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.  (more…)
Author Interviews, Education, Pharmaceutical Companies / 01.08.2018

MedicalResearch.com Interview with: 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.  (more…)
Abbvie, Author Interviews, OBGYNE, Pain Research / 26.07.2018

MedicalResearch.com Interview with: 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.  (more…)
Author Interviews, Flu - Influenza, Genentech / 26.07.2018

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Eli Lilly, Lancet, Pharmacology, Rheumatology, UCLA / 26.07.2018

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, BMJ, Boehringer Ingelheim, McGill, Pharmacology / 19.07.2018

MedicalResearch.com Interview with: 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.  (more…)
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…)
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. (more…)
Amgen, Author Interviews, Gastrointestinal Disease, Gluten / 07.06.2018

MedicalResearch.com Interview with: 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. (more…)
ASCO, Author Interviews, Dermatology, Melanoma, Merck, University of Pittsburgh / 05.06.2018

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Boehringer Ingelheim, Pulmonary Disease / 05.06.2018

MedicalResearch.com Interview with: 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.  (more…)
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). (more…)
Abbvie, ASCO, Author Interviews, Cancer Research, Leukemia / 03.06.2018

MedicalResearch.com Interview with: 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. (more…)
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. (more…)
Author Interviews, J&J-Janssen, Prostate, Prostate Cancer, Urology / 30.05.2018

MedicalResearch.com Interview with: 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. (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…)
Author Interviews, Cancer Research, J&J-Janssen, Leukemia / 17.05.2018

MedicalResearch.com Interview with: Andrzej Jakubowiak, MD, PhD Professor of Medicine Director, Myeloma Program University of Chicago MedicalResearch.com: What is the background for this announcement? Would you briefly explain what is meant by multiple myeloma?   Response: DARZALEX (daratumumab) in combination with VELCADE (bortezomib), melphalan and prednisone - VMP - received U.S. FDA approval for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant (ASCT). With this most recent approval, DARZALEX is now the first monoclonal antibody approved for newly diagnosed patients with this disease. Multiple myeloma is an incurable blood cancer that occurs when malignant plasma cells grow uncontrollably in the bone marrow. Despite the introduction of new medicines over the last decade, which has led to significant improvements in outcomes for patients with multiple myeloma, multiple myeloma remains an incurable disease. In 2018, it is estimated that 30,700 people will be diagnosed and 12,770 will die from the disease in the United States. (more…)
Author Interviews, Epilepsy, Neurological Disorders, NYU, Pharmaceutical Companies / 17.05.2018

MedicalResearch.com Interview with: https://www.gwpharm.com/epilepsy-patients-caregivers/patientsAnup Patel, M.D. Section Chief of Neurology Interim Division Chief of Neurology Nationwide Children’s Hospital MedicalResearch.com: What is the background for this study? Response: The study evaluated kids and adults with an epilepsy syndrome (Lennox Gastaut Syndrome – LGS) that is often difficult to treat and does not respond well to current medical treatment.  The study was a double blind randomized control trial evaluating how well a plant based, liquid solution, cannabidiol (CBD) product made by Greenwich Biosciences called Epidiolex helped to treat drop seizures (the most common seizure type in LGS) and how safe it was compared to placebo.  Two doses (10 mg/kg/day and 20 mg/kg/day) were evaluated compared to placebo. (more…)
Addiction, Author Interviews, JAMA, Opiods, Pharmaceutical Companies / 14.05.2018

MedicalResearch.com Interview with: “Big Lunch Extras Reading” by Big Lunch Extras is licensed under CC BY 2.0Scott E. Hadland, MD, MPH, MS Assistant Professor of Pediatrics | Boston University School of Medicine Boston Medical Center Director of Urban Health & Advocacy Track | Boston Combined Residency Program Boston, MA 02118 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Numerous pharmaceutical companies have received media attention for their role in promoting opioid prescribing through speaker programs and other marketing plans in which large-value payments are given to a small number of doctors to promote opioids. In our study, we sought to tell the other side of the story. We wanted to identify whether low-value marketing, including industry-sponsored meals, which are commonplace in the US, were associated with increased opioid prescribing. We found that 1 in 14 doctors received opioid marketing from pharmaceutical companies in 2014, and those that received marketing prescribed 9% more opioids the following year. With each additional meal a doctor received, he or she prescribed more and more opioids the following year. Our sample included 43% of the active physician workforce in the US, suggesting how widespread and far-reaching this effect might be. (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, Infections, Merck / 10.05.2018

MedicalResearch.com Interview with: Dr. Elizabeth Rhee MD Director, Infectious Disease Clinical Research Merck MedicalResearch.com: What is the background for this study? What are the main findings? Response: High-risk patients, such as the critically ill, with suspected bacterial infections require prompt treatment with appropriate empiric therapy to improve survival. Given the high prevalence of multidrug-resistant (MDR) Pseudomonas aeruginosa in the ICU setting, new safe and broadly effective treatment options are needed for critically ill patients requiring antipseudomonal agents. Ceftolozane/tazobactam (C/T) is an antipseudomonal cephalosporin/beta-lactamase inhibitor combination with broad in vitro activity against Gram-negative pathogens, including MDR P. aeruginosa and many extended-spectrum beta-lactamase (ESBL) producers. It is FDA approved for complicated intra-abdominal and urinary tract infections in adults at 1.5g (1g/0.5g) q8h. C/T is currently being studied at 3g (2g/1g) q8h, for the treatment of ventilated nosocomial pneumonia, in the ASPECT-NP Phase 3 trial. This Phase 1 pharmacokinetic (PK) study investigated the penetration of a 3g dose of C/T in the epithelial lining fluid (ELF) of ventilated patients with proven or suspected pneumonia. This is the dose and patient population being evaluated in ASPECT-NP. ELF lines the alveoli, and investigators took samples in a group of 26 patients to see what amount of C/T was in the lung and what was circulating in the plasma during the dosing intervals. In mechanically ventilated critically ill patients, the 3g dose of C/T achieved ≥50% lung penetration (relative to free plasma) and sustained levels in ELF above the target concentrations for the entire dosing interval. These findings support the 3g dose that is included in the ASPECT-NP Phase 3 trial.  (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, Infections, Merck / 10.05.2018

MedicalResearch.com Interview with: Becky Jayakumar, PharmD College of Pharmacy Assistant Professor of Pharmacy Practice Roseman University of Health Sciences MedicalResearch.com: What is the background for this study? What are the main findings? Response: Bacteremia (bloodstream infections) due to Gram-negative (GN) bacteria are a frequent cause of severe sepsis and pose serious therapeutic challenges due to multidrug-resistance (MDR). Ceftolozane/tazobactam (C/T) is a novel antipseudomonal cephalosporin combined with an established β-lactamase inhibitor. This retrospective, observational study evaluated the clinical outcomes of C/T real-world use in severely ill patients. Twenty-two patients with sepsis and/or bacteremia were included; 95% of whom had Pseudomonas aeruginosa that was resistant to almost all antibacterials with the exception of colistin. C/T successfully treated the majority of these complicated patients. In this real-world study, 77% of patients had a clinical response with C/T and 75% had a microbiological response. Clinical success rates were high and mortality rates were similar to other studies in this severely ill population. (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, Infections, Merck / 10.05.2018

MedicalResearch.com Interview with: Amanda Paschke, MD, MSCE Senior principal scientist Infectious disease clinical research Merck Research Laboratories MedicalResearch.com: What is the background for this study? What are the main findings? Response: This study sought to evaluate a new beta-lactam/beta-lactamase inhibitor antibacterial combination, imipenem/relebactam (IMI/REL), compared with colistin plus imipenem for the treatment of infections caused by resistant Gram-negative bacteria. Patients enrolled in the trial had hospital-acquired or ventilator-associated bacterial pneumonia (HABP/VABP), complicated intra-abdominal infections (cIAI), or complicated urinary tract infections (cUTI) caused by pathogens that were non susceptible to imipenem, a carbapenem antibacterial. In this study, the primary outcome was a favorable overall response to treatment, which was comparable between the IMI/REL vs colistin + IMI arms. Colistin (often combined with a carbapenem) is currently among the standard of care treatment regimens for MDR infections.  A key secondary endpoint of the study was safety.  IMI/REL was well tolerated; among all treated patients, drug-related adverse events (AEs) occurred in 16.1% of IMI/REL and 31.3% of colistin + IMI patients with treatment-emergent nephrotoxicity observed in 10% (3/29 patients) and 56% (9/16 patients), respectively (p=0.002). Results of the trial support the use of imipenem-relebactam (IMI/REL) as an efficacious and well-tolerated treatment option for carbapenem-resistant infections.  (more…)
Alzheimer's - Dementia, Author Interviews, Merck, NEJM / 02.05.2018

MedicalResearch.com Interview with: Dr. Michael F. Egan MD Merck & Co. North Wales, PA 19454   MedicalResearch.com: What is the background for this study? What are the main findings? Response: A leading theory of Alzheimer's Disease is that it is caused by the buildup of amyloid plaques in the brain. Amyloid is composed of a sticky peptide called Abeta.  Abeta production can be blocked by Inhibiting an enzyme called BACE.  In animal models, BACE inhibtion prevent amyloid accumulation.  We aimed to see if a potent BACE inhibitor would slow clinical decline in Alzheimer's Disease. EPOCH was a Phase 2/3 randomized, placebo-controlled, parallel-group, double-blind study evaluating efficacy and safety of two oral doses of verubecestat an investigational BACE inhibitor, administered once-daily versus placebo in patients with mild-to-moderate AD currently using standard of care treatment. The primary efficacy outcomes of the study are the change from baseline in cognition (assessed using the Alzheimer's Disease Assessment Scale Cognitive Subscale, or ADAS-Cog),  as well as the change from baseline in function (assessed using the Alzheimer's Disease Cooperative Study – Activities of Daily Living, or ADCS-ADL)  after 78 weeks of treatment. Following the recommendation of the external Data Monitoring Committee (eDMC), which assessed overall benefit/risk during  the trial,  the study was stopped early, as there was “virtually no chance of finding a positive clinical effect.” Verubecestat did not reduce cognitive or functional decline in patients with mild-to moderate Alzheimer’s disease and was associated with treatment-related adverse events.  (more…)
Author Interviews, Cancer Research, Cost of Health Care, JAMA, Pharmaceutical Companies / 09.04.2018

MedicalResearch.com Interview with: Aaron Mitchell, MD Division of Hematology/Oncology, Department of Medicine, Lineberger Comprehensive Cancer Center The Cecil G. Sheps Center for Health Services Research The University of North Carolina at Chapel Hill MedicalResearch.com: What is the background for this study? What are the main findings? Response: Financial relationships between physicians and the pharmaceutical industry are very common. However, we are just beginning to figure out whether these relationships may lead to potentially concerning changes in physician behavior - whether physicians tend to prescribe more of the drugs made by a company that has given them money. We decided to ask whether oncologists who receive money from drugmakers are more likely to use the cancer drugs made by companies that have given them money in the past. In studying two specific groups of cancer drugs, one for kidney cancer and one for chronic myeloid leukemia (CML), we found that oncologists who had received payments such as meals, consulting fees, travel & lodging expenses from the manufacturer of one of these drugs tended to use that drug more. When looking at oncologists who received payments for research, we found increased prescribing among the kidney cancer drugs but not the CML drugs. (more…)
Allergan, Author Interviews, Bipolar Disorder, Depression, Mental Health Research / 05.04.2018

MedicalResearch.com Interview with: Dr. C. David Nicholson, PhD Chief R&D Officer Allergan MedicalResearch.com: What is the background for this data milestone?  Response: Bipolar I depression refers to the depressive episodes of bipolar I disorder, the overarching brain and behavioral disorder. People with bipolar I disorder can have manic and depressive episodes, as well as mixed episodes that feature both manic and depressive symptoms at the same time. Bipolar I depression typically lasts at least two weeks, and can be difficult to differentiate from major depression during diagnosis. Once diagnosed, treating bipolar depression can be difficult given the few therapies available to manage these symptoms of bipolar I disorder. Additionally, patients with bipolar disorder may experience shifts from depression to mania or mania to depression as well as mixed states. More treatment options are needed so that physicians can find a therapy that will treat bipolar depression effectively, while also addressing the myriad of other symptoms that patients can experience. Cariprazine is already approved for the treatment of mania and mixed episodes. With this new data, we have the potential to also treat bipolar depression, effectively addressing the full spectrum of symptoms associated with bipolar I disorder with just one medication. (more…)
Addiction, Author Interviews, Opiods, Pharmaceutical Companies / 04.04.2018

MedicalResearch.com Interview with: http://usworldmeds.com/Mark Pirner, MD, PhD Senior Medical Director US WorldMeds   MedicalResearch.com: What is the background for this study? Would you briefly explain how lofexidine works? Response: LUCEMYRA (lofexidine) was studied in two phase 3 pivotal randomized, double-blind, placebo-controlled clinical studies, and a phase 3 open-label study. Clinical pharmacology studies included evaluation of drug-drug interaction studies that demonstrated lofexidine can be safely administered concomitantly with methadone, buprenorphine or naltrexone. LUCEMYRA is an alpha 2 adrenergic receptor agonist that reduces the surge of norepinephrine signaling in the brain which results from abrupt opioid withdrawal, and thereby reduces the severity of opioid withdrawal symptoms.  (more…)
Author Interviews, Boehringer Ingelheim, FDA, Pulmonary Disease, Rheumatology / 03.04.2018

MedicalResearch.com Interview with: Dr. Thomas Leonard, Ph.D. Executive director, Clinical Development and Medical Affairs, Specialty Care Boehringer Ingelheim MedicalResearch.com: What is the background for this announcement? Would you briefly explain what is meant by systemic sclerosis? What are the disease symptoms and manifestations? Response: The FDA recently granted Fast Track designation to nintedanib for the treatment of systemic sclerosis with interstitial lung disease (SSc-ILD) – paving the way for Boehringer Ingelheim to take an important step in advancing this potential therapy for those affected by this disease. The designation was based on Boehringer Ingelheim’s Investigational New Drug application (IND) and the anticipated efficacy and safety data from SENSCIS™ (Safety and Efficacy of Nintedanib in Systemic SClerosIS), a double-blind, randomized, placebo-controlled global Phase III trial which is fully enrolled and includes more than 520 patients from 32 countries. The FDA’s Fast Track designation facilitates the development of new therapies that treat serious conditions and fulfill an unmet medical need in an effort to get treatments to those in need sooner, like those living with systemic sclerosis. Systemic sclerosis, also known as scleroderma, is a rare disease characterized by thickening and scarring of connective tissue of multiple organs in the body, typically affecting women between ages 25 and 55. Most people with the disease will develop some degree of lung scarring, or interstitial lung disease (ILD), which is the leading cause of death among people with systemic sclerosis. Nintedanib, currently marketed as Ofev®, is approved for treatment of a rare lung disease called idiopathic pulmonary fibrosis, or IPF, and has been shown to slow disease progression as measured by annual rate of decline in lung function. Because SSc-ILD and IPF share similarities in how the underlying lung scarring, or fibrosis, forms in people with the disease, Boehringer Ingelheim is evaluating the impact of nintedanib on SSc-ILD. (more…)
Author Interviews, Breast Cancer, Chemotherapy, JAMA, Novartis / 26.03.2018

MedicalResearch.com Interview with: Melanie E. Royce, MD, PhD Division of Hematology/Oncology University of New Mexico Comprehensive Cancer Center Albuquerque MedicalResearch.com: What is the background for this study? What are the main findings? Response: BOLERO-4 is an open label, single-arm, Phase II study that evaluates the combination of everolimus plus letrozole as a first-line treatment for hormone receptor (HR)-positive/human epidermal growth factor receptor (HER2)-negative advanced breast cancer patients, as well as the use of everolimus plus exemestane beyond initial progression. Results of the BOLERO-4 trial published in JAMA Oncology showed that everolimus in combination with endocrine therapy is an effective first-line treatment option for postmenopausal women with HR+/HER2- advanced breast cancer. A total of 202 patients received everolimus in combination with letrozole as first-line treatment between March 7, 2013 and December 17, 2014. Median progression-free survival (PFS) in the first-line setting was 22.0 months (95% CI 18.1-25.1) with an overall response rate of 45% (95% CI 38.1-52.2) and clinical benefit rate of 74% (95% CI 67.7-80.1). A total of 152 (75%) discontinued treatment, primarily due to disease progression (51%) or adverse events (16%). Data from a smaller number of patients in BOLERO-4 also show limited efficacy with continued everolimus, combined with exemestane, following disease progression. Second-line treatment was ongoing in 16 (32%) patients, while 34 (68%) had discontinued. The most frequent reason for second-line treatment discontinuation was disease progression (56%). In the second-line setting, median PFS was 3.7 months (95% CI 1.9-7.4) with an overall response of 6% (95% CI 1.3-16.5) and clinical benefit rate of 28% (95% CI 16.2-42.5). Safety findings from BOLERO-4 are consistent with previous studies of Afinitor in advanced breast cancer. The most common (≥ 20% incidence) first-line all-grade adverse events were stomatitis (69%), weight loss (44%), nausea (37%) and anemia (35%). Most were ‘low grade’ in severity (grade 1 or 2) and generally well managed. Safety findings show the most common (≥ 10% incidence) second-line adverse events were stomatitis (20%) and weight loss (20%). Lower rates of stomatitis in second-line were noted.  (more…)
Abuse and Neglect, Author Interviews, Neurology, Pharmaceutical Companies / 23.03.2018

MedicalResearch.com Interview with: Dr. Joseph Horrigan MD Pediatric neuropsychiatrist Chief medical officer   MedicalResearch.com: What is the background for this study? Would you briefly explain what is meant by myotonic dystrophy? What are the manifestations of this disease? Response: This was the first pharmaceutical intervention study conducted in adolescents and adults with congenital and juvenile onset DM1. Myotonic dystrophy type 1 (DM1) is a disorder that impacts multiple body systems following a trinucleotide expansion repeat of the DMPK gene on chromosome 19. Children with Congenital DM1 present at birth with respiratory insufficiency, talipes equinovarus (clubfoot), feeding difficulties and hypotonia. There is a risk mortality rate in the first year of life. As children grow, they are at risk for intellectual impairment, autistic features, gastrointestinal symptoms, motor delay and a variety of muscle-based symptoms. (more…)