WPC Banner  
 
Archived Content

Targeting Pain with Novel Therapeutics

 

Day 1 | Day 2 
Download World Pharma Congress Final Brochure or Download Targeting Pain Conference Brochure 

Despite an increased understanding of the biology and neurophysiology of pain, and a wealth of novel targets to pursue, new pain therapeutics struggle to prove efficacy and meet primary endpoints in the clinic. Now in its fifth year, Targeting Pain with Novel Therapeutics offers an established forum for pain researchers from across pharma and academia to gather to hear the latest developments in pre-clinical candidates and models, advances in translational strategies, and updates on clinical results.

» Recommended Short Courses 

Animal Models of Pain 


12:30 pm Registration

1:20 Chairperson’s Opening Remarks

Jeffrey Kennedy, Ph.D., Senior Research Fellow, Neuroscience Discovery Research, Eli Lilly & Co.


» 1:25 KEYNOTE PRESENTATION
From Mechanisms to Medicines: What ACTTION Can be Taken to Accelerate Analgesic Drug Development?

Robert DworkinRobert H. Dworkin, Ph.D., Professor of Anesthesiology, Neurology, Oncology, and Psychiatry; Professor, Center for Human Experimental Therapeutics, University of Rochester School of Medicine and Dentistry; Director, Analgesic Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION), a public-private partnership with the FDA

A substantial percentage of patients with pain either are refractory to existing analgesic treatments or obtain only partial relief of their pain. To address the limitations of existing analgesics, the FDA has established a public-private partnership. The primary objective of this partnership is to accelerate the identification of treatments with improved efficacy and safety. One important focus of the partnership’s activities involves optimizing clinical trial methods to increase assay sensitivity and study efficiency.

 

EARLY ASSESSMENT OF CLINICAL EFFICACY 

2:10 A Novel Genetic Based Approach for Demonstrating Target Engagement of Nav1.7 Inhibitors

Y. Paul Goldberg, M.B., Ch.B., Ph.D., FRCPC, Vice-President, Clinical Development, Xenon Pharmaceuticals, Inc.

Demonstrating proof-of-mechanism (POM) in a fast and economical manner is crucial for the timely and successful development of new Nav1.7 inhibitors. We have used a rare genetic condition, inherited erythromelalgia (IEM), to develop a novel model for rapid assessment of target engagement for these inhibitors. IEM is an autosomal dominant disorder of spontaneous or easily evoked pain in the hands and feet, caused by SCN9A missense mutations resulting in gain-of-function in Nav1.7. Therefore, therapeutics that inhibit Nav1.7 are expected to relieve the pain associated with IEM. Pain in IEM patients can be readily evoked under experimental conditions by providing a heat stimulus. Here we describe the features of this model in a context of an exploratory clinical trial conducted with a novel, potent Nav1.7 small molecule inhibitor (XEN402). A randomized, double-blind, two-period crossover study was conducted in four mutation-proven IEM patients. XEN402 or matching placebo was given orally in each treatment period (2 days), separated by a 2-day washout. Patient reported outcomes of pain intensity and/or relief were recorded and the time taken to induce pain was measured. XEN402 significantly suppressed the IEM pain induction compared to placebo (42% less pain, p = 0•014), demonstrating POM in this patient population. Important insights were gained from this study in the optimization of this model. The results of this study showed that the IEM pain can be reliably induced, standardization of experimental conditions and pain induction methods are important, heat can be used as a safe and reliable method of pain induction, the time required for pain induction can be used as a useful endpoint, and repeated pain and induction measurements are required for data interpretation. This pilot study showed that XEN402 blocks Nav1.7 mediated pain associated with IEM, thereby demonstrating the utility of using rare genetic disorders with mutant target channels as a novel approach to evaluate sodium channel inhibitors to demonstrate rapid target engagement.

2:40 Pharmacology and First Clinical Experience of the Dual Enkephalinase Inhibitor PL37

Bernard P. Roques, Ph.D., Vice President & Scientific Director, Pharmaleads
Michel Wurm, M.D., Director, Drug and Business Development, Pharmaleads

Chronic pain remains unsatisfactorily treated and few novel painkillers have reached the market in the past century. An innovative approach is to increase the endogenous opioid peptides, enkephalins levels, by inhibiting their two inactivating ectopeptidases. Oral PL37 induces peripheral analgesia in various models of inflammatory and neuropathic pain (NP) without morphine side effects. Phase I/II clinical studies of PL37 showed remarkable safety and tolerability. PL37 was significantly more active than placebo in voluntary humans on capsaicin model of NP.

3:10 Clinical Development of the Peripheral Kappa Opioid Agonist CR845 

James B. Jones, M.D., Pharm.D., FACEP, CMO, Cara Therapeutics, Inc.

3:40 Refreshment Break in the Exhibit Hall with Poster Viewing

4:10 Are Alternative Pre-Clinical Pain Models andor Endpoints Really Needed?

Anthony W. Bannon, Ph.D., Associate Director II, Neuroscience Drug Discovery, Global Pharmaceutical Research & Development, Abbott

There are significant pressures in pharmaceutical research and development to improve success of bringing novel therapeutics to market.  In the area of pain research, one area that receives a significant amount of attention for needing improvement is the pre-clinical models, particularly rodent models.  The primary criticism is that the pre-clinical models do not adequately predict clinical efficacy.  More specifically, the criticism focuses on examples of agents that have shown efficacy in pre-clinical models but failed to show efficacy in human pain trials. This line of criticism bolsters the interest in identifying alternative models and endpoints to the standards currently used in pain research.  Examples include examination of endpoints in the pre-clinical models that measure on-going pain versus evoked pain.  This may be important given the role of on-going pain in many human pain conditions.  However, there are examples of the standard pre-clinical models predicting human efficacy and the back translation of known human analgesic agents in the pre-clinical models has in general been successful.  This presentation will further explore the use of these pre-clinical models for predicting efficacy of novel pain therapeutic agents.

4:40 Interactive Discussion Groups

Concurrent problem-solving discussions on specific topics, to provide a forum for exchanging ideas, voicing opinions and meeting potential collaborators. Discussions will be led by a moderator/s, limited to 15 participants per table, and open to all attendees and exhibitors.

Clinical Assessment of Pain

Robert H. Dworkin, Ph.D., Professor of Anesthesiology, Neurology, Oncology, and Psychiatry; Professor, Center for Human Experimental Therapeutics, University of Rochester School of Medicine and Dentistry; Director, Analgesic Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION), a public-private partnership with the FDA

Animal Models of Pain

Steve McGaraughty, Ph.D., Head, Electrophysiology, Abbott Labs

The Next Generation of Opioid Theapeutics

Edward Bilsky, Ph.D., Professor, Pharmacology & Director, Center of Excellence in the Neurosciences, University of New England

5:40 End of Day



Day 1 | Day 2 
Download World Pharma Congress Final Brochure or Download Targeting Pain Conference Brochure