Author Interviews, Hematology / 25.06.2020
Real World Study of Rixubis in Patients with Hemophilia B
MedicalResearch.com Interview with:
Dr. med. Wolfhard Erdlenbruch, M.D.
Vice President
Head of Global Medical Affairs Hematology
MedicalResearch.com: What is the background for this study?
[caption id="attachment_54704" align="alignleft" width="156"]
Dr. Erdlenbruch[/caption]
Response: At the World Federation of Hemophilia Virtual Summit 2020 (WFH 2020), results were presented from a real-world, post-marketing surveillance study aimed to evaluate the safety and effectiveness of RIXUBIS® in adult and pediatric patients with hemophilia B in South Korea, entitled “Safety and Effectiveness of Rixubis in Patients with Hemophilia B in South Korea: A Real-World, Prospective, Post-marketing Surveillance Study”.
Data from the study demonstrate the safety and efficacy profile of RIXUBIS® for treatment of bleeds, perioperative/surgery, and prophylaxis in adult and pediatric patients with hemophilia B in the real-world setting in South Korea. The study showed that 86.6% (123/142) of hemostatic effectiveness assessments for RIXUBIS® were reported as good or excellent, and of the 11 adverse events reported, all were mild in severity, with 10 resolved/recovered events not related to RIXUBIS®, and one event (inhibitory antibody development) unconfirmed.1
RIXUBIS® [Nonacog gamma, recombinant FIX concentrate] is a recombinant coagulation factor IX product, indicated for the control and prevention of bleeding episodes in patients with hemophilia B.
Dr. med. Wolfhard Erdlenbruch, M.D.
Vice President
Head of Global Medical Affairs Hematology
MedicalResearch.com: What is the background for this study?
[caption id="attachment_54704" align="alignleft" width="156"] Dr. Erdlenbruch[/caption]
Response: At the World Federation of Hemophilia Virtual Summit 2020 (WFH 2020), results were presented from a real-world, post-marketing surveillance study aimed to evaluate the safety and effectiveness of RIXUBIS® in adult and pediatric patients with hemophilia B in South Korea, entitled “Safety and Effectiveness of Rixubis in Patients with Hemophilia B in South Korea: A Real-World, Prospective, Post-marketing Surveillance Study”.
Data from the study demonstrate the safety and efficacy profile of RIXUBIS® for treatment of bleeds, perioperative/surgery, and prophylaxis in adult and pediatric patients with hemophilia B in the real-world setting in South Korea. The study showed that 86.6% (123/142) of hemostatic effectiveness assessments for RIXUBIS® were reported as good or excellent, and of the 11 adverse events reported, all were mild in severity, with 10 resolved/recovered events not related to RIXUBIS®, and one event (inhibitory antibody development) unconfirmed.1
RIXUBIS® [Nonacog gamma, recombinant FIX concentrate] is a recombinant coagulation factor IX product, indicated for the control and prevention of bleeding episodes in patients with hemophilia B.
Dr. Shumel[/caption]
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).
Dr. Yosipovitch[/caption]
Gil Yosipovitch, MD, Professor
Miami Itch Center
Lennar Medical Foundation
South Miami Clinic in Coral Gables
University of Miami Health System
MedicalResearch.com: What is the background for this study?
Response: Chronic Pruritus is a common and burdensome condition in patients with end stage chronic kidney disease (CKD). It is Present at all stages of CKD, not only in patients undergoing hemodialysis (including stage 3-5 CKD). There are no approved treatments for this condition in US and Europe. CKD pruritus has significant impact on quality of life of patients with higher mortality rates due to its effect on sleep.
Studies in the last 2 decades have shown that in patients with CKD pruritus there is an imbalance between endogenous mu opioids that are over expressed to Kappa Opioids that are down regulated.
Difelikefalin (DFK) is a novel peripherally selective kappa opioid receptor (KOR) agonist. Study of IV DFK administration in hemodialysis patients has recently been published and showed significant anti Pruritic effect ( NEJM Fishbane et al. 382: 289-290, 2020).
Dr. Factor[/caption]
Stewart A. Factor, D.O.
Professor of Neurology
Director of the Movement Disorders Program
Vance Lanier Chair of Neurology
Emory University School of Medicine
MedicalResearch.com: What is the background for this study? Would you briefly explain what is meant by OFF episodes.
Response: Parkinson’s disease (PD) is a chronic, progressive neurodegenerative disease characterized by motor symptoms, including tremor at rest, rigidity and impaired movement, as well as significant non-motor symptoms, such as cognitive impairment, psychiatric symptoms and autonomic symptoms (i.e. urinary issues, constipation, low blood pressure). It is the second-most common neurodegenerative disease after Alzheimer’s disease and it is predicted that the prevalence of Parkinson’s disease will double by the year 2040. The symptoms of PD are in substantial part, due to loss of dopamine nerve cells in the brain. The current standard of care for PD includes replacing the dopamine loss by the use of oral carbidopa/levodopa. Levodopa is a precursor of dopamine, converted in the brain.
OFF episodes have been a significant unmet need in Parkinson’s disease since the emergence of levodopa. Initially, levodopa controls PD symptoms in a continuous fashion throughout the day. With time the response becomes less predictable and patients experience a re-emergence or worsening of PD symptoms. These episodes are what we mean by OFF episodes. OFF episodes can be characterized, in part, by re-emergence of motor symptoms including tremor, stiffness or slowed movement that can happen at any point during the day. OFF episodes typically begin within the first five years of treatment and occur at the end of a dose. This is referred to as end of dose failure or wearing off. Within the first four to six years after diagnosis, regardless of disease severity, up to 60 percent of people with PD experience OFF episodes. With time these episodes become longer, more severe and disabling, more frequent and less predictable as PD progresses. They can take up more than half the day
OFF episodes may alter a persons’ ability to perform everyday activities by slowing or even precluding their completion. The result is significant burden and distress for people living with Parkinson’s disease (PD) and their care partners.
CTH-300 was a Phase 3, 12-week, randomized, double-blind, placebo-controlled, parallel group, study examining the efficacy, safety and tolerability of apomorphine hydrochloride sublingual film (KYNMOBI) in people with levodopa-responsive PD complicated by OFF episodes. The primary endpoint was a mean change in the score from pre-dose in the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Motor Examination at 30 minutes after dosing at the 12-week visit of the maintenance treatment phase. The key secondary endpoint was the percentage of people with PD with a patient-rated full ON (or best) response within 30 minutes at the 12-week visit of the maintenance treatment phase.
Dr. Desai[/caption]
Nimesh D. Desai, MD, PhD
Director, Thoracic Aortic Surgery Research Program
Associate Professor of Surgery
Hospital of the University of Pennsylvania
MedicalResearch.com: What is the background for this study?
Dr. Chase Brown: Opioid use in the United States is a public health emergency. We know that opioids prescribed after general surgery operations to patients who never received them within the year prior to their surgery are at increased risk for continuing to take opioids months later. However, this has not been studied in patients undergoing cardiac surgery, who often times have more severe post-operative pain.
Our goal in this study was to determine how many patients after cardiac surgery and are opioid naive are continuing to take opioids within 90-180 days after their surgery. 
Dr. Vandrey[/caption]
Ryan Vandrey, Ph.D.
Associate Professor
Behavioral Pharmacology Research Unit
Johns Hopkins University School of Medicine
Baltimore, MD 21224
MedicalResearch.com: What is the background for this study?
Response: The background for this study is that 33 states in the U.S. have legalized medicinal cannabis use and millions of people are using cannabis for therapeutic purposes, but we have very little data on the broad health impacts of medicinal cannabis use.
We surveyed medicinal cannabis users and non-using controls who had a variety of health problems and found that the cannabis users reported better health, quality of life, and less healthcare utilization compared with controls. Because we worried about group characteristics accounting for the differences observed, we then did an analysis of people who switched groups over time (e.g. non-users who later initiated cannabis use or cannabis users who later quit) and found the same differences emerged in the same individuals over time. Important to note here is that not all individuals who used cannabis benefited from it and that most participants were using high CBD varieties of cannabis in conjunction with more traditional treatments.
Dr. Hänggi[/caption]
MedicalResearch.com: What is the background for this study?
Response: Anti-MAG neuropathy is a rare form of acquired demyelinating neuropathy. The disease onset normally presents after the age of 50 years and is 2.7 times more frequent in men than in women, with a prevalence of about 1 in 100,000. It is caused by the production of monoclonal anti-MAG IgM antibodies that recognize the HNK-1 epitope. The myelin-associated glycoprotein MAG is a mediator for the formation and maintenance of the myelin sheaths. There is strong evidence that the binding and deposition of anti-MAG IgM autoantibodies on myelin sheath is responsible for the demyelination, which clinically manifests itself as a peripheral neuropathy affecting primarily sensory nerves. However, the causes and the exact mechanisms behind the expansion of anti-MAG IgM producing B-cell and plasma cell clones are not fully understood.
Most off-label treatments aim to reduce pathogenic autoantibody titers by depleting autoantibody-producing B cell clones which interfere with antibody-effector mechanisms, or physically remove autoantibodies from the circulation. Most frequently, the anti-CD20 monoclonal antibody rituximab is used to treat anti-MAG neuropathy patients. However, all of these treatment options often lack of selectivity, efficiency, or can induce severe adverse effects in some patients.
Polyneuron has designed PN-1007 to highly selectively target the IgM autoantibodies that cause anti-MAG neuropathy. PN-1007 is a glycopolymer that mimics the natural HNK-1 carbohydrate epitope found on myelin of peripheral nerves and binds to the circulating disease-causing antibodies. By eliminating these pathogenic antibodies, PN-1007 may protect the integrity of the neuronal myelin sheaths of anti-MAG neuropathy patients.
Dr. Al-Hendy[/caption]
MedicalResearch.com: What is the background for this approval?
Uterine fibroids, commonly referred to as uterine leiomyomas, are the most common type of non-cancerous tumor known to impact women of reproductive age (30-50 years old). In fact, studies show that uterine fibroids can occur in up to 70 percent of European American women and over 80 percent of African American women by age 50. As a result of uterine fibroids, women can experience a range of symptoms, the most common being heavy menstrual bleeding (i.e. prolonged and/or frequent bleeding), which can lead to other health effects such as anemia, fatigue, pelvic pain, urinary frequency etc.
Uterine fibroid treatment recommendations have historically been based on the size and location of the fibroid(s). When treating larger and more complicated fibroids, healthcare providers have typically believed that surgery is their best course of action, which has made uterine fibroids the leading reason for the hysterectomies performed in the U.S. The FDA approval of ORIAHNN was based on improving care for uterine fibroid sufferers who have had a negative impact on their quality of life due to disruptive symptoms. What makes the approval of ORIAHNN so exciting, is that women now have an oral therapy to directly address heavy menstrual bleeding due to uterine fibroids.
Dr. Kempe[/caption]
Allison Kempe, MD, MPH
Ergen Family Endowed Chair in Pediatric Outcomes Research
Professor of Pediatrics, University of Colorado School of Medicine
Director of ACCORDS (Adult and Child Consortium for Health Outcomes Research and Delivery Science)
University of Colorado School of Medicine | Children’s Hospital Colorado
MedicalResearch.com: What is the background for this study?
Response: In 2019 the WHO designated vaccine hesitancy as one of the ten leading threats to global health. Although studies have assessed parental vaccine hesitancy in different localities and estimated vaccine refusals nationally, there is little recent US national data on the prevalence of hesitancy about routine childhood vaccines and national hesitancy rates for influenza vaccine have never been assessed. We used a hesitancy scale developed by the WHO to estimate levels of parental hesitancy for both routine childhood and childhood influenza vaccination 
Dr. Crowley[/caption]
Matthew J. Crowley, MD
Core Investigator, Durham Center of Innovation to Accelerate Discovery and Practice Transformation (ADAPT)
Affiliated Investigator, VA Office of Rural Health
Staff Physician, Endocrinology Section, Durham VA Health Care System
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Dr. Paller[/caption]
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.”
Dr. Blume[/caption]
Dr. Christine Blume PhD
Centre for Chronobiology
Psychiatric Hospital of the University of Basel
Transfaculty Research Platform Molecular and Cognitive Neurosciences
Basel
MedicalResearch.com: What is the background for this study?
Response: In modern societies, human rest-activity rhythms and sleep are between the often-conflicting poles of external social time (e.g., work hours and leisure activities) and an individual’s internal biological time. This can lead to so-called “social jetlag”, which has repeatedly been associated with detrimental health effects. With the restrictions to control the pandemic, social timing relaxed as people many started working from home and public life came to a standstill. In an online survey with 435 respondents, we investigated the effects of the phase with the strictest COVID-19 restrictions on the relationship between social and biological rhythms as well as sleep during a six-week period (mid-March until end of April 2020) in three European societies (Austria, Germany, Switzerland).
Dr. LaMoreaux[/caption]
Brian LaMoreaux, M.D., M.S.
Medical Director, Medical Affairs
Horizon Therapeutics
MedicalResearch.com: What is the background for this study?
Response: Pegloticase is a PEGylated biologic therapy for patients with uncontrolled gout who have not improved on or could not tolerate conventional urate-lowering therapies. All biologics have the ability to engender anti-drug antibodies (ADAs) and it is known that some patients given pegloticase develop ADAs that cause them to stop treatment prior to receiving a complete course of therapy.
In other rheumatic autoimmune diseases, DMARDs such as methotrexate or azathioprine are used as standard of care to prevent the development of ADAs to biologics. These DMARDs often allow patients to remain on biologic therapies longer and receive the full therapeutic benefits while minimizing adverse events. While pegloticase has been used traditionally as monotherapy, recent case series have demonstrated the therapeutic benefit of immunomodulator co-administration, allowing more patients to receive a full course of pegloticase therapy. Little has been published on how widespread this practice is and whether it has changed over time.