Author Interviews, Immunotherapy, Leukemia, Stem Cells, Transplantation / 12.08.2016

MedicalResearch.com Interview with: Felix Garzon, MD, PhD Senior Vice President Head of Clinical Development Actinium Pharmaceuticals, Inc. New York, NY 10016 MedicalResearch.com: What is the background for this study? What is goal of this Study? Response: Iomab-B (“Iomab”) was developed at the Fred Hutchinson Cancer Research Center (“the Hutch”) in Seattle, Washington. The Hutch is a pioneer in the field of bone marrow transplantation (BMT) having 3 Nobel Prizes and doctors there performed some of the first transplants for leukemia patients. Iomab-B is intended to be an induction and conditioning agent prior to a BMT for patients with relapsed or refractory Acute Myeloid Leukemia (AML) who are over the age of 55. BMT is the only potentially curative option for AML i.e. for this patient population that currently has a survival prognosis of 2-6 months which means that if Iomab-B is successful it would create a new market segment and offer patients a great clinical benefit and a hope for a cure. Actinium Pharmaceuticals licensed Iomab from the Hutch in 2012 and prior to us licensing Iomab, it had been studied in almost 300 patients in several phase 1 and phase 2 clinical trials in an array of blood cancers, both leukemias and lymphomas. Actinium is now the sponsor of a pivotal phase 3 trial for Iomab-B to study its use as an induction and conditioning agent prior to a bone marrow transplantation in patients with relapsed or refractory AML who are over the age of 55. This trial, which we have named the SIERRA (Study of Iomab-B in Elderly Relapsed or Refractory AML) trial, started at the end of June 2016 and we expect to enroll 150 patients by the end of 2017. The primary endpoint of the SIERRA trial is durable complete remissions (dCR) of 6 months. The study arm will consist of Iomab-B administration followed by a  bone marrow transplantation, patients will be evaluated for dCR at 6 months after engraftment, which will be assessed at day 28 or day 56. The control arm of the study will be physician’s choice of chemotherapy and if the patient is able to achieve a complete remission (CR) they may receive a BMT or some other form of treatment with curative intent. The study is designed to evaluate if the study arm of Iomab-B and a BMT can double the dCR rate of the control arm, which is designed to replicate the current treatment regimen prior to a bone marrow transplantation . (more…)
Author Interviews, Gastrointestinal Disease, Gluten, Immunotherapy / 27.07.2016

MedicalResearch.com Interview with: Armin Alaedini, PhD Assistant Professor Department of Medicine & Institute of Human Nutrition Columbia University Medical Center New York, NY 10032 MedicalResearch.com: What is the background for this study? Response: It has been a mystery why some people experience a range of symptoms in response to the ingestion of wheat and related cereals, even though they do not have celiac disease (an autoimmune disorder) or wheat allergy. Both gastrointestinal (GI) symptoms, most commonly abdominal pain, diarrhea, and bloating, as well as extra-intestinal symptoms, such as fatigue, anxiety, depressed mood, and cognitive difficulties are reported by patients. The identity of the component(s) of wheat responsible for triggering the symptoms remains uncertain and it is not clear if gluten or non-gluten molecules are involved. There is evidence to indicate that wheat sensitivity also affects a subset of patients with irritable bowel syndrome (IBS), a common disorder. Despite the interest from the medical community and the general public, the causes and mechanism of the associated symptoms have remained unknown and no biomarkers are available to aid in the diagnosis of patients. (more…)
Author Interviews, Immunotherapy, Pulmonary Disease / 20.07.2016

MedicalResearch.com Interview with: Ganesh Raghu, M.D. FACP, FCCP Professor of Medicine Division of Pulmonary and Critical Care Medicine and Director of Center for Interstitial Lung Diseases Director, Interstitial Lung Disease/Sarcoid/Pulmonary Fibrosis Program University of Washington Medical Center Seattle, Washington MedicalResearch.com: What is the background for this study? Response: This is a new post-hoc analysis of the Phase III INPULSIS trials, including a total of 1,061 patients with idiopathic pulmonary fibrosis (IPF), which has been published in the American Journal of Respiratory and Critical Care Medicine. As background, achieving an accurate diagnosis of IPF in clinical practice is very complex and challenging. Physicians use an imaging technique called high resolution computed tomography (HRCT) to help them identify the presence of scarring (fibrosis) and, specifically, the presence of usual interstitial pneumonia (UIP) pattern in the lungs. The radiological changes called "honeycombing" are the key feature of the UIP pattern visible on HRCT and the pattern of UIP is the hallmark of the fibrosis in patients with IPF. In the absence of definitive UIP pattern on HRCT images of the lungs, the diagnosis of  idiopathic pulmonary fibrosis requires the microscopic features of UIP in the surgical lung biopsy (SLB) based on current guidelines for diagnosis of IPF. However, it can be challenging to confirm that scarring in the absence of honeycombing on HRCT meets the strict guideline criteria for a definitive diagnosis of IPF. For a large group of patients who do not receive a confirmed diagnosis of IPF according to guidelines, including those not eligible for surgical lung biopsy, the clinical course of their condition and the effectiveness of  idiopathic pulmonary fibrosis treatment remains unknown. Therefore, investigations into the behavior of the disease across diagnostic subgroups are important. (more…)
Author Interviews, Immunotherapy, Prostate Cancer / 16.07.2016

MedicalResearch.com Interview with: Julie Graff, M.D. Oncologist specializing in prostate cancer Knight Cancer Institute Oregon Health & Science University MedicalResearch.com: What is the background for this study? What are the main findings? Response: Men with metastatic prostate cancer that is not responding to second-line androgen receptor blockade (such as enzalutamide) have a very limited life expectancy. We found that adding immunotherapy to enzalutamide in men whose prostate cancer is no longer responding to enzalutamide could exert a very strong anti-cancer effect. Previous experience with this type of immunotherapy in prostate cancer patients suggested this type immunotherapy does not work in patients with prostate cancer. What we have found will lead to more studies of this agent. (more…)
Author Interviews, BMJ, Immunotherapy, Johns Hopkins, Rheumatology / 27.06.2016

MedicalResearch.com Interview with: Laura C. Cappelli, M.D Johns Hopkins University School of Medicine MedicalResearch.com: What is the background for this study? What are the main findings? Response: We had been referred several patients with inflammatory arthritis or dry mouth and dry eyes after being treated with immune checkpoint inhibitors. When searching the literature for information on how to evaluate and treat these patients, we realized that there was minimal information available. We wanted to describe our experience and inform the medical community about these events so that recognition could increase. (more…)
Author Interviews, Cancer Research, Chemotherapy, Immunotherapy / 15.06.2016

MedicalResearch.com Interview with: Professor Frances Balkwill OBE, FMedSci Lead, Centre for Cancer and Inflammation Barts Cancer Institute Queen Mary University of London London MedicalResearch.com: What is the background for this study? Prof. Balkwill: We wanted to find out if chemotherapy altered patients immune system especially the immune cells that co-exist with cancer cells in tumors. We studied women with ovarian cancer who often receive chemotherapy after diagnosis but before surgery. This meant, at least in some of them, we could study a biopsy taken before treatment began and also a biopsy taken during the operation. (more…)
ASCO, Author Interviews, Cancer Research, Immunotherapy / 08.06.2016

MedicalResearch.com Interview with: Dr. Arjun Balar MD Assistant Professor, Department of Medicine Co-Leader Genitourinary Cancers Program NYU Langone Medical Center Laura and Isaac Perlmutter Cancer Center MedicalResearch.com: What is the background for this study? Dr. Balar: Standard treatment for advanced urothelial cancer includes cisplatin chemotherapy. But more than half of patients are not expected to tolerate it well and alternative treatment is inferior to cisplatin. The average survival for these patients is in the range of 9-10 months with carboplatin-based treatment, which is the most commonly used alternative to cisplatin. Atezolizumab is a PD-L1 blocking antibody that reactivates the body¹s immune system to fight bladder cancer and has been recently FDA approved in the management of advanced urothelial cancer in the second-line setting after failure of platinum-based chemotherapy. (more…)
ASCO, Author Interviews, Cancer Research, Immunotherapy, University of Pittsburgh / 07.06.2016

MedicalResearch.com Interview with: Robert L. Ferris, M.D., Ph.D. Robert L. Ferris, M.D., Ph.D. UPMC Endowed Professor and Vice-Chair Associate Director for Translational Research Co-Leader, Cancer Immunology Program MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Ferris: Investigators at the University of Pittsburgh Cancer Institute<http://upci.upmc.edu/> (UPCI) co-led CheckMate-141<https://clinicaltrials.gov/ct2/show/NCT02105636> a large, randomized international phase III clinical trial that enrolled 361 patients with recurrent or metastatic head and neck squamous cell carcinoma who had not responded to platinum-based chemotherapy, a rapidly progressing form of the disease with an especially poor prognosis. Patients were randomized to receive either nivolumab or a single type of standard chemotherapy until tumor progression was observed. Nivolumab, which belongs to a class of drugs known as immunotherapeutics, enables the body’s immune system to destroy cancer cells. It currently is approved to treat certain types of cancers, including melanoma and lung cancer. The nivolumab group achieved better outcomes than the standard chemotherapy group by all accounts. After 12 months, 36 percent of the nivolumab group was alive, compared to just 17 percent of the standard chemotherapy group. Nivolumab treatment also doubled the number of patients whose tumors shrunk, and the number whose disease had not progressed after six months of treatment. Importantly, these benefits were achieved with just one-third the rate of serious adverse events reported in the standard chemotherapy group. In addition, on average, patients receiving nivolumab reported that their quality of life remained stable or improved throughout the study, while those in the chemotherapy group reported a decline. The new trial was considered so successful that it was stopped early to allow patients in the comparison group to receive the new drug. (more…)
Author Interviews, Gastrointestinal Disease, Immunotherapy / 07.06.2016

MedicalResearch.com Interview with: William J. Sandborn, MD Professor of Medicine and Adjunct Professor of Surgery Chief, Division of Gastroenterology Director, UCSD IBD Center University of California San Diego and UC San Diego Health System MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Sandborn: The Phase 3 IM-UNITI study investigated the efficacy and safety of Stelara (ustekinumab) in the treatment of moderate to severe Crohn’s disease as an every 8 or 12 week maintenance therapy. The study showed a significant proportion of adults with moderate to severe Crohn’s disease who received Stelara maintenance treatment achieved clinical remission. (more…)
ASCO, Author Interviews, Biomarkers, Cancer Research, Cost of Health Care, Immunotherapy / 07.06.2016

MedicalResearch.com Interview with: Neil T. Mason, MBA Personalized Medicine Strategist Personalized Cancer Medicine Division of Population Science Moffitt Cancer Center MedicalResearch: What is the background for this study? What are the main findings? Response: Immune checkpoint inhibitors targeting PD-1 (nivolumab and pembrolizumab) and CTLA-4 (ipilimumab) have revolutionized the treatment of metastatic disease in melanoma and non-small cell lung cancer with additional indications showing positive results. These drugs have elicited profound and durable responses in a significant number of patients, but have been criticized for their high cost. Though the price of the drugs themselves can reach over $100,000 per year, they can also cause severe, life threatening toxicities that are difficult and expensive manage. This model utilizes patient data from a large, NCI-designated cancer center to estimate the average cost of treatment with immune checkpoint inhibitors based on average duration of treatment and reported incidence of major toxicities. Based on the model, PD-1 inhibitor therapies are less costly than ipilimumab due to the significantly higher cost per dose of ipilimumab and average treatment duration of less than a year for PD-1 inhibitors. Managing drug-related toxicities were estimated to contribute between $8,200 and $9,600 to the cost of therapy with nivolumab adding the most cost. (more…)
ASCO, Author Interviews, Brain Cancer - Brain Tumors, Cancer Research, Immunotherapy / 04.06.2016

MedicalResearch.com Interview with: Wayne L. Furman, MD Department of Oncology Jude Children's Research Hospital Memphis, TN 38105-3678 MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Furman: Despite improvement in 2-yr EFS from 46% to 66% with the inclusion of dinutuximab, a monoclonal antibody that recognizes a glycoprotein on neuroblasts called ‘GD2’ (disialoganglioside), more than one-third of children with high-risk neuroblastoma still are not cured. Therefore novel therapeutic approaches are needed for this subset of patients. The clinical evaluation of various anti-GD 2 monoclonal antibodies in children with neuroblastoma has been exclusively focused on treatment of patients after recovery from consolidation, in a state of ‘minimal residual disease’. This is because traditionally chemotherapy has been thought to be too immunosuppressive to combine with monoclonal antibodies. However recent studies suggest, even in the setting of “bulky” solid tumors, the combination of chemotherapy with monoclonal antibodies can enhance the effectiveness of the antibodies. First, chemotherapy can increase the efficacy of antibodies by depleting cells of the immune system that suppress immune function. Also chemotherapy-induced tumor cell death can trigger tumor antigen release, uptake by antigen processing cells and an enhanced antitumor immune response. There is also data that anti-GD2 monoclonal antibodies can suppress tumor cell growth independent of immune system involvement. Furthermore anti-GD2 monoclonal antibodies and chemotherapy have non-overlapping toxicities. All of these reasons were good reasons to evaluate the addition of a novel anti-GD2 monoclonal antibody, called hu14.18K322A, to chemotherapy, outside the setting of minimal residual disease, in children with newly diagnosed children with high-risk neuroblastoma. (more…)
Author Interviews, Dermatology, Immunotherapy / 01.06.2016

MedicalResearch.com Interview with: Benjamin M. Perry, DO Silver Falls Dermatology Salem, OR 97302 MedicalResearch.com: What is the background for this study? Dr. Perry: Our interest in this subject developed when a patient came into our clinic with concern of multiple new nevi developing on palmoplantar surfaces following initiation of treatment with Rituximab. We conducted a review of the existing literature and found that this wasn’t a known adverse effect. From that point, we wanted to know the pathogenesis, prognosis, and management for eruptive nevi that developed in the setting of medication use. A collective review had not been previously performed on this subject. In essence, we had questions that were unanswered and set out to find the answers. (more…)
Author Interviews, Cancer Research, Dermatology, Immunotherapy, Melanoma, NYU / 21.05.2016

MedicalResearch.com Interview with: Melissa A. Wilson, MD, PhD Assistant professor of Medical Oncology NYU Langone Perlmutter Cancer Center MedicalResearch.com: What are the most common types of skin cancer? Dr. Wilson: Basal cell carcinoma, squamous cell carcinoma and melanoma. With rare exception, all are related to sun exposure. MedicalResearch.com: Are some types of skin cancer more serious than others? Dr. Wilson: Melanoma is the most serious form of skin cancer, with the highest risk of developing into metastatic disease. Most basal cell and squamous cell carcinomas are superficial and not as invasive, so removal is the treatment. Rarely, these can cause invasive and metastatic disease, but this occurs infrequently. Melanoma is much more serious. Of course, the earlier melanoma is detected and the earlier stage that it is, is more predictive of a favorable outcome. MedicalResearch.com: Who is most prone to skin cancer? Dr. Wilson: Persons with excessive sun exposure, fair skin, light hair and blue eyes - although it can certainly occur in anyone. (more…)
Author Interviews, Cancer Research, Colon Cancer, Immunotherapy, Leukemia, Multiple Sclerosis, Neurology / 13.05.2016

MedicalResearch.com Interview with: PD Dr. Mathias Buttmann Senior Consultant Neurologist and Head of the Multiple Sclerosis Outpatient Clinic University of Wuerzburg Wuerzburg, Germany  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Buttmann: The synthetic anthracenedione mitoxantrone is approved for disease-modifying treatment of patients with aggressive forms of relapsing or secondary progressive multiple sclerosis (MS). It has been known for years that this DNA-intercalating agent increases the risk of acute myeloid leukemia. We performed a retrospective cohort study to investigate whether mitoxantrone also increases the risk for other types of malignancies. We included all 677 mitoxantrone-treated  multiple sclerosis patients who were seen at our large German academic MS centre between 1994 and 2007 and collected follow-up information on the occurrence of malignancies, death and causes of death as of 2011. Follow-up was complete in 676 patients. The median age at mitoxantrone initiation was 41 years and the median follow-up duration was 8.7 years. We identified 37 patients with a malignancy after mitoxantrone initiation, among them 4 cases of acute myeloic leukemia and 7 cases of colorectal cancer. Compared to the general population matched for sex, age and year of occurrence, we calculated an 1.5-fold increased incidence of any type of malignancy, a tenfold increased incidence of acute myeloic leukemia and a threefold increased incidence of colorectal cancer, while the incidence of other types of malignancies was not increased. Higher age at mitoxantrone initiation but neither higher cumulative mitoxantrone dose nor treatment with other immuosuppressive agents was identified as a malignancy risk factor. Fifty-five patients had died, among them 12 from a malignancy. Our study confirmed previous reports on an increased incidence of acute myeloic leukemia after mitoxantrone treatment and newly described an association between mitoxantrone therapy and an increased incidence of colorectal cancer. (more…)
Author Interviews, Immunotherapy, JAMA, Multiple Sclerosis, UCSF / 02.05.2016

MedicalResearch.com Interview with: Jennifer Graves, MD, PhD, MAS Adult and Pediatric Multiple Sclerosis Centers UCSF MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Graves: Cessation of medications with effects on immune trafficking may be more likely to cause rebound inflammatory activity in autoimmune diseases such as multiple sclerosis.  We observed 5 strikingly severe relapses consistent with rebound events following cessation of fingolimod treatment and identified several similar cases in the literature.  At our center the rebound events occurred with an approximate 10% frequency. MedicalResearch.com: What should clinicians and patients take away from your report? Dr. Graves: Fingolimod cessation may be complicated by rebound phenomena in some patients, similar to what has been observed with natalizumab. Both of these medications have effects on immune cell trafficking, likely explaining the association with rebound events.  Careful consideration must be taken in stopping these medications. (more…)
Author Interviews, Cancer Research, Immunotherapy, NEJM / 02.05.2016

MedicalResearch.com Interview with: Paul Nghiem, MD, PhD Professor & Head, University of Washington Dermatology George F. Odland Endowed Chair Affiliate Investigator, Fred Hutchinson Cancer Research Center Professor, Adjunct, of Pathology and Oral Health Sciences Clinical Director, Skin Oncology, Seattle Cancer Care Alliance UW Medical Center at Lake Union Seattle WA 98109   MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Nghiem: Merkel cell carcinoma (MCC) is about 30 times less common than malignant melanoma, but about 3 times more likely to kill a patient than a melanoma. There is no FDA-approved therapy for this cancer & chemotherapy typically only provides about 90 days prior to the cancer progressing. Because of the strong links between MCC and the immune system, including the fact that most MCCs are caused by a virus, there was interest in trying to use immune checkpoint therapy to treat advanced Merkel cell carcinoma. The response to immune stimulation with anti-PD1 therapy was about as frequent as to chemotherapy (56% of patients responded) but importantly, among the responders, 86% remained in ongoing responses at a median of 7.6 months.  While still early, this appears to be strikingly more durable than responses to chemotherapy. (more…)
Author Interviews, Immunotherapy / 19.03.2016

MedicalResearch.com Interview with: Dr. Emerson C. Perin MD, PhD Texas Heart Institute Medical Director, BSLMC Catheterization Laboratory Director, Research in Cardiovascular Medicine Medical Director, Stem Cell Center  MedicalResearch.com: What is the background for this study? Dr. Perin: Critical limb ischemia (CLI) is a devastating and debilitating disease characterized by reduced blood flow to the legs, frequently as a consequence of atherosclerosis. Patients with CLI have a poor prognosis and live with chronic pain and disability. The disease manifests clinically as pain during rest and compromised wound healing, often resulting in ulcers that don’t heal, which can lead to amputation. Moreover, Critical limb ischemia is a deadly disease, with an annual mortality rate of about 20%. The only effective treatment option is revascularization, but not all CLI patients are good candidates for this approach, and even for those who are, procedures can fail. These patients face a dismal prospect as no other effective treatment options are available. Clearly, new therapeutic strategies are desperately needed for this group of patients. One of the most exciting new approaches for Critical limb ischemia patients who have no options is the concept of therapeutic angiogenesis—improving regional blood flow by facilitating the growth of blood vessels. This can be accomplished by delivering angiogenic factors to the area in need of improved blood supply. Hepatocyte growth factor (HGF) is a promising novel biologic for use in this way because it’s a powerful angiogenic agent that stimulates cell proliferation and migration. Delivering HGF into the ischemic limbs of patients with CLI may result in beneficial effects that help restore compromised blood flow to the area and encourage better healing of wounds. VM202 is a plasmid DNA that simultaneously expresses two isoforms of HGF, mimicking the way the body produces HGF. On the basis of favorable results from phase 1 clinical trials showing that gene therapy with VM202 was safe, well-tolerated, and potentially beneficial in patients with ischemic diseases, we conducted a phase 2, dose-escalation clinical trial in patients with Critical limb ischemia. (more…)
Allergies, Author Interviews, Immunotherapy / 14.03.2016

MedicalResearch.com Interview with: Stacy L. Rosenberg, MD UPMC Montefiore Allergy and Immunology Fellow MedicalResearch.com: What is the background for this study? Dr. Rosenberg: Allergy shots or allergen immunotherapy (AIT) is an effective therapy for allergic rhinoconjunctivitis (hay fever).  Low adherence has been a significant barrier, whereas rush immunotherapy to environmental allergens provides rapid build-up and offers quicker efficacy, which may improve adherence.  However, there have been concerns for increased risk of systemic reactions with rush protocols.  We describe a new protocol for modified rush AIT that offers quicker build-up towards a maintenance dose with improved safety and lower risk of systemic reactions.  We also hypothesize that there are specific characteristics that distinguish patients who develop systemic reactions in the setting of modified environmental rush immunotherapy (MERIT). MedicalResearch.com: What are the main findings? Dr. Rosenberg: Overall, MERIT has a good safety profile.  A subset of patients did develop systemic reactions, which were mild.  Lower BMI was associated with systemic reactions and there was a trend between history of urticaria (hives) and younger age with development of systemic reactions.  Significantly more patients with systemic reactions had allergen extracts containing cat, dust mite, and weed pollen.  Neither gender, asthma, nor anaphylaxis history were associated with an increased risk of systemic reactions. (more…)
Author Interviews, Dermatology, Immunotherapy / 08.03.2016

MedicalResearch.com Interview with: Dr. Andrew Blauvelt MD MPH President of Oregon Medical Research Center  MedicalResearch.com: What is the background for this study? Dr. Blauvelt: Secukinumab (brand name Cosentyx)is a monoclonal antibody directed against interleukin 17A, a key cytokine involved in psoriasis pathogenesis. Efficacy and safety of secukinumab treatment for moderate-to severe psoriasis has been previously published. There are relatively few head-to-head comparison studies between biologic therapies for psoriasis, making direct comparison of these drugs difficult. (more…)
Author Interviews, Immunotherapy / 29.01.2016

MedicalResearch.com Interview with: Dr. Mark Heffernan PhD Dr. Mark Heffernan is a Nexvet co-founder, and has served as Chief Executive Officer and a member of the Nexvet board of directors since April 2011. In 2003, Dr. Heffernan co-founded Opsona Therapeutics Ltd., an Irish biotechnology company focused on human mAbs for inflammatory and oncology diseases. He also worked in R&D and business development roles for two Australia biotechnology companies, Antisense Therapeutics Limited and Metabolic Pharmaceuticals Pty Ltd., for a number of years. Dr. Heffernan has a BSc in Biochemistry and Pharmacology and a Ph.D. in Biochemistry from Monash University (Australia). MedicalResearch.com: Tell me about Nexvet and its background? What is the company’s mission statement or goal? Dr. Heffernan:   Nexvet is a public (NASDAQ: NVET) clinical-stage biopharmaceutical company focused on developing and commercializing novel, species-specific biologics for companion animals (pets). We were founded five years ago and our mission has been to transform animal medicine by leading the introduction of biologic therapies (monoclonal antibodies and therapeutic proteins) into everyday veterinary practice. Many chronic conditions stand to benefit from biologic options, just as they have in human medicine, such as inflammation and cancer. Taking products with validation in human medicine is part of Nexvet’s development strategy, which leverages human data from these innovative therapies and rapidly advances the veterinary equivalents. MedicalResearch.com: Can you tell us about the PETization™ platform? What is it designed to do? Dr. Heffernan:   PETization™ is Nexvet’s proprietary approach to monoclonal antibody (mAb) candidate design. It uses an algorithmic approach, ‘crunching’ libraries of natural antibody sequence data to rapidly design mAbs that are “100% species-specific” to a target species. This significantly reduces the risk of an immunogenic reaction, while preserving the parent (or ‘starting’) mAb’s affinity for its target. PETization has demonstrated a reduction in the time and cost typically associated with the development of monoclonal antibodies using conventional methods, such as CDR grafting and its affinity maturation. Thus far Nexvet has used PETization to successfully convert human and rodent mAbs into canine, feline and equine mAbs. These candidates have demonstrated safety and efficacy across the clinical development spectrum including proof-of-concept (every species) right through to late-stage pivotal studies (in dogs). (more…)
Author Interviews, Immunotherapy, NEJM, Transplantation, UCSF / 29.01.2016

MedicalResearch.com Interview with: Dr. Flavio Vincenti, M.D Clinical Professor of Medicine and Surgery Departments of Medicine and Surgery Endowed Chair in Kidney Transplantation University of California, San Francisco San Francisco, CA 94143 Medical Research: What is the background for this study? What are the main findings? Dr. Vincenti: This is a phase 3 study of belacept immunosuppression as compared to cyclosporine based immunosuppression in renal transplant recipients randomly assigned to 2 treatments arms of belatacept and a controlled arm consisting of cyclosporine. The main finding of this study is that Belatacept, a fusion receptor protein that blocks co-stimulation and is administered intravenously on the maintenance of a 4 weekly maintenance therapy, had superior outcomes at 5 and 7 years as compared to patients on a CsA-based regimen. The 7 year data show that patients on either arm of belatacept had a 43 percent risk reduction of deaths or grafts loss as compared to patients treated with cyclosporine. In addition, belatcept patients had significantly better preservation of renal function throughout the 7 years of follow up and had lower incidence of donor specific antibodies. Nephrotoxicity from cyclosporine and donor specific antibodies are important causes of late graft loss. (more…)
Author Interviews, Breast Cancer, Immunotherapy, PLoS / 02.01.2016

MedicalResearch.com Interview with: David Gallego Ortega, PhD Group Leader, Tumour Development Group Cancer Division Garvan Institute of Medical Research Conjoint Lecturer, St Vincent’s Clinical School, Faculty of Medicine, UNSW, Australia National Breast Cancer Foundation and Cure Cancer Foundation Australia Fellow  Medical Research: What is the background for this study? What are the main findings? Dr. Ortega: We have identified a protein that 'goes rogue’ in breast cancer. The protein, called Elf5, ‘tricks' the immune system producing inflammation so that the immune cells now help the breast cancer cells to spread throughout the body. Cancer spread, or metastasis, is the ultimate cause of death of breast cancer patients, so we are very excited about our discovery because it opens the door to explore anti-inflammatory drugs that can be combined with existing therapies. We have found that luminal breast cancer patients that present high levels of Elf5 progress earlier in their disease. The Luminal subtype is the most common type of breast cancer, so these therapies will potentially benefit to 2/3 of all breast cancer patients. (more…)
Author Interviews, Immunotherapy, NEJM, Rheumatology / 24.12.2015

MedicalResearch.com Interview with: Prof. dr. D.L.P. Baeten MD Clinical Immunology and Rheumatology Academic Medical Center University of Amsterdam Amsterdam, The Netherlands Medical Research: What is the background for this study? What are the main findings? Prof. Baeten: Ankylosing spondylitis is a debilitating rheumatic condition which affects young adults and with NSAIDS and TNF inhibitors as only therapeutic option. Over the last years, we generated evidence that IL-17 is an important inflammatory mediator in this condition. In the two studies reported here in the NEJM, we demonstrate that IL-17 inhibition with secukinumab has a very profound and long-lasting effect on signs and symptoms as well as inflammation in ankylosing spondylitis patients, even in those patients that failed a TNF blocker before. (more…)
Author Interviews, Genetic Research, Immunotherapy / 22.12.2015

MedicalResearch.com Interview with: Benjamin Greenbaum, PhD Assistant Professor and Professor Nina Bhardwaj MD PhD Hematology and Medical Oncology Tisch Cancer Institute Icahn School of Medicine at Mount Sinai New York, NY 10029 Medical Research: What is the background for this study? Response: It has recently become clear that, due to epigenetic alterations, tumors transcribe non-coding RNAs that are typically silenced. Often such RNA emanates from the “dark matter” genome. Many of these regions consist of repetitive elements and endogenous retroelements that are rarely transcribed in normal tissue. At the same time, due to immunotherapy, understanding the role of the immune system and immune activation in tumors has become critically important. The activation of specific elements of the innate immune system in a tumor may have either beneficial or detrimental effects for patients. Moreover, recent work has suggested that endogenous element activation can lead to improved immunotherapy outcomes. Therefore, it is critically important to understand the nature of innate immune activation in tumors and what triggers are responsible for these responses. We have been developing methods to detect abnormal patterns in viral RNA that may indicate activation of the innate immune system. We have found that patterns of motif usage avoided in the evolution of viruses, such as influenza, indicate RNA features that provoke an innate immune response. The innate immune system is capable of sensing motifs in viruses. We tested directly whether these avoided patterns are immunostimulatory. (more…)
Author Interviews, Immunotherapy, Lymphoma, NYU / 11.12.2015

MedicalResearch.com Interview with: Dr. Catherine S. M. Diefenbach MD Assistant Professor of Medicine NYU Langone Laura and Isaac Perlmutter Cancer Center New York, NY 10016  Medical Research: What is the background for this study? What are the main findings? Dr. Diefenbach: The background of the study is that through an understanding of the unique immunobiology of Hodgkin lymphoma we can derive rational treatment strategies which may heighten the efficacy of existing therapies, and improve the outcomes for patients with relapsed disease.  In E4412 which is a national study sponsored by the Eastern Cooperative Oncology Group (ECOG-ACRIN) we explore the safety and efficacy of combination of the antibody drug conjugate brentuximab vedotin which targets CD30 on the surface of the Hodgkin lymphoma tumor cells, and immune stimulation of the T cells in the tumor microenvironment using checkpoint inhibitors.  We reported the data from the first arm of the study Brentuximab Vedotin and Ipilimumab.  To date 23 patients with relapsed Hodgkin lymphoma have been treated; the combination of brentuximab and ipilimumab was safe and well tolerated with primarily grade 1 and 2 toxicities.  In 18 patients evaluable for response the ORR was 72% with a complete response rate of 50%. (more…)
Author Interviews, Breast Cancer, Chemotherapy, Immunotherapy / 09.12.2015

MedicalResearch.com Interview with: Professor Michael Gnant, M.D., FASC Director and Chairman Department of Surgery President, Austrian Breast&Colorectal Cancer Study Group Head, Breast Health Center Vienna Comprehensive Cancer Center Vienna Medical University of Vienna - Department of Surgery Austria Medical Research: What is the background for this study? What are the main findings? Response: The background of this presentation is as follows: For many years, we have seen intriguing - but also sometimes conflicting - results of trials using adjuvant bone-targeted therapy. ABCSG-18 is a placebo-controlled trial of adjuvant denosumab 60mg twice yearly, and I have been able to present to you at this year’s ASCO meeting the dramatic reduction in clinical fractures which was the primary end point of the trial. We have also showed that twice yearly denosumab can be administered without added toxicity in this double-blind placebo-controlled trial. These results were as well published in the Lancet earlier this year. The obvious question remaining now is whether adjuvant treatment with the anti-RANK ligand antibody also improves outcomes in a way similar to what bisphosphonates do. Main findings of ABCSG-18: disease-free survival results of the intention-to-treat analysis: In the placebo group, we observed 203 DFS events. In the denosumab group, there were 167 DFS events, resulting in a hazard ratio of 0.816, indicating an 18% relative DFS improvement by denosumab. In terms of absolute differences, the benefit was 1.2% at 3 years, 2.1% at 5 years, and 3.1% at 7 years. (more…)
Annals Internal Medicine, Author Interviews, Dermatology, Gastrointestinal Disease, Immunotherapy / 09.12.2015

MedicalResearch.com Interview with: Isabelle Cleynen  PhD University of Leuven  Medical Research: What is the background for this study? What are the main findings? Dr. Cleynen : Ulcerative colitis and Crohn’s disease, together inflammatory bowel disease (IBD), are characterized by chronic inflammation of the gastrointestinal tract. Treatment for IBD usually involves drug therapy including anti-inflammatory drugs and immune system repressors, amongst which biologics as the anti-TNF antibodies used for patients with moderate to severe IBD. Although these TNF-blocking drugs are effective in many patients with immune-mediated disorders like psoriasis, rheumatoid arthritis and spondylarthropathies, and IBD, several case reports and series showed that some patients developed troubling skin problems (including psoriasis and eczema), causing them to stop the anti-TNF treatment. It is however not clear how often these skin problems develop in IBD patients treated with anti-TNF, and what could be the predisposing factors. In a retrospective cohort of 917 IBD patients initiated on anti-TNF therapy in a single center, we have studied which patients did and did not develop skin problems, what type of skin problems, how they were treated, and whether the lesions resolved upon treatment. We found that about one third of the patients developed skin problems while being treated with anti-TNF drugs. The most common type was psoriasiform eczema, often occurring in flexural regions, the scalp, and genitalia. The time between starting the TNF-blocking drug and the appearance of the skin problem varied from less than half a year to more than 4 years. Quite surprisingly, we found that the cumulative dose of the treatment, or drug serum levels were not different in skin and non-skin lesion patients. Skin lesion patients however seemed to be younger when diagnosed with IBD and when started on anti-TNF agents, more often had anti-nuclear and dsDNA antibodies (both auto-immune factors), and a higher number of skin-disease related genetic risk variants. Most patients had a good response to treatment of their skin problem. About 10% of the patients who developed skin problems, however, stopped the TNF-blocking treatment because of this issue. (more…)
Author Interviews, Cancer Research, Chemotherapy, Hematology, Immunotherapy / 09.12.2015

MedicalResearch.com Interview with: Dr. Ajai Chari MD Associate Professor Medicine, Hematology and Medical Oncology Tisch Cancer Institute Mount Sinai School of Medicine New York, NY Medical Research: What is the background for this study? Dr. Chari: This is a heavily pretreated population where the median progression free survival (PFS) of the pomalidomide dexamethasone is only 4 months and ORR is only 31%. While the anti CD38 monoclonal antibody daratumumab has single agent has activity in this setting, patients with rapidly progressive disease need combination therapy to achieve rapid and deep responses. Pomalidomide also upregulates CD38 on MM cells and like daratumumab, increases the effector cell activity against myeloma. Thus, there is a strong preclinical and clinical rationale for combining daratumumab with pomalidomide and dexamethasone. (more…)
Author Interviews, HIV, Immunotherapy, PLoS / 04.12.2015

MedicalResearch.com Interview with: Andreas Meyerhans, PhD ICREA Research Professor at the University Pompeu Fabra Infection Biology Group Department of Experimental and Health Sciences Universitat Pompeu Fabra Barcelona Spain Medical Research: What is the background for this study? What are the main findings? Dr. Meyerhans: In brief, chronic HIV infections lead to a dampening of HIV-specific killer cells. This phenomenon is named exhaustion and is mediated by inhibitory proteins, such as PD-1, on the cell surface. A consequence of exhaustion is a reduction of the immune control over virus expansion. We have studied the effect of blocking the negative signaling from the inhibitory proteins by means of PD-1/PD-L1 pathway inhibition on effector and regulatory T cells (Treg). We found that one can augment antiviral immune control only when the virus load was well controlled in the HIV-infected individuals i.e. by antiviral drugs. In that case, PD-1/PD-L1 pathway blockage led to an expansion of anti-HIV killer cells over Treg cells. This latter are suppressive white blood cells also subject to the same inhibitory pathway regulation. In contrast, when blood cells from viremic HIV-infected individuals were analyzed, Treg cells expanded efficiently and thus reduced the effector to regulatory T cell ratio that controls HIV. Taken together, our data point to Treg cells as an important component in the outcome of PD-1/PD-L1 pathway inhibitor therapies and suggest a net gain in anti-HIV immune responses only when the HIV loads are well controlled during the administration of these novel compounds. (more…)