Asthma, Author Interviews, NEJM, Pediatrics, Pulmonary Disease, Vanderbilt / 08.12.2021

MedicalResearch.com Interview with: Leonard B. Bacharier, MD Janie Robinson and John Moore Lee Chair in Pediatrics Professor of Pediatrics Director - Center for Pediatric Asthma Research Scientific Director - Center for Clinical and Translational Research Section Chief - Pediatric Allergy and Immunology Division of Allergy, Immunology and Pulmonary Medicine Monroe Carell Jr. Children’s Hospital at Vanderbilt University Medical Center  MedicalResearch.com: What is the background for this study?  Is Dupilumab used for other atopic conditions, ie eczema/atopic dermatitis?   Response: Many children with moderate-severe asthma continue to experience asthma exacerbations and poor asthma control despite use of controller therapies.  Dupilumab has been shown to reduce asthma exacerbations in adolescents and adults, as well as to improve atopic dermatitis in children and adults. (more…)
Author Interviews, Dermatology / 05.04.2021

MedicalResearch.com Interview with: Wolfgang Liedtke, M.D., Ph.D. Professor (tenured) of Neurology, Anesthesiology and Neurobiology
Attending Physician, Duke Neurology Clinics for Headache, Head-Pain and Trigeminal Sensory Disorders
Attending Physician, Duke Clinics for Innovative Pain Therapy at Brier Creek (Dept of Anesthesiology)
Duke University School of Medicine, Center for Translational Neuroscience
Durham NC 27710 Since April 2021 Chair of Neurology Global Development Scientific Council Regeneron Pharmaceuticals Tarrytown NY 10591 MedicalResearch.com: What is the background for this study? Response: There are systemic diseases that are characterized by intense itching, yet without inflammation of the skin and not associated with allergic inflammation. For example and importantly, liver disease with non-functional secretion of bile (cholestatic liver disease, most common primary biliary cholangitis, an autoimmune disease), but also chronic end-stage renal disease (also certain lymphomas and pruritic psoriasis where the itch is whole-body, not only restricted to diseased skin). We thought that these diseases might be great starting points to better understand itch because there is no inflamed skin and no allergies. Thus, there must be some systemic factor that causes itch, and we were intent on discovering such factors, and with them, molecular mechanisms how they cause itch. For cholestatic liver disease, one of the best candidates to fit this profile has been lysophosphatidic acid (LPA), since the pioneering discoveries of Andreas Kremer, one of our co-authors. My research laboratory at Duke has been rooted in my discovery of TRPV4 ion channels 20 years ago, out of the Friedman Lab at The Rockefeller University in NYC. Over the years, with my colleague Yong Chen out of my lab, now leading his own independent research operation, we focused on the role of TRPV4 ion channels in skin. 5 years ago Yong and I published a paper that provided some evidence for TRPV4 in skin perhaps playing a role in itch. Working with phospholipids, we made the serendipitous discovery that lysophosphatidyl choline (LPC) is a more potent itch-inducing lipid molecule than LPA. Of note, LPC is the metabolic precursor of LPA. We then found that LPA does not depend on TRPV4 to elicit itch. The more robust itch evoked by LPC was significantly reduced when we knocked down TRPV4 in skin keratinocytes. Itch was NOT affected when TRPV4 was deleted from sensory nerve cells that innervate the skin. In terms of background, my long-term goal has been to elucidate how innervating peripheral nerve cell and innervated organ, such as skin, talk to one another so that the sensation that is felt is regulated or modulated, e.g how can skin influence itch or pain, how can joint cells influence pain. That became the exciting bedrock of our study, and we took it from there, 5 years of hard work with collaborations spanning the globe, and a final stretch of exhausting work during the pandemic. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Cancer Research, Immunotherapy, Pharmaceutical Companies / 22.02.2021

MedicalResearch.com Interview with: https://www.inovio.com/Jeffrey Skolnik, MD Senior Vice President, Clinical Development INOVIO MedicalResearch.com: What is the background for this technology? Would you tell us a little about the brain tumor, Glioblastoma Multiforme? How common is it, whom does it primarily affect?  Response: Glioblastoma (GBM) is the most common malignant brain tumor, affecting more than 10 thousand people each year in the United States. Most people diagnosed with GBM are above the age of 60 years, although GBM can be diagnosed at any age, including in children and young adults. Despite decades of research, GBM remains almost universally fatal. GBM is a tumor of the glial cells of the brain, and current therapies are directed at removing tumor with surgery and killing residual tumor cells with radiation and chemotherapy. More recently, with the introduction of immunotherapies such as immune checkpoint inhibitors (ICI) for the treatment of cancer, clinical studies have tried to add this promising technology to the treatment of GBM. Unfortunately, despite success in other types of cancer, ICIs have not demonstrated any clinical benefit in treating GBM. Newer clinical studies aim at introducing a combination of newer therapies together to try to tackle this terrible disease, and INOVIO’s GBM-001 study is one such example of an innovative approach to treating GBM.    (more…)
Author Interviews, Lipids, Regeneron / 26.08.2020

MedicalResearch.com Interview with: Professor F. J. Raal, FRCP, FCP(SA), Cert Endo, MMED, PhD Director, Carbohydrate & Lipid Metabolism Research Unit Professor & Head, Division of Endocrinology & Metabolism, Faculty of Health Sciences, University of the Witwatersrand  MedicalResearch.com: What is the background for this study? Response: The objective of this randomized phase 3 study was to evaluate the efficacy and safety of evinacumab in adult patients with homozygous familial hypercholesterolemia (HoFH), a condition that remains very difficult to treat. The primary endpoint was reduction of low-density lipoprotein cholesterol (LDL-C) from baseline with evinacumab compared to placebo at 24 weeks.  MedicalResearch.com: Would you briefly explain what is meant by homozygous familial hypercholesterolemia? How many individuals may be affected by this disorder? Response: HoFH, or homozygous familial hypercholesterolemia, is the most serious and more rare form of familial hypercholesterolemia (FH).  It is estimated that as many as 1 in 300,000 people worldwide and approximately 1,300 people in the U.S. are affected by HoFH. A person who has HoFH has inherited two FH genes, one from each parent. They therefore have LDL-C levels that are elevated 4-fold or greater from birth and are at high risk for premature atherosclerotic disease and cardiac events which can occur in childhood. While current treatment guidelines recommend early and intensive LDL-C lowering, people with HoFH tend to be less responsive (or unresponsive) to standard lipid-lowering therapies, including high-intensity statins and PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors and often require lipid apheresis. (more…)
Author Interviews, Dermatology, Regeneron / 23.06.2020

MedicalResearch.com Interview with: Brad Shumel, MD Senior Director of Medical Affairs, Immunology Regeneron MedicalResearch.com: What is the background for this study? Response: Atopic dermatitis is a chronic inflammatory disease and one of the most common skin disorders in children. Severe atopic dermatitis is characterized by skin lesions that often cover a large body surface area and can include intense, persistent itch. Uncontrolled moderate-to-severe atopic dermatitis can have a physical, emotional and psychosocial impact on children, resulting in sleep deprivation, activity restriction, poor school performance, depression and anxiety that can have a greater impact on quality-of-life. The standard of care for this pediatric population has been topical corticosteroids. Children with severe atopic dermatitis who remain uncontrolled with topical therapies have limited treatment options. This Phase 3 trial was conducted to evaluate the safety and efficacy of dupilumab plus topical corticosteroids (TCS) compared with TCS alone in children with uncontrolled severe atopic dermatitis across two treatment arms – every four weeks and every two weeks (Q4W and Q2W). (more…)
Author Interviews, Dermatology, Pediatrics, Pharmaceutical Companies, Regeneron / 15.06.2020

MedicalResearch.com Interview with: Amy S Paller, MD Chair, Department of Dermatology Director, Skin Biology and Diseases Resource-Based Center Walter J. Hamlin Professor of Dermatology Professor of Dermatology and Pediatrics (Dermatology) Feinberg School of Medicine Northwestern University  Dr. Paller discusses the FDA approval of Dupixent® (dupilumab) for children aged 6 to 11 years with moderate-to-severe atopic dermatitis (eczema), whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.  MedicalResearch.com: What is the background for this announcement? Would you briefly discuss what is meant by atopic dermatitis and how it affects children? Response: “Atopic dermatitis, the most common form of eczema, is a chronic inflammatory disease that often appears as a rash on the skin. Moderate-to-severe atopic dermatitis is characterized by rashes that can potentially cover much of the body and can include intense, persistent itching, skin lesions and skin dryness, cracking, redness or darkness, crusting and oozing. Itch is one of the most burdensome symptoms for patients and can be debilitating. This recent FDA approval expands the use of Dupilumab in the U.S. to include children aged 6 to 11 years with uncontrolled moderate-to-severe atopic dermatitis, making it the only biologic medicine approved for this use in this population. Dupilumab is also approved in the U.S. to treat patients aged 12 years and older with moderate-to-severe atopic dermatitis. Moderate-to-severe atopic dermatitis can place a particularly substantial burden on young children aged 6 to 11 years and their families. Limited treatment options leave many of these children to cope with intense, unrelenting itch and skin lesions. Families of these children can spend countless hours helping them to manage their disease.” (more…)
Author Interviews, Dermatology / 25.10.2019

MedicalResearch.com Interview with: Dr. Stephan Weidinger, MD, MaHM Professor of Dermatology Christian-Albrechts-Universit Kiel  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Relatively little is known about the epidemiology and burden of Atopic Dermatitis (AD) in children, adolescents and adults, however, there is increasing evidence that the disease is highly prevalent also in these age groups. Further, very little is known about the disease severity strata. Severity, however, largely defines treatment needs. The EPI-CARE (EPIdemiology of Children with Atopic dermatitis Reporting on their Experience) study was a cross-sectional web-based study of the prevalence and burden of AD in both children and adolescents. It was performed globally across Europe, North America (US, Canada), Latin America (Argentina, Brazil, Colombia, Mexico), Asia (Japan, Taiwan), the Middle East (Israel, Kingdom of Saudi Arabia, Turkey, the United Arab Emirates) and Russia, and used very stringent definitions of AD and the same methodology across age groups. We first analyzed the adolescent data, and it turned out that the prevalence of active Atopic Dermatitis is higher than expected, ranging from 9.29% in the US and 14.7% in Europe. Of note, almost 50% of the adolescents with current AD reported an overall moderate to severe disease activity, and the majority reported a multidimensional burden that includes not only the skin symptoms associated with AD, but also sleep disturbances, symptoms of anxiety/depression, and reductions in quality‐of‐life and productivity. Adolescents also reported a high burden of coexisting atopic diseases that increased with AD severity – 68.6% of those with moderate AD and 81% of those with severe AD reported at least one coexisting atopic disease. atopic dermatitis substantially affects the life of patients and their families, and this burden is higher with greater AD severity. (more…)
Author Interviews, Diabetes, Ophthalmology, Regeneron / 17.05.2019

MedicalResearch.com Interview with: Robert L. Vitti, MD, MBA Vice President and Head, Ophthalmology Regeneron Pharmaceuticals Dr. Vitti discusses the recent announcement that the FDA has approved EYLEA to treat all stages of diabetic retinopathy. MedicalResearch.com: Can you provide additional background on this approval? Would you briefly explain diabetic retinopathy and it's impact on patients? Response: The FDA has approved EYLEA (aflibercept) Injection to treat all stages of diabetic retinopathy (DR). DR is the leading cause of blindness among working-aged American adults. Approximately 8 million people live with DR, a complication of diabetes characterized by damage to the blood vessels in the retina (per 2010 data). The disease generally starts as non-proliferative diabetic retinopathy (NPDR) and often has no warning signs or symptoms. Over time, NPDR often progresses to proliferative diabetic retinopathy (PDR), a stage in which abnormal blood vessels grow on the surface of the retina and into the vitreous cavity, potentially causing severe vision loss. (more…)
Asthma, Author Interviews, FDA, Regeneron / 31.10.2018

MedicalResearch.com Interview with: RegeneronNeil Graham,  M.B.B.S., M.D., M.P.H VP of Immunology & Inflammation Regeneron MedicalResearch.com: What is the background for this announcement?  Response: Patients with moderate-to-severe asthma often have uncontrolled, persistent symptoms despite standard-of-care therapy that may make them suitable for treatment with a biologic therapy. They live with coughing, wheezing and difficulty breathing, and are at risk of severe asthma attacks that may require emergency room visits or hospitalizations. [i],[ii] Oral corticosteroids can provide relief for severe, short-term symptoms. However, their chronic use is limited to the most severe patients due to the potential for serious side effects. [iii],[iv] A particular type of inflammation contributes to the cause of uncontrolled symptoms in multiple inflammatory diseases such as asthma and atopic dermatitis.[v] Dupixent is a medicine that inhibits the overactive signaling of interleukin-4 (IL-4) and interleukin-13 (IL-13), two key proteins that contribute to this type of inflammation. This inhibits cytokine-induced inflammatory responses, including the release of proinflammatory cytokines, chemokines, nitric oxide, and IgE; however, the mechanism of action of Dupixent in asthma has not been definitively established. (more…)
Author Interviews, Lipids, Sanofi / 29.11.2017

MedicalResearch.com Interview with: Dr. Jay Edelberg MD, PhD VP Head of CV Development and Head Global CV Medical Affairs Sanofi MedicalResearch.com: What is the background for this study? What are the main findings? Response: Clinical trials of lipid-lowering therapies (LLTs), including statins, often report variations in treatment response regarding effects on low density-lipoprotein cholesterol (LDL-C) levels, although LDL-C reductions are fairly consistent between trials. Praluent is generally well tolerated, however hyporesponsiveness exists in few patients. Potential causes for variation in patient responsiveness to Praluent include lack of receipt of active study drug, changes in concurrent LLTs, inaccurate or unrepresentative baseline lipid levels, concurrent acute-phase illness, and biological nonresponsiveness. This analysis evaluated patients pooled from 10 ODYSSEY trials to assess characteristics of patients with hyporesponsiveness to Praluent, defined as <15% LDL-C reduction from baseline at all analyzed time points. Overall, only 1% of patients (n=33) had <15% LDL-C reduction at all time points. Prolonged hyporesponsiveness to Praluent was rarely associated with Praluent antidrug antibodies. Of the 33 patients with <15% LDL-C reduction at all study timepoints, 27 had undetectable or missing alirocumab levels, absence of pharmacokinetics analyses, or early treatment discontinuation. (more…)