Hilton Bay Bay, Boston, MA
2014-09-24
DAY ONE - SEPTEMBER 24-25, 2014
7:45 am Workshop Registration/Continental Breakfast
8:30 am WORKSHOP: Quantifying the Impact of Study Conduct on Study Results: Update and Review
(SEPARATE REGISTRATION REQUIRED) The epidemic of failure of clinical trials of analgesics and other therapeutic agents has given birth to an emerging science of clinical trials, the objective of which is to understand what factors related to study design and study conduct impact the observed effect sizes of treatments, and how those factors, which function as sources of measurement error, can be mitigated. This workshop will answer the following questions: ► What aspects of study conduct are known to impact outcome? ► How can these factors me monitored during study conduct? ► What corrective actions are available? ► What are the regulatory implications? The format of the session will be a sharing of experiences and practices after Dr. Katz presents initial comments. Participants will have the opportunity to bring their own experiences to the table. Participants will be asked to provide suggestions for “case types” that will stimulate discussion - examples of either failed study conduct, or examples of successful interventions to fix study conduct problems. Nathaniel Katz, MD, MS, President & CEO, Analgesic Solutions 10:00 am Conference Registration 10:40 am Chairperson's Opening Remarks William K. Schmidt, Ph.D., President, NorthStar Consulting, LLC, VP Clinical & Regulatory, Centrexion Corp., VP Clinical & Regulatory, Cap Genesis, LLC, VP Clinical Development, EicOsis, LLC 10:45 am Lighting the Song With Sense and Color: A Humanistic Approach to Pain Research The 2011 Institute of Medicine report “Relieving Pain in America” provides a framework for addressing arguably this nations number one health, social and economic problem. Academic colleges and universities have important roles to play in helping address the burden that chronic pain places on the individual and the community. The presentation will highlight some of the efforts that the University of New England is taking in the areas of pain research and pain education. Highlights include the growth of a coordinated basic science research program that is studying the neurobiology of pain, efforts to build a clinical patient-centered outcomes research group, and the implementation of a truly interdisciplinary and inter professional approach for better preparing healthcare professionals in the prevention and treatment of chronic pain. The engagement of the arts and humanities, as well as patients and their families, in the education and research efforts will also be highlighted. The goal of the presentation is to facilitate discussion with the audience on the topic and think about collaborative ways to accomplish goals of the IOM report. Ed Bilsky, Ph.D., Professor of Pharmacology, COM, Vice President of Research and Scholarship, University of New England 11:15 am Techniques for Minimizing the Impact of Subject Dropouts on the Validity of Analgesic Clinical Trials - Increased Retention through Subject Education Followed by a Primer on Imputation Techniques When it comes to subject dropouts, an ounce of prevention is worth a pound of cure. Subject and study staff education can reduce dropout rates. The lecture will focus on educational paradigms designed to reduce dropouts and their efficacy. Regardless of technique, dropouts cannot be eliminated. When dropouts occur, they need to be statistically accounted for utilizing accepted imputation methods. In the recently released FDA draft analgesic guidance, a significant amount discussion was devoted to the appropriate statistical handling of missing data. Dr. Singla will provide a primer on accepted imputation techniques for acute and chronic analgesic studies. Neil Singla, MD, Founder & Chief Scientific Officer, Lotus Clinical Research 11:45 am Mechanisms of Acute and Chronic Itch: Novel Targets to Treat an Unmet Need Chronic itch associated with dermatitis, kidney and liver disease, and other disorders affects upwards of 1/3 of Americans with estimated annual costs exceeding $100 Billion. Chronic itch can be as distressful as chronic pain, and in most cases antihistamines and other currently available treatments are ineffective. In this presentation, Dr. Carstens will focus on the recent identification of novel itch transduction molecules including protease-activated receptors, Mas-related G-protein-coupled receptors, and certain cytokine receptors that signal antihistamine-resistant types of itch. He will also discuss the recent identification of neuropeptides including gastrin releasing peptide, brain natriuretic peptide and substance P, that are involved in central itch neurotransmission, as well as the pathophysiological changes that occur under conditions of experimental chronic itch. Emphasis is placed on the identification of promising molecular targets for the development of novel antipruritic drugs and other treatment strategies to block itch at its source and at various points along the itch-signaling pathway. Earl Carstens, Ph.D., Distinguished Professor, Department of Neurobiology, Physiology and Behavior, University of California, Davis 12:15 pm Luncheon 1:25 pm A Nation in Pain Author, syndicated health columnist and former pain patient Judy Foreman will discuss the hidden epidemic of chronic pain, which affects 100 million Americans (more than cancer, diabetes, heart disease and AIDS combined). She will highlight the inadequate training doctors receive in medical school (fewer hours of pain education than veterinary students!), the woeful underfunding of federal pain research (1% of the massive NIH budget), gender inequalities in pain management and the pros and cons of traditional Western treatments (surgery, electrical stimulation,etc) as well as complementary treatments (acupuncture, massage, marijuana, exercise). She will discuss why the failure to treat pain better is tantamount to "torture by omission,"and what we can do to remedy this. Judy Foreman, Health Columnist, Author, A Nation in Pain: Our Biggest Health Problem 1:55 pm (tentative title) The Challenges of Diagnosing and Treating Schwannomatosis Pain Christine Sang, MD, MPH, Director, Translational Pain Research, Brigham and Women's Hospital 2:25 pm Targeting Neuroinflammation for Pain Relief Current analgesics predominately modulate pain transduction and transmission in neurons and have limited success in controlling disease progression. Accumulating evidence suggests that neuroinflammation, which is characterized by infiltration of immune cells, activation of glial cells and production of inflammatory mediators in the peripheral and central nervous system, has an important role in the induction and maintenance of chronic pain. He will discuss how astrocytes-produced chemokines (such as CXCL1) can enhance neuropathic pain via neuron-glial interactions. He will also highlight the anti-inflammatory and pro-resolution lipid mediators such as protectin and resolvins that act on immune cells, glial cells and neurons to resolve neuroinflammation, synaptic plasticity and pain. Targeting excessive neuroinflammation could offer new therapeutic opportunities for chronic pain and related neurological and psychiatric disorders. Ru-Rong Ji, Ph.D., Professor, Department of Anesthesiology and Neurobiology, Duke University Medical Center 2:55 pm Refreshment Break / Scientific Poster Session Viewing 3:25 pm Abuse-deterrent Opioids – Addressing Drug Abuse and Patient Needs Extended-release (ER) opioids are an important part of the multi-modal approach to the treatment of moderate-to-severe chronic pain. While conferring clinical advantages to patients, abusers seek to tamper with these formulations in order to rapidly release the opioid to elicit a euphoric effect. This can lead to a potentially fatal overdose. Currently available abuse-deterrent formulations (ADF) are an improvement over non-ADF ER analgesics, but are still readily manipulated. There are novel opioids in development that may provide both clinical and abuse liability advantages, which will be presented in this lecture. Objectives of this talk include the following: Understand the concept of abuse liability Differentiate the different types of ADFs Identify currently available products Understand the FDA guidance on ADF development Identify ADF analgesics in development Discuss clinical advantages of ADF opioids Discuss abuse liability of ADF v. non-ADF opioids Ernest A. Kopecky, Ph.D., MBA, VP Clinical Development | Head, Neuroscience TA, COLLEGIUM Pharmaceutical 3:55 pm Presentation TBA Daniel Legault, JD, Chief Executive Officer and Director, Antibe Therapeutics 4:25 pm PANEL SESSION: An Open Dialogue and Q&A with the Day's Presenters Moderator: William K. Schmidt, Ph.D., President, NorthStar Consulting, LLC, VP Clinical & Regulatory, Centrexion Corp., VP Clinical & Regulatory, Cap Genesis, LLC, VP Clinical Development, EicOsis, LLC 5:10 pm Wine and Cheese Reception DAY TWO - September 25, 2014 7:30 am Continental Breakfast 8:15 am An Effort to Overcome the Crisis of the Current Drug Discovery in Pain Therapeutics Modern approaches to target-based drug discovery have grossly failed to deliver safe and efficacious medicine for CNS afflictions such as pain. This led to a new (or could be a roll-back) approach for drug discovery emphasizing network pharmacology or systems biology. According to these new perspectives, the efficacious and safe therapeutics should be multi-targeting drugs; however, there has been no practical methodology to identify such a multi-targeting drug. Vivozon’s unique core technology is built upon a tissue-based phenotypic screening that enables rapid and continuous discovery of agents that attenuate pain signaling through the modulation of a variety of known and unknown targets encompassing polypharmacology or "transient drugs.” As a result of the effort, Vivozon has identified a morphine comparable analgesic candidate (VVZ-149) that has antagonistic activity on GlyT2 & 5HT2a. We will introduce the practical approach for multi-targeting drug and preclinical/clinical data of VVZ-149. Doo H. Lee, Ph.D., Chief Executive Officer, Vivozon, Inc. 8:45 am Diagnosing and Treating Spine/Joint Related Pain: Harnessing The Body’s Own Defense Mechanism In this presentation, Dr. Scuderi will discuss his research in developing biologic therapies for traumatic musculoskeletal diseases based on protease inhibitors, a generation 2 platform. He will discuss application of these biologic therapeutics to degenerative diseases of the joints and spine and will outline the science behind Cytonics’ FACT assay, which detects a unique biomarker in the inflammatory cascade that can assist physicians pinpoint the source of pain. Gaetano Scuderi, MD, Founder, President, Cytonics Corporation 9:15 Voltage Gated Sodium Channels, a Perennial Target for New Pain Therapies - Are We Making Any Progress? Advances in human genetics are continually increasing support for the role of voltage gated sodium channel function and dysfunction in modulation of pain signaling. This talk will provide an overview of recent advances in targeting voltage gated sodium channels for the development of new pain therapies and highlight some of the challenges that exist. Neil Castle, Ph.D., Director of Biology, Neusentis - Pfizer 9:45 am Refreshment Break / Scientific Poster Session Viewing 10:10 am Sex, Pain and Drugs A growing recognition that many aspects of human disease are highly sexually dimorphic has lead to a growing interest in defining the implications of this research for treatment of pain. Receptors for sex hormones are found in pain and analgesic mechanisms at all levels of the neuraxis, and sex differences in pain conditions and response to analgesics are well established in humans. Sex hormones have recently been shown to have rapid action at G-protein coupled receptors as well as their well-established effects on gene regulation. Sex hormones also have profound effects on pain and analgesia that differ dramatically between females and males. One of the most dramatic clinical example of sexual dimorphism in response to analgesics is for the kappa-opioid analgesics, which produces delayed onset anti-analgesia in men but not women. Jon Levine, MD, Ph.D., Professor of Medicine, University of California, San Francisco 10:40 am Peripherally Acting Mu Opioid Receptor Antagonists For the Treatment of Opioid Induced Constipation: A Changing Development and Regulatory Landscape Managing chronic pain often leads to patients dealing with the substantial burden of constipation associated with opioid therapy. Unlike other opioid side effects, tolerance to constipation generally does not develop over time. Despite available options, a large proportion of patients do not receive adequate relief and the unmet need remains high. Peripherally acting mu opioid receptor antagonists directly target the cause of opioid-induced constipation (OIC), but the path for developing safe and effective drugs in this class is challenging and continues to evolve. Clinical and regulatory perspectives, including the potential impact of a recent FDA Advisory Committee meeting, will be discussed within the context of drug development for peripherally acting mu opioid receptor antagonists in the treatment of OIC. Lee M. Techner, DPM, Principal and Chief Clinical Consultant, Stage Gate Partners 11:10 am P2X3 Antagonism for Sensitization-driven Signs and Symptoms of Common Diseases: POC Results in Distressing Respiratory, Somatosensory and Visceral Conditions Afferent Pharmaceuticals has progressed the first clinical stage P2X3 antagonist, AF-219, to completion of four “proof of concept” studies in patients with painful and/or irritative symptoms in respiratory, somatosensory (painful OA of the knee) and visceral (interstitial cystitis/bladder pain syndrome) disorders. Outcomes from these studies have confirmed a number of preclinical findings and suggest broad potential of this innovative primary afferent target. For example, an unprecedented efficacy response to AF-219 in a two week study in patients with chronic cough, who have very limited effective therapeutic options, was observed and indicates that relief from the distress of chronic cough – and the first new antitussive for 50 years - could be on the horizon. Clinical experience reveals an excellent safety profile following up to 4 weeks of dosing at “definitive” dose levels, and augurs well for long term development of P2X3 antagonists for a range of common sensory indications with very high unmet needs. Anthony P. Ford, Ph.D., Chief Scientific Officer. Afferent Pharmaceuticals 11:40 pm Preventative Effects of a Formulation of Nasal Oxytocin for Chronic and High Frequency Episodic Migraine Headache Patients Through Block of CGRP Release Chronic and high frequency migraine patients suffer with 15 or more or 9-14 headache days/month respectively, and are highly debilitated by these conditions. Treatment choices for these conditions are currently inadequate. Dr. Yeomans and his team have previously shown that trigeminal neurons possess oxytocin receptors the expression of which is highly dependent on inflammatory state. They have also shown that nasal application of oxytocin attenuates responses of brainstem neurons to painful stimulation and produces profound analgesia in craniofacial behavioral assays. In this presentation, he will show that these physiologic and behavioral effects are likely mediated by inhibition of release of calcitonin gene related peptide - a pain neurotransmitter associated both with neurogenic inflammation of the dura as well as central sensitization of trigeminal nuclear neurons. He will also will describe the results of a multi-center phase II chronic dosing study in chronic and high frequency episodic migraine patients, where we have observed that nasal application of our formulation of nasal oxytocin produces robust and sustained decreases in the frequency of migraine attacks as well as of secondary migraines symptoms including nausea and vomiting, photophobia, and phonophobia. Finally, he will speculate as to a CGRP-dependent mechanism underlying these results. David Yeomans, Ph.D., Director of Pain Research, Faculty of Anesthesia, Stanford University School of Medicine, Founder & Chief Scientist, Trigemina, Inc. 12:10 pm Luncheon 1:20 pm Methodological Challenges in Conducting Human Abuse Potential Studies Evaluating the abuse potential of new chemicals and new formulations has evolved over the past several years. Outcomes of a HAP study can be affected by the population studied, criteria for inclusion/exclusion, blinding techniques, adequacy of training, subject sensitivity to test and comparator drugs, and the experience level of staff conducting the study. An important objective for most HAP studies is to demonstrate less abuse potential than a competing drug or formulation with the expectation that the favorable comparative data would be included in the study drug label upon approval. However, limited data have been permitted in the product labels approved by FDA to date. This presentation will discuss important factors that could affect the success of a HAP study and the potential impact on labeling claims. Lynn R. Webster, MD, FACPM, FASAM, Vice President, Scientific Affairs, PRA Health Sciences, Past President, American Academy of Pain Medicine (AAPM) 1:50 Dissecting the Immune Response to Inflammatory Pain The molecular and cellular immune components involved in the pathogenesis of pain during inflammation are not yet well understood. Dr. Ghasemlou and colleagues have sought to characterize the cellular and molecular immune responses and their association with changes in pain behavior in two of the most commonly used models of inflammatory pain, that are widely used as preclinical surrogates of human disease. Their results highlight important distinctions between inflammatory models of pain, and the disparate contribution of immune cells to behavioral outcomes. Nader Ghasemlou, Ph.D., Research Fellow, Children's Hospital Boston & Harvard Medical School, F.M. Kirby Neurobiology Center 2:10 pm Panel Session: An Open Dialogue and Q&A with the Day's Presenters Moderator: William K. Schmidt, Ph.D., President, NorthStar Consulting, LLC, VP Clinical & Regulatory, Centrexion Corp., VP Clinical & Regulatory, Cap Genesis, LLC, VP Clinical Development, EicOsis, LLC 2:55 pm End of Conference
|