News Article | May 5, 2017
Combatting Opioid Addiction: Janssen, Cara Therapeutics, Nektar, Pharmaleads and Centrexion Meet to Discuss Developments in Safe Pain Management Industry Set to Gather for 17th Annual Pain Therapeutics Summit to Combat Opioid Addiction and Access New Innovations in Safe Pain Management London, United Kingdom, May 05, 2017 --( Drawing insight from clinical results, industry case studies and scientific updates, agenda highlights will include: 1. Opening address from Janssen discussing conflicts surrounding pain research, economic value, using compounds and opioid addiction 2. Cara Therapeutics present clinical trial data on a novel peripherally acting kappa opioid receptor agonist that is currently in Phase 3 trials for post-operative pain (IV) and in Phase 2 trials for chronic pain (oral) 3. Nektar provide a clinical analysis looking at human abuse liability of a novel opioid agonist with inherently slow CNS entry 4. Pharmaleads present results of the first Dual ENKephalinase Inhibitors (DENKIs) to reach the clinic 5. An update on clinical candidates for migraine pain which have demonstrated clinical efficacy in a keynote by MSD USA on CGRP receptor antagonists 6. Centrexion Therapeutics case study on non-opioid analgesics in Morton’s Neuroma and Knee Osteoarthritis 7. Results from a CHDR study using a multimodal pain test battery 8. A spotlight on animal models featuring talks on translational pain research from Neurodigm, MD Biosciences, Zoetis and Grunenthal GmbH 9. Patient stratification based on somatosensory phenotyping - Mundipharma discuss implications for mechanism-based pain treatment and drug development 10. University of Manchester provide academic insight into brain mechanisms of vulnerability and resilience to pain 11. Lilly UK discuss how to improve the translatability of neurophysiological pharmacodynamic biomarkers in pain pathways 12. Insight into exploiting synergy in the neurotrophin pathway to provide analgesia presented by AstraZeneca 13. Novartis provide guidance on using patient reported outcome measures (proms) in patient management and pain clinical trials 14. Direction on using potassium channels as pain and migraine targets by Amgen 15. Ipsen Innovation explore the biology of botulinum neurotoxin for treatment of chronic pain 16. Grunenthal Sweden provide a progressive outlook on patient drug development A detailed conference agenda and full speaker line-up is available at http://www.pain-therapeutics.co.uk A series of interviews with key speakers are also available to read in the event download centre at: http://www.smi-online.co.uk/goto/2017pain-therapeutics.asp#tab_downloads Pain Therapeutics 2017 22nd & 23rd May Copthorne Tara Hotel, London, UK Contact Information: For media enquiries contact Teri Arri on Tel: +44 (0)20 7827 6162 / Email: email@example.com About SMi Group: Established since 1993, the SMi Group is a global event-production company that specializes in Business-to-Business Conferences, Workshops, Masterclasses and online Communities. We create and deliver events in the Defence, Security, Energy, Utilities, Finance and Pharmaceutical industries. We pride ourselves on having access to the world’s most forward thinking opinion leaders and visionaries, allowing us to bring our communities together to Learn, Engage, Share and Network. More information can be found at http://www.smi-online.co.uk London, United Kingdom, May 05, 2017 --( PR.com )-- Just under 3 weeks remain until the industry gathers to assess the latest developments and innovations in effective and safe pain management at SMi’s 17th annual conference on Pain Therapeutics.Drawing insight from clinical results, industry case studies and scientific updates, agenda highlights will include:1. Opening address from Janssen discussing conflicts surrounding pain research, economic value, using compounds and opioid addiction2. Cara Therapeutics present clinical trial data on a novel peripherally acting kappa opioid receptor agonist that is currently in Phase 3 trials for post-operative pain (IV) and in Phase 2 trials for chronic pain (oral)3. Nektar provide a clinical analysis looking at human abuse liability of a novel opioid agonist with inherently slow CNS entry4. Pharmaleads present results of the first Dual ENKephalinase Inhibitors (DENKIs) to reach the clinic5. An update on clinical candidates for migraine pain which have demonstrated clinical efficacy in a keynote by MSD USA on CGRP receptor antagonists6. Centrexion Therapeutics case study on non-opioid analgesics in Morton’s Neuroma and Knee Osteoarthritis7. Results from a CHDR study using a multimodal pain test battery8. A spotlight on animal models featuring talks on translational pain research from Neurodigm, MD Biosciences, Zoetis and Grunenthal GmbH9. Patient stratification based on somatosensory phenotyping - Mundipharma discuss implications for mechanism-based pain treatment and drug development10. University of Manchester provide academic insight into brain mechanisms of vulnerability and resilience to pain11. Lilly UK discuss how to improve the translatability of neurophysiological pharmacodynamic biomarkers in pain pathways12. Insight into exploiting synergy in the neurotrophin pathway to provide analgesia presented by AstraZeneca13. Novartis provide guidance on using patient reported outcome measures (proms) in patient management and pain clinical trials14. Direction on using potassium channels as pain and migraine targets by Amgen15. Ipsen Innovation explore the biology of botulinum neurotoxin for treatment of chronic pain16. Grunenthal Sweden provide a progressive outlook on patient drug developmentA detailed conference agenda and full speaker line-up is available at http://www.pain-therapeutics.co.ukA series of interviews with key speakers are also available to read in the event download centre at: http://www.smi-online.co.uk/goto/2017pain-therapeutics.asp#tab_downloadsPain Therapeutics 201722nd & 23rd MayCopthorne Tara Hotel, London, UKContact Information:For media enquiries contact Teri Arri on Tel: +44 (0)20 7827 6162 / Email: firstname.lastname@example.orgAbout SMi Group:Established since 1993, the SMi Group is a global event-production company that specializes in Business-to-Business Conferences, Workshops, Masterclasses and online Communities. We create and deliver events in the Defence, Security, Energy, Utilities, Finance and Pharmaceutical industries. We pride ourselves on having access to the world’s most forward thinking opinion leaders and visionaries, allowing us to bring our communities together to Learn, Engage, Share and Network. More information can be found at http://www.smi-online.co.uk Click here to view the list of recent Press Releases from SMi Group
Blak B.T.,Cegedim Strategic Data Medical Research Ltd. |
Smith H.T.,Lilly UK |
Hards M.,Cegedim Strategic Data Medical Research Ltd. |
Curtis B.H.,Lilly United States |
Ivanyi T.,Lilly Hungary
Diabetic Medicine | Year: 2012
Aims To describe patients with Type 2 diabetes mellitus treated with basal insulin, with or without oral antidiabetics in UK primary care, and evaluate insulin treatment patterns and factors explaining changes in therapy. Methods Retrospective analysis of patients with Type 2 diabetes within The Health Improvement Network UK primary care database. Patients receiving basal insulin between January and June 2006 were followed until July 2009. Results Analysis included 3185 patients, mean age 65.6years [standard deviation (SD) 12.4], 50.9% men, median diabetes duration 9.6years, median basal insulin use 1.3years, 86.5% had received oral antidiabetics in the previous 12months. Mean follow-up was 2.9years (SD 1.0), 59.8% patients maintained basal insulin throughout follow-up with a mean HbA1C of 69mmol/mol (SD 19; 8.4%, SD 1.7) at baseline and 65mmol/mol (SD 17; 8.1%, SD 1.6) during follow-up. During follow-up, 6.9% of patients discontinued, 19.3% intensified with and 14.1% switched to prandial or premixed insulin. Patients who intensified (prandial) had a mean HbA1c of 77mmol/mol (SD 18; 9.2%, SD 1.6) before change and a mean HbA1c of 71mmol/mol (SD 21; 8.6%, SD 2.0) at the end of the study. Those switching to premixed insulin had a mean HbA1c of 80mmol/mol (SD 18; 9.5%, SD 1.7) before change and a mean HbA1c of 69mmol/mol (SD 17; 8.5%, SD 1.5) at the end of the study. Increasing HbA1c and longer diabetes duration explained intensification and switch. Conclusions The majority of patients had HbA1c above the 53mmol/mol (<7%) target at baseline and post-intensification/switch. The HbA1c levels were reduced by intensification/switch suggesting that insulin changes did have some impact. Most patients did not change insulin treatment despite having higher than recommended HbA1c levels. Reasons for not changing treatment in face of unsatisfactory clinical outcomes are unclear. Further research is warranted to explore barriers towards therapy change. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.
Cellek S.,Cranfield University |
Cameron N.E.,University of Aberdeen |
Cotter M.A.,University of Aberdeen |
Fry C.H.,University of Bristol |
Ilo D.,Lilly UK
Nature Reviews Urology | Year: 2014
Benign prostatic hyperplasia (BPH)-related lower urinary tract symptoms (LUTS) and erectile dysfunction commonly coexist, and both respond to phosphodiesterase (PDE) 5 inhibitors, suggesting a shared pathophysiological mechanism. We propose that both BPH-LUTS and erectile dysfunction are caused by microvascular dysfunction within the pelvic organs, and we present an overview of preclinical and clinical studies supporting the hypothesis that, within both the penis and the lower urinary tract, a combination of endothelial and neural dysfunction leads to a vicious cycle of hypoxia, vasoconstriction, altered smooth muscle contractility, and degeneration of autonomic neurons and ganglia. This hypothesis explains much of the preclinical and clinical research relating to these two conditions, and provides a rationale for further investigation into the effects of PDE5 inhibitors on the pathophysiology and symptoms of BPH-LUTS. © 2014 Macmillan Publishers Limited. All rights reserved.
Chapple C.R.,Sheffield Hallam University |
Roehrborn C.G.,Southwestern Medical Center at Dallas |
McVary K.,University of Illinois at Springfield |
Ilo D.,Lilly UK |
And 2 more authors.
European Urology | Year: 2015
Background The international prostate symptom score (IPSS) evaluates lower urinary tract symptoms (LUTS) in men with suspected benign prostatic hyperplasia (BPH); the total score does not differentiate between storage and voiding and is unevenly weighted (four questions [57%] on voiding, three questions [43%] on storage). Objective To evaluate the relative contributions of storage and voiding IPSS subscores to total IPSS at baseline and in response to treatment with tadalafil. Design, setting, and participants Integrated analysis of data from four placebo-controlled, 12-wk studies of tadalafil (5 mg once daily) in 1499 men with LUTS/BPH. Outcome measurements and statistical analysis Relationships between total IPSS and the storage and voiding subscores were assessed using graphical exploration and linear regression modelling. Linear modelling was performed for the baseline and endpoint and for changes in subscores. The optimal storage subscore to total IPSS (S:T) ratio for IPSS improvement was identified using nonparametric regression and gradient-descent optimisation. Results and limitations The contribution of storage and voiding subscores at baseline and endpoint was 38.8% and 61.2%, and 39.2% and 60.7%, respectively. This intuitive 40:60 storage-to-voiding ratio was similar at baseline and endpoint by treatment group and for changes in subscores, but spanned the entire range for individuals. Changes in total IPSS were greatest for a storage subscore percentage contribution to total IPSS of 42.7%. There was no statistical association between S:T ratio (≥40% vs <40%) at baseline and response to tadalafil. The main limitation was the use of unvalidated storage and voiding IPSS subscores. Conclusions A constant S:T ratio of 4:10 was observed at baseline and endpoint. The greatest effect on total IPSS was noted for an S:T percentage contribution of 42.7%. Tadalafil efficacy was unaffected by the level of storage dysfunction at baseline. Patient summary This analysis shows that for men with BPH, improvements during treatment with tadalafil apply to both storage and voiding symptoms at a constant ratio. The extent of storage dysfunction before treatment did not affect the response to treatment. © 2014 European Association of Urology.
Mancini M.,Eli Lilly and Company |
Wade A.G.,CPS Research |
Perugi G.,University of Pisa |
Lenox-Smith A.,Lilly UK |
Schacht A.,Lilly Deutschland GmbH
Journal of Psychiatric Research | Year: 2014
An increasing rate of antidepressant trials fail due to large placebo responses. This analysis aimed to identify variables influencing signal detection in clinical trials of major depressive disorder. Patient-level data of randomized patients with a duloxetine dose ≥60mg/day were obtained from Lilly. Total scores of the Hamilton Depression Rating scale (HAM-D) were used as efficacy endpoints. In total, 4661 patients from 14 studies were included in the analysis. The overall effect size (ES), based on the HAM-D total score at endpoint, between duloxetine and placebo was-0.272. Although no statistically significant interactions were found, the following results for factors influencing ES were seen: a very low ES (-0.157) in patients in the lowest baseline HAM-D category and in patients recruited in the last category of the recruitment period (-0.122). A higher ES in patients recruited in centers with a site-size at but not more than 2.5 times the average site-size for the study (-0.345). Study characteristics that resulted in low signal detection in our database were: <80% study completers, a HAM-D placebo response >5 points, a high variability of placebo response (SD>7 points HAM-D), >6 post baseline visits per study, and use of an active control drug. Simpler trial designs, more homogeneous and mid-sized study sites, a primary analysis based on a higher cutoff blinded to investigators to avoid the influence of score inflation in mild patients and, if possible, studies without an active control group could lead to a better signal detection of antidepressive efficacy. © 2014 The Authors.
Blak B.T.,Cegedim Strategic Data Medical Research Ltd. |
Smith H.T.,Lilly UK |
Hards M.,Cegedim Strategic Data Medical Research Ltd. |
Maguire A.,United Biosource Corporation |
Diabetic Medicine | Year: 2012
Diabet. Med. 29, e191-e198 (2012) Aims This study characterized UK primary care patients with Type 2 diabetes who initiated insulin treatment, and described the initial insulin regimens used, overall metabolic changes and health-care resource usage. Methods A retrospective cohort study was performed using quality-checked patient data from The Health Improvement Network database. Eligible patients who initiated insulin for the first time between 2004 and 2006 were grouped into four cohorts according to the type of insulin regimen initiated. Data on patient characteristics, metabolic and clinical outcomes and health-care resource use were collected at baseline and during 6months of follow-up. Results In total, 4045 eligible adults [2269 male, 1776 female; mean age 62.6±13.3years; mean baseline HbA 1c 82±22mmol/mol (9.6%±2.0%)] initiated insulin. Approximately half (52.4%) initiated insulin as basal insulin only, 41.6% as premixed only, 4.0% as basal-bolus and 2.1% as prandial insulin only. Among patients with ≥180days follow-up (n=3815), the initial insulin regimen was not changed during follow-up in 75.1% of patients, while 13.7% discontinued, 7.0% switched and 4.7% intensified insulin therapy. The mean change in HbA 1c was -14mmol/mol (-1.3%, n=2881), with 17.3% of patients achieving an HbA 1c of <53mmol/mol (7%, n=3024). The mean weight change was +0.9kg (n=2345). Conclusions Basal and premixed insulin were the most common types of insulin initiated and in most patients no changes were made to the initial regimen over 6months. However, few patients achieved glycemic control targets. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.
Beaudet A.,IMS Health |
Palmer J.L.,IMS Health |
Timlin L.,Lilly UK |
Wilson B.,Lilly UK |
And 3 more authors.
Journal of Medical Economics | Year: 2011
Objective: To compare the cost-utility of exenatide once weekly (EQW) and insulin glargine in patients with type 2 diabetes in the United Kingdom (UK). Research design and methods: The IMS CORE Diabetes Model was used to project clinical and economic outcomes for patients with type 2 diabetes treated with EQW or insulin glargine. Treatment effects and patient baseline characteristics (mean age: 58 years, mean glycohaemoglobin: 8.3%) were taken from the DURATION-3 study. Unit costs and health state utility values were derived from published sources. As the price of EQW is not yet known, the prices of two currently available glucagon-like peptide-1 products were used as benchmarks. To reflect diabetes progression, patients started on EQW switched to insulin glargine after 5 years. The analysis was conducted from the perspective of the UK National Health Service over a time horizon of 50 years with costs and outcomes discounted at 3.5%. Sensitivity analyses explored the impact of changes in input data and assumptions and investigated the cost utility of EQW in specific body mass index (BMI) subgroups. Main outcome measures: Incremental cost-effectiveness ratio (ICER) for EQW compared with insulin glargine. Results: At a price equivalent to liraglutide 1.2?mg, EQW was more effective and more costly than insulin glargine, with a base case ICER of £10,597 per quality-adjusted life-year (QALY) gained. EQW was associated with an increased time to development of any diabetes-related complication of 0.21 years, compared with insulin glargine. Three BMI subgroups investigated (<30, 30-35 and >35 kg/m2) reported ICERs for EQW compared with insulin glargine ranging from £9425 to £12,956 per QALY gained. Conclusions: At the prices investigated, the cost per QALY gained for EQW when compared with insulin glargine in type 2 diabetes in the UK setting, was within the range normally considered cost effective by NICE. Cost effectiveness in practice will depend on the final price of EQW and the extent to which benefits observed in short-term randomised trials are replicated in long-term use. © 2011 Informa UK Ltd.
Mortensen M.,University College London |
Ebert B.,Lundbeck |
Wafford K.,Lilly UK |
Smart T.G.,University College London
Journal of Physiology | Year: 2010
The activation characteristics of synaptic and extrasynaptic GABAA receptors are important for shaping the profile of phasic and tonic inhibition in the central nervous system, which will critically impact on the activity of neuronal networks. Here, we study in isolation the activity of three agonists, GABA, muscimol and 4,5,6,7-tetrahydoisoxazolo[5,4-c]pyridin-3(2H)-one (THIP), to further understand the activation profiles of α1β3γ2, α4β3γ2 and α4β3δ receptors that typify synaptic- and extrasynaptic-type receptors expressed in the hippocampus and thalamus. The agonists display an order of potency that is invariant between the three receptors, which is reliant mostly on the agonist dissociation constant. At δ subunit-containing extrasynaptic-type GABAA receptors, both THIP and muscimol additionally exhibited, to different degrees, superagonist behaviour. By comparing whole-cell and single channel currents induced by the agonists, we provide a molecular explanation for their different activation profiles. For THIP at high concentrations, the unusual superagonist behaviour on α4β3δ receptors is a consequence of its ability to increase the duration of longer channel openings and their frequency, resulting in longer burst durations. By contrast, for muscimol, moderate superagonist behaviour was caused by reduced desensitisation of the extrasynaptic-type receptors. The ability to specifically increase the efficacy of receptor activation, by selected exogenous agonists over that obtained with the natural transmitter, may prove to be of therapeutic benefit under circumstances when synaptic inhibition is compromised or dysfunctional. © 2010 The Authors. Journal compilation © 2010 The Physiological Society.
Jones R.C.F.,Loughborough University |
Chatterley A.,Loughborough University |
Marty R.,Loughborough University |
Owton W.M.,Lilly UK |
Elsegood M.R.J.,Loughborough University
Chemical Communications | Year: 2015
3-Aryltetrahydrobenzisoxazoles prepared en route to the coleophomone natural products and analogues, were found to undergo a remarkable base-mediated rearrangement to 2-aryltetrahydrobenzoxazoles. The scope of this unprecedented, facile transformation was probed: a range of analogues was produced, a mechanism proposed, and an application demonstrated by synthesis of a known herbicidal compound. © The Royal Society of Chemistry 2015.
Ferrari F.D.,University of Glasgow |
Pasqua A.E.,University of Glasgow |
Ledgard A.J.,Lilly UK |
Marquez R.,University of Glasgow
Organic and Biomolecular Chemistry | Year: 2013
The enantioselective synthesis of the oxa-pinnaic acid framework has been achieved through internal asymmetric induction. The synthetic strategy pursued illustrates the adaptability of the Achmatowicz oxidative rearrangement for the synthesis of complex spirocyclic pyrans starting from tertiary alcohols. This journal is © The Royal Society of Chemistry.