyowa Kirin Pharmaceutical Development, Inc MedicalResearch.com: What is the background for this announcement? Would you briefly explain what is meant by Mycosis Fungoides and Sézary Syndrome? Response: Kyowya Kirin has received FDA approval for Poteligeo (mogamulizumab), based on findings from the MAVORIC trial. Mogamulizumab is a humanized immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that targets CC chemokine receptor 4 (CCR4), for the treatment of the most common subtypes of cutaneous T-cell lymphoma (CTCL), mycosis fungoides (MF) and Sézary syndrome (SS). MF and SS may have a profound and severe impact on quality of life, including a patient’s functional, emotional and social well-being, as symptoms may include a scaly red rash or light or dark patches in areas of the body that are not usually exposed to the sun; thin, reddened, eczema-like rash; thickened scaly, red skin (or plaques) or psoriasis-like rash; more advanced disease can include tumors (with significant thickness) on the skin, which may develop ulcers and become infected. Because CTCL manifests in skin lesions, it is often mistaken for other skin conditions (early stage MF and SS can be diagnosed as other skin conditions), which can delay conclusive diagnosis and treatment options. MF is the most common subtype of CTCL, affecting 50-70% of individuals. In most patients diagnosed with early stage MF, the skin involvement does not progress, but in some patients, it will slowly progress. SS accounts for approximately 3% of CTCL cases and is a more aggressive, leukemic form of CTCL, affecting the blood, skin, lymph nodes and visceral organs
Author Interviews, HIV, Pharmaceutical Companies / 16.08.2018

MedicalResearch.com Interview with: TaiMed BiologicsStanley Lewis, M.D. TaiMed Biologics Irvine, CA 92614 MedicalResearch.com: What is the background for this study? Response: The phase III clinical trial was conducted to assess the efficacy and safety of Trogarzo™ (ibalizumab-uiyk) injection in patients with multidrug resistant HIV-1. The study design was approved by the FDA. Results obtained were included in the New Drug Application submitted to the FDA which approved Trogarzo™ on March 6, 2018. The phase III, open-label study, enrolled 40 patients with multidrug-resistant (MDR) HIV-1 in whom multiple antiretroviral therapies had failed. All patients at baseline were experiencing viral failure. After a seven-day control period, patients received an intravenous 2000 mg loading dose of Trogarzo™ which was the only change made to their antiretroviral regimen. Through the 24-week treatment period of the study, patients were given a maintenance dose of 800 mg of Trogarzo™ every two weeks along with an optimized background regimen that included at least one additional fully active agent.
Author Interviews, Gastrointestinal Disease, Pharmaceutical Companies / 15.08.2018

MedicalResearch.com Interview with: RedHill Biopharma LtdMr. Gilead Raday, MPhil, MSc Chief Operating Officer RedHill Biopharma Ltd MedicalResearch.com: What is the background for this study? Would you briefly explain what is meant by Crohn's disease?  How common is it and whom does it affect?  Response: Crohn's disease (CD) is a chronic, relapsing inflammatory gastrointestinal disorder characterized by a variety of symptoms, including severe abdominal pain, diarrhea, bleeding, bowel obstruction, fever and weight loss. The underlying cause of Crohn's is unknown; however, CD is believed to arise secondary to genetic and environmental stimuli. More than 1.5 million people suffer from CD globally and it is prevalent in the U.S., affecting more than 200 people per 100,000. The current standard of care for Crohn's disease is limited to anti-inflammatories, immuno-suppressants and biologics that treat auto-immune disorders. These therapies target symptomatic improvement in the inflammation associated with CD, are widely considered to be of limited efficacy in the long term, and are associated with numerous side effects. This speaks to the great unmet need for an effective therapy for this debilitating disease. Additionally, there is no current therapy that treats the suspected underlying cause of Crohn’s disease. We have developed RHB-104 with the MAP hypothesis in mind, which posits that Crohn's disease is caused by infection by a bacteria, Mycobacterium avium subspecies paratuberculosis (MAP). This is similar to peptic ulcer disease, a condition that was initially associated with stress, smoking, NSAIDs and other behavioral factors, yet was found to be caused by H. pylori bacterial infection in the 1980s, revolutionizing the field of ulcer treatment. Validation of this theory would revolutionize how Crohn's disease is viewed and treated by the medical community and RHB-104 is the only therapy in development targeting MAP infection. 
Author Interviews, HIV, Merck / 02.08.2018

MedicalResearch.com Interview with: merck Kathleen Squires MD Director, Division of Infectious Diseases Jefferson University Hospitals and Ming-Tai Lai, PhD Senior Principal Scientist, Biology Discover Merck   MedicalResearch.com: What is the background for this study? What are the main findings?  Dr. Squires: The DRIVE-FORWARD study is a pivotal, randomized, double-blind, Phase 3 study that evaluated the safety and efficacy of doravirine (DOR), a non-nucleoside reverse transcriptase inhibitor (NNRTI) in treatment-naïve adults with HIV-1 infection. Data from week 48 of this trial have previously been presented demonstrating that doravirine met its primary endpoint of non-inferior efficacy compared to ritonavir-boosted darunavir (DRV+r). In addition, at 48 weeks, a secondary endpoint showed that the doravirine-treated group had statistically significant lower levels of fasting LDL-C and non-HDL-C versus the DRV+r group. The data presented at AIDS 2018 are week 96 data from the DRIVE-FORWARD trial. At week 96, the doravirine group demonstrated efficacy of 73.1% compared with 66.0% in the DRV+r group, a treatment difference of 7.1% (95% CI: 0.5, 13.7)  Two participants in the DOR treatment group developed genotypic and phenotypic resistance to DOR through 96 weeks of treatment. The rate of discontinuation of therapy due to adverse events was 1.6 percent in the DOR group and 3.4 percent in the DRV+r group. Doravirine is a late-stage investigational NNRTI for the treatment of HIV-1 infection in treatment-naïve adults and is being evaluated both as a once-daily single-entity tablet in combination with other antiretroviral agents, and as a once-daily fixed-dose combination regimen with lamivudine (3TC) and tenofovir disoproxil fumarate (TDF). Earlier this year, Merck announced that the FDA accepted for review two New Drug Applications (NDAs) for doravirine for the treatment of HIV-1 infection in treatment-naïve adults. The NDAs are based upon the findings at week 48 of two ongoing Phase 3 trials, DRIVE-FORWARD and DRIVE-AHEAD, evaluating the efficacy and safety of doravirine and the fixed-dose combination regimen of DOR/3TC/TDF, respectively. The FDA has set a target action date of October 23, 2018 for both applications. Dr. Lai: This study aimed to characterize the mutant viruses selected in treatment-naïve participants through week 48 from DRIVE-FORWARD and DRIVE-AHEAD, and to assess the impact of selected mutations on non-nucleoside reverse transcriptase inhibitor (NNRTI) susceptibility and viral fitness. All of the seven doravirine (DOR)-resistant mutants are either partially susceptible or susceptible to etravirine. Mutants containing the F227C substitution were shown to be hypersusceptible to some nucleoside reverse transcriptase inhibitors (NRTIs) such as azidothymidine (AZT), tenofovir (TFV), lamivudine (3TC), and MK-8591. Among the 12 participants who developed efavirenz (EFV) resistance, 9 of the EFV-resistant clinical mutants were susceptible to DOR with fold-change <2.5. The majority of DOR-selected viruses identified in the treatment-naïve participants in clinical trials to date retain susceptibility to etravirine and hypersensitivity to some NRTIs, with low replication capacity. In addition, the majority of EFV-selected viruses retain susceptibility to DOR. 
Author Interviews, Education, Pharmaceutical Companies / 01.08.2018

MedicalResearch.com Interview with: [caption id="attachment_43644" align="alignleft" width="200"]Brian J. Piper, PhD, MS Department of Basic Sciences Geisinger Commonwealth School of Medicine Scranton, PA 18509 Dr. Piper[/caption] Brian J. Piper, PhD, MS Department of Basic Sciences Geisinger Commonwealth School of Medicine Scranton, PA 18509 MedicalResearch.com: What is the background for this study? Response: The authors of this study are biomedical scientists, health care providers and educators who teach medical and pharmacy students. It is a standard practice in reputable medical journals like the New England Journal of Medicine to disclose conflicts of interest (CoI). Reputable sources like the Cochrane Library also disclose CoIs and analyze for their potential impact on the evidence base. Unfortunately, textbooks, which can be highly influential in the training of medical professionals, usually do not disclose their conflicts of interest. A prior study in this quantitative bioethics area found that more than one-quarter of a team-authored pharmacology textbook, Goodman and Gilman’s Pharmacological Basis of Therapeutics, had an undisclosed patent (PLoS One, 2015; 10: e0133261).  The goal of this investigation was to determine whether there were undisclosed CoIs in textbooks used in the training and as a reference for allopathic physicians, osteopathic physicians, dentists, pharmacists, nurses and other allied healthcare providers. 
Abbvie, Author Interviews, OBGYNE, Pain Research / 26.07.2018

MedicalResearch.com Interview with: [caption id="attachment_43518" align="alignleft" width="200"]Dr. Dawn Carlson MD MPH Vice President, General Medicine Development AbbVie  Dr. Carlson[/caption] Dr. Dawn Carlson MD MPH Vice President, General Medicine Development AbbVie  MedicalResearch.com: Please provide some background on this announcement. Would you briefly explain what endometriosis is? Whom does it affect and how does it interfere with quality of life? Response: Endometriosis is one of the most common gynecologic disorders in the U.S that affects an estimated one in 10 women of reproductive age. It occurs when tissue similar to the lining of the uterus starts growing outside of the uterus, where it doesn’t belong. The symptoms of endometriosis, including pain with menstrual periods and between periods, and with sexual intercourse, can be debilitating and significantly impact day-to-day activities of women’s lives, personally and professionally. Unfortunately, women with endometriosis can suffer for up to 10 years and visit multiple physicians before receiving a proper diagnosis. Unresolved endometriosis pain results in higher healthcare costs from emergency department visits and repeat surgeries. 
Author Interviews, Flu - Influenza, Genentech / 26.07.2018

MedicalResearch.com Interview with: [caption id="attachment_43512" align="alignleft" width="200"]Mark Eisner MD MPH Vice President and Global Head of Respiratory Actemra, ID, and Metabolism Clinical Development at Genentech Professor of Clinical Medicine University of California, San Francisco Dr. Mark Eisner[/caption] Mark Eisner MD MPH Mark D. Eisner, MD, MPH Vice President, Product Development Immunology, Infectious Disease, and Ophthalmology Genentech   MedicalResearch.com: What is the background for this study? Would you briefly explain how baloxavir marboxil differs from other flu treatments?  Response: CAPSTONE-2 is a Phase III multicenter, randomized, double-blind study that evaluated a single dose of baloxavir marboxil compared with placebo and oseltamivir in people 12 years and older who are at a high risk of complications from the flu. The high risk inclusion criteria in CAPSTONE-2 were aligned with the Centers for Disease Control and Prevention (CDC), which defines people at high risk for serious flu complications to include adults 65 years of age or older, or those who have conditions such as asthma, chronic lung disease, diabetes or heart disease. For these people, flu can lead to hospitalization or even death. Participants enrolled in the study were randomly assigned to receive a single dose of 40 mg or 80 mg of baloxavir marboxil (according to body weight), placebo or 75 mg of oseltamivir twice a day for five days. The FDA recently accepted a New Drug Application (NDA) and granted Priority Review to baloxavir marboxil as a single-dose, oral treatment for acute, uncomplicated influenza in people 12 years and older. The NDA was based on results from the Phase III CAPSTONE-1 study of a single dose of baloxavir marboxil compared with placebo or oseltamivir 75 mg, twice daily for five days, in otherwise healthy people with the flu. Results from a placebo-controlled Phase II study in otherwise healthy people with the flu were included as supporting data in the NDA. The FDA is expected to make a decision on approval by December 24, 2018. Baloxavir marboxil is a first-in-class, single-dose investigational oral medicine with a novel proposed mechanism of action designed to target the influenza A and B viruses, including oseltamivir-resistant strains and avian strains (H7N9, H5N1). Unlike other currently available antiviral treatments, baloxavir marboxil is the first in a new class of antivirals designed to inhibit the cap-dependent endonuclease protein within the flu virus, which is essential for viral replication. By inhibiting this protein, baloxavir marboxil prevents viral replication earlier in the flu virus life cycle.
Author Interviews, Eli Lilly, Lancet, Pharmacology, Rheumatology, UCLA / 26.07.2018

MedicalResearch.com Interview with: [caption id="attachment_43506" align="alignleft" width="166"]Daniel J. Wallace M.D., FACP, MACR Associate Director, Rheumatology Fellowship Program Board of Governors, Cedars-Sinai Medical Center Professor of Medicine, Cedars-Sinai Medical Center David Geffen School of Medicine Center at UCLA In affiliation with Attune Health  Beverly Hills, Ca 90211 Dr. Wallace[/caption] Daniel J. Wallace M.D., FACP, MACR Associate Director, Rheumatology Fellowship Program Board of Governors, Cedars-Sinai Medical Center Professor of Medicine, Cedars-Sinai Medical Center David Geffen School of Medicine Center at UCLA In affiliation with Attune Health Beverly Hills, Ca 90211 MedicalResearch.com: What is the background for this study? What are the main findings?   Response: This is the first positive study of systemic lupus erythematosus (SLE) using baricitinib,  a small oral molecule that blocks the JAK system. The human kinome consists of 500 genes and helps regulate cell surface receptor interaction. While agents that inhibit certain pathways are approved for rheumatoid arthritis and certain malignancies, this is the first study of its kind in SLE.
Author Interviews, BMJ, Boehringer Ingelheim, McGill, Pharmacology / 19.07.2018

MedicalResearch.com Interview with: [caption id="attachment_43242" align="alignleft" width="133"]Samy Suissa, PhD Director, Centre for Clinical Epidemiology, Lady Davis Institute Professor, Departments of Epidemiology and Biostatistics and of Medicine McGill University Dr. Suissa[/caption] Samy Suissa, PhD Director, Centre for Clinical Epidemiology, Lady Davis Institute Professor, Departments of Epidemiology and Biostatistics and of Medicine McGill University  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Sulfonylureas are widely used oral antidiabetic drugs that are recommended as second-line treatments after first-line metformin to treat patients with type 2 diabetes. While their safety has been studied extensively, studies in patients with poorly controlled diabetes in need of pharmacotherapy escalation have been sparse and limited. Our study evaluated whether adding or switching to sulfonylureas after initiating metformin treatment is associated with increased cardiovascular or hypoglycaemic risks, compared with remaining on metformin monotherapy. Using a large cohort of over 77,000 patients initiating treatment with metformin monotherapy, we found that adding or switching to sulfonylureas is associated with modest increases of 26% in the risk of myocardial infarction and 28% in the risk of death, as well as an over 7-fold major increase in the risk of severe hypoglycaemia leading to hospitalisation. In particular, we found that switching from metformin to sulfonylureas was associated with higher risks of myocardial infarction and death, compared with adding sulfonylureas to metformin. 
Asthma, AstraZeneca, Author Interviews, Immunotherapy, Lancet, Pulmonary Disease / 27.06.2018

MedicalResearch.com Interview with: [caption id="attachment_42814" align="alignleft" width="141"]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 Dr. Panettieri[/caption] 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).
AstraZeneca, Author Interviews, Diabetes / 24.06.2018

MedicalResearch.com Interview with: [caption id="attachment_42698" align="alignleft" width="140"]Chantal Mathieu, MD, PhD Professor of Medicine Clinical and Experimental Endocrinology Catholic University of Leuven, Belgium Dr. Mathieu[/caption] 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).
Author Interviews, BMJ, GSK, Smoking, Tobacco, Tobacco Research / 14.06.2018

MedicalResearch.com Interview with: “Day 1 of nicotine patch, just stuffed my face with lunch at work and do NOT even want a cigarette” by David Bruce Jr. is licensed under CC BY 2.0Paul Aveyard Professor of Behavioural Medicine Nuffield Department of Primary Care Health Sciences University of Oxford Radcliffe Primary Care Building Radcliffe Observatory Quarter Oxford MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Tobacco addiction occurs because of repeated pairings of the act and sensation of smoking with binding of nicotine in the midbrain leading to release of dopamine in the nucleus accumbens. These repeated pairings create associative learning and, when brain nicotine concentrations fall, this produces a compulsion to keep using tobacco. In theory, blocking the actions of nicotine released while smoking ought to reverse this learning. One way to do this is to use a nicotine patch which provides a steady state high concentration of nicotine that desensitises the nicotinic receptors in the midbrain, making them unresponsive to nicotine from a smoked cigarette. This is the theory behind nicotine preloading. The clinical trial evidence that preloading works is equivocal, with some trials suggesting a very large therapeutic effect and others no benefit at all. In the light of both the promise and the uncertainty, we aimed to complete the largest trial to date of nicotine preloading to examine its effectiveness, safety, and tolerability.
Amgen, Author Interviews, Gastrointestinal Disease, Gluten / 07.06.2018

MedicalResearch.com Interview with: [caption id="attachment_42052" align="alignleft" width="135"]Markku Mäki, MD, PhD Professor (emeritus) at the University of Tampere and Presently research director at the Tampere University Hospital Tampere, Finland Prof. Mäki[/caption] Markku Mäki, MD, PhD Professor (emeritus) at the University of Tampere and Presently research director at the Tampere University Hospital Tampere, Finland MedicalResearch.com: What is the background for this study? Response: The only treatment for this life-long gluten-induced autoimmune systemic disease is a strict avoidance of wheat, rye and barley, the food cereals which contain gluten, the environmental trigger and driving force in celiac disease.  Gluten causes intestinal inflammation, usually with (but sometimes without) gastrointestinal or nutritional symptoms or signs, and with frequent extra-intestinal diseases. However, it is impossible for celiac disease patients to avoid gluten entirely and indefinitely and a third of patients report symptoms on a strict gluten-free diet. Gut mucosal healing is not optimal in half of the patients, and inflammation and injury is detected for years after starting the diet, presumably due to contamination with gluten in the diet. This is why patients are requesting, and academia and industry are looking for novel adjunct therapies for celiac disease. Initially, these therapies are tested to prevent the consequences of hidden gluten; the ultimate goal being that also celiacs could one day eat safely wheat, barley and rye products. Some 20 novel experimental therapies are at present actively being investigated (modifying wheat or different drugs, devices and vaccines/immunotherapy). The present study investigated whether blocking interleukin 15, an important mediator of celiac disease, reduces or prevents gluten-driven ill health, both the inflammation and injury at the small intestinal mucosal level and gluten-induced symptoms. The experimental drug used was Amgen’s AMG 714, a human monoclonal antibody, used at a low and high dose, in the presence or absence of a high-dose gluten challenge.
ASCO, Author Interviews, Dermatology, Melanoma, Merck, University of Pittsburgh / 05.06.2018

MedicalResearch.com Interview with: [caption id="attachment_40044" align="alignleft" width="200"]This image depicts the gross appearance of a cutaneous pigmented lesion, which had been diagnosed as superficial spreading malignant melanoma (SSMM). Note the roughened edges of this mole, and its heterogeneous, mottled, multicolored appearance, which are all characteristics that should evoke suspicions about its classification. This image depicts the gross appearance of a cutaneous pigmented lesion, which had been diagnosed as superficial spreading malignant melanoma (SSMM). Note the roughened edges of this mole, and its heterogeneous, mottled, multicolored appearance, which are all characteristics that should evoke suspicions about its classification.
CDC Image[/caption] Dr. Diwakar Davar, MD Assistant Professor of Medicine Division of Hematology/Oncology University of Pittsburgh  MedicalResearch.com: What is the background for this study? What are the main findings? Response: The optimal surveillance strategy to detect recurrence in cutaneous melanoma remains elusive. Risk of recurrence increases with higher stage, and is especially high for patients with stage IIIC disease. Although consensus guidelines agree on surveillance imaging for high-risk (stage IIB-IIIC) MEL, there is no consensus regarding optimal frequency/modality in these patients. NCCN guidelines suggest chest radiography (CXR) at 6- to 12-month intervals for stage IA-IIA melanoma  patients; although this is controversial. There exists a great deal of practice variation in the surveillance of these patients.
Author Interviews, Boehringer Ingelheim, Pulmonary Disease / 05.06.2018

MedicalResearch.com Interview with: [caption id="attachment_42182" align="alignleft" width="143"]Christopher J. Ryerson, M.D. Assistant Professor Centre for Heart Lung Innovation University of British Columbia Vancouver, Canada Dr. Ryerson[/caption] Christopher J. Ryerson, M.D. Assistant Professor Centre for Heart Lung Innovation University of British Columbia Vancouver, Canada MedicalResearch.com: What is the background for this study? What are the main findings? Response: A new Idiopathic pulmonary fibrosis (IPF) mortality analysis presented at the American Thoracic Society’s 2018 annual conference suggests that treatment with nintedanib may be associated with reduced risk of death in patients with the rare lung disease idiopathic pulmonary fibrosis (IPF). Pooled data from the two Phase II INPULSIS trials and the Phase II TOMORROW study compared the number of deaths observed versus the number predicted based on GAP stage over one year. GAP stage is used to predict IPF prognosis and is based on gender, age and lung function (as measured by forced vital capacity [FVC] decline predicted and DLco % predicted). Higher stages of GAP are associated with an increased risk of death. Across the population in the analysis (n=1,228), there were fewer deaths observed in each treatment group than predicted based on GAP stage at baseline (nintedanib: 42 vs. 89.9; placebo: 41 vs. 64.2). In the treated group, the number of observed deaths was 46.7% of the number predicted based on GAP stage, while in the placebo group the number of observed deaths was 63.9% of the number predicted. Based on these observations, the analysis suggests that nintedanib may be associated with a 26.8% relative reduction in the risk of death compared with placebo over one year. 
Author Interviews, Pain Research, Pharmaceutical Companies / 04.06.2018

MedicalResearch.com Interview with: Zosano Pharma Dr. Peter Schmidt, MD, MSc Senior Director, medical Affairs and Clinical Development Zosano Pharma   MedicalResearch.com: What is the background for this study? What are the main findings? Response: This was a post-hoc analysis of Zosano’s pivotal efficacy trial using its adhesive dermally-applied microarray (ADAM) zolmitriptan formulation, M207. The trial found that M207 was effective versus placebo for the co-primary endpoints of pain freedom and most bothersome symptom (MBS) freedom, both at two hours. The MBS endpoint was just ratified as a new endpoint in the FDA’s February 2018 guidance for acute migraine trials. The stated aim of this new endpoint is “…to better align the study outcome with the symptom(s) of primary importance to patients…” This is logical, as a given migraine patient may not experience all four previous symptom endpoints (pain, photophobia, phonophobia, nausea).
Abbvie, ASCO, Author Interviews, Cancer Research, Leukemia / 03.06.2018

MedicalResearch.com Interview with: [caption id="attachment_42144" align="alignleft" width="200"]Dr. Danelle James, Dr. James[/caption] Dr. Danelle James, M.D., M.A.S. Head of Clinical Science Pharmacyclics, an AbbVie Company MedicalResearch.com: What is the background for this study? What are the main findings? Response: CAPTIVATE is a Phase 2 study investigating IMBRUVICA (ibrutinib) plus VENCLEXTA (venetoclax) for the treatment of Chronic Lymphocytic Leukemia (CLL) in the first-line setting. It was designed to evaluate if remission with undetectable minimal residual disease (MRD) can provide treatment-naïve CLL/SLL patients with treatment holidays (a period of time when a patient is able to stop therapy). The study enrolled 164 patients with previously untreated CLL or SLL. In preclinical and ongoing clinical studies, we’ve seen complementary activities with this combination. The combination has also previously shown potential for deeper remissions, as well as potential for lower risk of tumor lysis syndrome with ibrutinib as the lead-in therapy. Early data from CAPTIVATE show promising activity for the combination in this patient population, with 77 percent of the first 30 patients achieving responses with no detectable MRD in the blood after only six cycles of the combination therapy. Approximately nine out of 10 of the first patients achieved undetectable MRD after 12 cycles of combination therapy (which were preceded by three cycles of single agent ibrutinib, for a total of 15 cycles of therapy). Specifically, 86 percent of the first 14 patients achieved undetectable MRD in the marrow and 93 percent in the peripheral blood.
Author Interviews, Pharmaceutical Companies / 31.05.2018

MedicalResearch.com Interview with: “pills” by Dominique Godbout is licensed under CC BY 2.0George P. Ball PhD Operations and Decision Technologies Department Kelley School of Business, Indiana University Bloomington, IN 47405, MedicalResearch.com: What is the background for this study? What are the main findings? Response: We sought to examine how the intense pressure on firms to produce generic drugs more cheaply might influence product quality. We find that the greater proportion of generic drugs a firm manufactures, the more severe product recalls they experience, because of an apparent relaxation of manufacturing quality standards. Additionally, they experience fewer less severe recalls, which may also result from forces of competition. When the opportunity exists to not announce a recall that has high discretion, competition may lead firms to forgo the recall to avoid negative ramifications associated with recalls.
Author Interviews, J&J-Janssen, Prostate, Prostate Cancer, Urology / 30.05.2018

MedicalResearch.com Interview with: [caption id="attachment_42036" align="alignleft" width="132"]Dr. Fred Saad, MD FRCS Full Professor and Chief of Urologic Oncology, CHUM; Medical Director of Interdisciplinary Urologic Oncology Group, CHUM; Department of Surgery/Faculty of Medicine; Institut du cancer de Montréal/CRCHUM Dr. Saad[/caption] Dr. Fred Saad, MD FRCS Full Professor and Chief of Urologic Oncology, CHUM; Medical Director of Interdisciplinary Urologic Oncology Group, CHUM; Department of Surgery/Faculty of Medicine; Institut du cancer de Montréal/CRCHUM MedicalResearch.com: What is the background for this study? What are the main findings? Response: The SPARTAN study was a Phase 3, randomized, double-blind, placebo-controlled, multicenter study that evaluated ERLEADA (apalutamide), a next-generation androgen signaling inhibitor, in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) who had a rapidly rising PSA (PSA doubling time ≤10 months). The post-hoc analysis presented at the American Urological Association (AUA) 2018 annual meeting showed in patients who received the treatment apalutamide while receiving continuous androgen deprivation therapy (ADT) significantly decreased the risk of PSA progression by 94 percent compared with the placebo group.
AstraZeneca, Author Interviews, Kidney Disease, Mineral Metabolism / 24.05.2018

MedicalResearch.com Interview with: [caption id="attachment_41990" align="alignleft" width="186"]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. Dr. Fishbane[/caption] 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.