News Article | May 22, 2017
This marketing authorisation is based on results from a Phase III, randomised, double-blind, active-controlled, non-inferiority study (Study 311) which compared once-daily eslicarbazepine acetate as monotherapy to twice-daily, controlled-release carbamazepine in newly diagnosed adults with partial-onset seizures. The primary endpoint was the proportion of patients seizure-free for the entire 26-week evaluation period. The data show that 71.1% (n=276/388) of patients for eslicarbazepine acetate and 75.6% (n=300/397) of patients for controlled-release carbamazepine were seizure-free for six months or more, at the last evaluated dose (average risk difference -4.28%; 95% CI -10.3, 1.74%). The one-year seizure-freedom rate at the last evaluated dose was 64.7% (n=251/388) on eslicarbazepine acetate and 70.3% (n=279/397) on controlled-release carbamazepine (average risk difference: -5.46%; 95% CI: -11.88, 0.97%). "Epilepsy is a chronic disorder of the brain and one of the most common neurological conditions worldwide," said Eugen Trinka, Professor and Chair of Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University, Salzburg, Austria. "This approval brings the promise of a new monotherapy option for over half of patients with epilepsy who experience partial-onset seizures." Eslicarbazepine acetate has an innovative mode of action that is different from other sodium channel blockers., It selectively targets the slow inactivated state of the sodium ion channel (which has been implicated in the pathogenesis of epilepsy), preventing its return to the active state, and thereby reduces repetitive neuronal firing, based on animal data. The recommended starting dose is 400 mg once daily which should be increased to 800 mg once daily after one or two weeks. Based on individual response, the dose may be increased to 1,200 mg once daily. Some patients on a monotherapy regiment may benefit from a dose of 1,600 mg once daily. "We are pleased that adults with partial-onset epilepsy across Europe are now able to benefit from a once-daily monotherapy option that is simple to use, which may optimise their adherence," comments António Portela, CEO of Bial, Porto, Portugal. "Bial has an ongoing commitment to all people living with epilepsy and we look forward to continuing to work with the epilepsy community to bring this new indication to patients." "This decision for eslicarbazepine acetate by the European Commission reinforces Eisai's commitment to researching and developing neurological treatment options that have the potential to help people manage epilepsy more effectively. This milestone means that newly-diagnosed adult patients in Europe who experience partial-onset epilepsy will now have a broader range of treatment options available," comments Neil West, Vice President EMEA, Global Neurology Business Unit at Eisai. A safety analysis of the Phase III study showed that the tolerability profile of eslicarbazepine acetate was similar to that of twice-daily controlled-release carbamazepine. The side effects of eslicarbazepine acetate were mostly of mild intensity, and consistent with the known safety profile. Incidence rates of treatment-emergent adverse events (TEAEs) were similar but slightly higher in patients receiving controlled-release carbamazepine (77.7%) (n=320/412) versus eslicarbazepine acetate (75.3%) (n=302/401). Possibly-related TEAEs were also slightly higher at 49.5% (n=204/412) for controlled-release carbamazepine compared with 41.1% (n=165/401) for eslicarbazepine acetate, for serious possibly-related TEAEs (2.7% vs 2.0%) (n=11/412 vs n=8/401), and for TEAEs leading to withdrawal (18.0% vs 13.5%) (n=74/412 vs n=54/401). The most frequently reported possibly-related TEAEs for eslicarbazepine acetate were, in order of most frequent, dizziness, headache, somnolence, fatigue and nausea. The continued development of eslicarbazepine acetate underscores Bial's and Eisai's commitment to developing and delivering highly beneficial new treatments to help improve the lives of people with epilepsy. Eslicarbazepine acetate is a voltage-gated sodium channel blocker which selectively targets the slow inactivated state of the sodium ion channel. Further, eslicarbazepine acetate does not inhibit potassium efflux, which may reduce the potential for repetitive neuronal firings. The efficacy of eslicarbazepine acetate was demonstrated in an initial proof-of-concept phase II study and three subsequent phase III randomised, placebo controlled studies in 1,049 people with refractory partial onset seizures.,, Eslicarbazepine acetate is currently marketed in Europe and Russia by Bial and by Bial's licensee, Eisai Europe Limited, a European subsidiary of Eisai Co Ltd under the trade name Zebinix® or Exalief®. In the United States and Canada eslicarbazepine acetate (tradename Aptiom®) is marketed by Sunovion Pharmaceuticals Inc under an exclusive license from Bial. Epilepsy is one of the most common neurological conditions in the world, affecting approximately 6 million people in Europe, and an estimated 50 million people worldwide. Epilepsy is a chronic disorder of the brain that affects people of all ages. It is characterised by abnormal discharges of neuronal activity which causes seizures. Seizures can vary in severity, from brief lapses of attention or jerking of muscles, to severe and prolonged convulsions. Depending on the seizure type, seizures may be limited to one part of the body, or may involve the whole body. Seizures can also vary in frequency from less than one per year, to several per day. Epilepsy has many possible causes but often the cause is unknown. Founded in 1924, BIAL's mission is to discover, develop and provide therapeutic solutions within the area of health. In recent decades, BIAL has strategically focused on quality, innovation and internationalization. Bial is strongly committed to therapeutic innovation, investing more than 20 per cent of its turnover in Research and Development (R&D) every year. Bial has established an ambitious R&D program centered on the neurosciences and cardiovascular system. The company expects to introduce more new medicines to the market in the next years, strengthening its international presence based in its own innovative medicines and accomplishing the company's purpose of "Caring for your Health." For more information about Bial, please visit www.bial.com About Eisai Co Ltd Eisai Co Ltd. is a leading global research and development-based pharmaceutical company headquartered in Japan. We define our corporate mission as "giving first thought to patients and their families and to increasing the benefits health care provides," which we call our human health care (hhc) philosophy. With over 10,000 employees working across our global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to realise our hhc philosophy by delivering innovative products in multiple therapeutic areas with high unmet medical needs, including Oncology and Neurology. As a global pharmaceutical company, our mission extends to patients around the world through our investment and participation in partnership-based initiatives to improve access to medicines in developing and emerging countries. For more information about Eisai Co., Ltd., please visit www.eisai.com 1. Zebinix® (eslicarbazepine acetate) Summary of Product Characteristics. Available at: http://www.medicines.org.uk/emc/medicine/22376 Accessed May 2017. 2. Ben-Menachem E, et al. Efficacy of eslicarbazepine acetate versus controlled-release carbamazepine as monotherapy in patients with newly diagnosed partial-onset seizures; European Congress on Epileptology 2016: Abstract #0002 3. Hebeisen S, et al. Eslicarbazepine and the enhancement of slow inactivation of voltage-gated sodium channels: a comparison with carbamazepine, oxcarbazepine and lacosamide. Neuropharmacology 2015; 89:122-35 4. Kowacs P, et al. Safety and tolerability of eslicarbazepine acetate as monotherapy in patients with newly diagnosed partial-onset seizures. Presented at EAN 2016; abstract #P32045 5. Elger C, et al. Eslicarbazepine acetate: A double-blind, add-on, placebo-controlled exploratory trial in adult patients with partial-onset seizures. Epilepsia 2007; 48:497-504 6. Elger C, et al. Efficacy and safety of eslicarbazepine acetate as adjunctive treatment in adults with refractory partial-onset seizures: A randomised, double-blind, placebo-controlled, parallel-group phase III study. Epilepsia. 2009;50:454-63 7. Ben-Menachem E, et al. Eslicarbazepine acetate as adjunctive therapy in adult patients with partial epilepsy. Epilepsy Res. 2010;89(2-3):278-85 8. Gil-Nagel A, et al. Efficacy and safety of 800 and 1200 mg eslicarbazepine acetate as adjunctive treatment in adults with refractory partial-onset seizures. Acta Neurol Scand. 2009; 120:281-87 9. Epilepsy in the WHO European Region: Fostering Epilepsy Care in Europe. Available at: http://www.ibe-epilepsy.org/downloads/EURO%20Report%20160510.pdf Accessed May 2017
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2011.2.2.1-2 | Award Amount: 24.91M | Year: 2012
The goal of this proposal (INMiND) is to carry out collaborative research on molecular mechanisms that link neuroinflammation with neurodegeneration in order to identify novel biological targets for activated microglia, which may serve for both diagnostic and therapeutic purposes, and to translate this knowledge into the clinic. The general objectives of INMiND are: (i) to identify novel mechanisms of regulation and function of microglia under various conditions (inflammatory stimuli; neurodegenerative and -regenerative model systems); (ii) to identify and implement new targets for activated microglia, which may serve for diagnostic (imaging) and therapeutic purposes; (iii) to design new molecular probes (tracers) for these novel targets and to implement and validate them in in vivo model systems and patients; (iv) to image and quantify modulated microglia activity in patients undergoing immune therapy for cognitive impairment and relate findings to clinical outcome. Within INMiND we bring together a group of excellent scientists with a proven background in efficiently accomplishing common scientific goals (FP6 project DiMI, www.dimi.eu), who belong to highly complementary fields of research (from genome-oriented to imaging scientists and clinicians), and who are dedicated to formulate novel image-guided therapeutic strategies for neuroinflammation related neurodegenerative diseases. The strength of this proposal is that, across Europe, it will coordinate research and training activities related to neuroinflammation, neurodegeneration/-regeneration and imaging with special emphasis on translating basic mechanisms into clinical applications that will provide health benefits for our aging population. With its intellectual excellence and its crucial mass the INMiND consortium will play a major role in the European Research Area and will gain European leadership in the creation of new image-guided therapy paradigms in patients with neurodegenerative diseases.
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2011.2.4.3-1 | Award Amount: 8.25M | Year: 2012
Background: A significant proportion of pre-diabetics, show macro and micro vascular complications associated with hyperglycaemia. Although many trials have demonstrated the efficacy of lifestyle and pharmaceutical interventions in diabetes prevention, no trial has evaluated the extent to which mid- and long-term complications can be prevented by early interventions on hyperglycaemia. Aims: To assess the long-term effects on multiple complications of hyperglycaemia of early intensive management of hyperglycaemia with sitagliptin, metformin or their combination added to lifestyle intervention (LSI) (diet and physical activity), compared with LSI alone in adults with non-diabetic intermediate hyperglycaemia (IFG, IGT or both). Study Design: Long-term, multi-centre, randomised, partially double blinded, placebo controlled, phase-IIIb clinical trial with prospective blinded outcome evaluation. Participants will be randomised to four parallel arms: 1) LSI \ 2 placebo tablets/day; 2) LSI \ 2 Metformin tablets of 850 mg/day; 3) LSI \ 2 Sitagliptin tablets of 50 mg/day; 4) LSI \ 2 tablets of a fixed-dose combination of Sitagliptin 50mg and Metformin 850 /day. Active intervention will last for at least 3 years, and additional follow-up up to 5 years. Setting and population: Males and Females with pre-diabetes (IFG, IGT or both) aged 45 to 74 years selected from primary care screening programs in 15 clinical centres from 12 countries: Australia, Austria, Bulgaria, Germany, Greece, Italy, Lithuania, Poland, Serbia, Spain, Switzerland and Turkey. (N=3000) Main Outcomes: The primary endpoint is a combined continuous variable: the microvascular complication ndex (MCI) composed by a linear combination of the Early Treatment Diabetic Retinopathy Study Scale (ETDRS) score (based on retinograms), the level of urinary albumin to creatinine ratio, and a measure of distal small fibre neuropathy (sudomotor test by SUDOSCAN), measured during baseline visit and at 36th and 60th month visits after randomisation. In addition, this project will include the evaluation of early novel serological biomarkers of systemic inflammation, early micro-vascular damage, non-alcoholic fatty liver disease, insulin sensitivity and insulin secretion, and measures of quality of life, sleep quality (somnograms) and neuropsychological evaluation. Vascular function and structure will be evaluated in a subset of participants (n=1000), including cIMT and microvascular endothelial function measured by EndoPAT. Expected results: By evaluating the effect of aggressive treatments in pre-diabetes for the early prevention of diabetes complication, this project has the potential of changing the current paradigm of early management of hyperglycaemia. The ultimate goal is the development of a standardized core protocol for the early prevention of microvascular and other complications, impacting social cost as a result not only in health care, but also in disabilities at work.
Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2013-ITN | Award Amount: 4.19M | Year: 2014
Knee Osteoarthritis (KOA) is the most common chronic musculoskeletal disorder, currently affecting over 8 million people within the EU, for which currently no cure is available. Adverse biomechanics, affected through some of the major health issues of our time (ageing, obesity, sedentary lifestyle) lie at the heart of the disease. The research theme of the KNEEMO ITN is towards targeted and tailored interventions for KOA, and focuses on identifying the right patients for the right treatment at the right time. Research areas include anatomy, musculoskeletal modelling, prevention and early identification of patients, epidemiology, biomechanical mechanisms, and intervention studies. The KNEEMO training programme combines existing best practices from consortium members and is designed to equip researchers with skills and knowledge specific to the research field (KOA anatomy, pathology and disease mechanisms, musculoskeletal modelling, functional assessment, KOA interventions), generic research skills (epidemiology, methodology, statistics, clinimetrics, ethics), and complementary training (entrepreneurship, project management, product development, intellectual property issues). At the individual level, training will be provided through direct research project supervision and intersectoral exchange visits and secondments. At the network level, regular workshops, courses, and summer schools will be scheduled. Additionally, web-based seminars will be provided and a social media virtual learning environment will be available for continuous supervision, peer-support and expert help. Dissemination and outreach activities will also be undertaken to showcase project results and to communicate with both the scientific community and the general public to promote the importance of research and to raise public awareness of the Marie Curie Actions.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: SC1-PM-11-2016-2017 | Award Amount: 7.60M | Year: 2017
PACE aims to transform the treatment of patients suffering from critical limb ischemia (CLI), a disease with high medical need, because of limited treatment options and poor outcome by applying a novel, off-the-shelf allogeneic placenta-derived stromal cell product (PLX-PAD). Despite improvements in medical care and revascularization, patients with CLI continue to have a high risk of major amputation (below the knee or higher) and cardiovascular death (1-year amputation-free survival <60%; 10-year mortality 70%). CLI has a strong social impact and its incidence is rising worldwide, including in Europe. The prevalence of CLI in the population aged 6090 years is estimated as 1% (0.51.2%) with male to female ratio around 3:1. We will evaluate the efficacy, tolerability and safety of multiple intramuscular injections of HLA-unmatched allogeneic PLX-PAD for the treatment of CLI patients who are unsuitable for revascularization, in a randomized, double-blind, multicentre, placebo-controlled, parallel group phase II study. The European Medicine Agency (EMA) accepted PLX-PAD as pilot project for the new Adaptive Pathways to Patients to force timely access for patients to the new therapeutic option. The PACE consortium will go beyond the traditional clinical trial endpoints of safety and efficacy, by state-of-the-art characterizing molecular and functional signature of the PLX-PAD product(s), in depth investigating mechanisms-of-action of PLX-PAD therapy, and exploring biomarkers for understanding response/non-response in particular patients (stratification and therapy response markers). PACE partners are world-leading experts in scalable, clinical grade 3D-cell manufacturing approved by authorities, preclinical and clinical cell therapy, and biomarker analyses with well recognized expertise in designing and performing clinical trials, including those with Advanced Therapy Medicinal Products (ATMPs) integrated with in-patient biomarker and mechanistic side-studies.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-16-2015 | Award Amount: 5.97M | Year: 2016
Cardiovascular diseases including myocardial infarction (MI), which entails the irreversible loss of heart muscle tissue, constitute a major socio-economic burden in global healthcare. With whole organ transplantation as the only treatment option for end-stage heart failure, MI patients could particularly benefit from advanced cell therapies aimed at the functional reconstitution of damaged hearts. Human induced pluripotent stem cells (hiPSCs) can be derived by reprogramming patients somatic cells. In contrast to adult (stem) cells e.g. from blood, bone marrow or the heart, hiPSCs have unlimited expandability and differentiation potential into all relevant cell types including cardiomyocytes, endothelial cells, pericytes and connective tissue-forming cells, making them highly attractive as a universal cell source for organ repair. However, technologies for the robust therapeutic scale production of hiPSC-derived progenies in line with GMP standards and at reasonable cost are currently lacking. TECHNOBEATs ultimate objectives are 1) to advance therapeutic scale cell production through innovative bioreactor technologies and novel cell monitoring tools, and 2) to develop regulatory compliant bioprocessing of innovative iPSC-based cardiac -tissue. The clinical translation of cardiac -tissue will require 3) the development and application of tools for improved cell delivery and longitudinal in vivo monitoring of cell grafts, and 4) proof-of-concept for safety and functional integration in physiologically relevant preclinical models of cellular heart repair. Through its interdisciplinary excellence, TECHNOBEATs consortium of leading European stem cell researchers, clinicians, tissue-, bioprocess-, and technical- engineers in industry and academia is ideally positioned to address these ambitious objectives. It will provide new treatment options for suffering patients and increase Europes attractiveness as a hub for innovative medical technologies.
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.4.2-1 | Award Amount: 7.44M | Year: 2013
Children are often treated as small adultsnot as the special patients they are. Regulations exist to encourage the development of drugs and formulation for children. However, off-patent drugs are often administered to children without appropriate formulations or systematic investigations. Therefore, the paediatric use marketing authorisation (PUMA) has been designed. The EMA Paediatric Working Party has prioritized the unmet need for the cardiovascular off-patent drug enalapril in the European paediatric population. Enalapril is an ACE inhibitor commonly used for cardiac failure in children under 1 year of age, although it is not labelled for any condition in patients <20 kg in European countries. Current problems with the use of enalapril in children include: no appropriate formulation and insufficient stability of the liquid soluble formulation for young paediatric patients; insufficient paediatric pharmacokinetic (PK) data for any formulation; insufficient safety data in neonates, infants, and young children; and limited pharmacodynamics (PD) and efficacy data for paediatric cardiological indications. The aim of the LENA (Labeling of Enalapril from Neonates up to Adolescents) project is to address these shortcomings and provide a basis for a future PUMA of enalapril by developing an age-appropriate solid oral formulation suitable for all paediatric subsets; generating PK and PD data; collecting data on the safety of enalapril in young paediatric patients; and providing dose recommendations based on PK/PD modelling and bridging from adult data. The international collaboration of the LENA investigators will provide the required expertise to develop and evaluate drug formulation, investigate dosing, and recruit paediatric patients for clinical trials while respecting current legislation, regulatory considerations, and ethical aspects, with the aim of applying for a PUMA.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: SC1-PM-11-2016-2017 | Award Amount: 6.62M | Year: 2017
Stress Urinary Incontinence (SUI) is a disease affecting over 200 million people worldwide. It represents a condition with a prevalence of 20-50% in women, thereby creating an immense socio-economic burden. The currently available treatment strategies entail various complications and offer only short-term relief to the patients. Tissue engineering using autologous cells offers a feasible alternative for functional restoration of the damaged urinary sphincter muscle and represents an ideal treatment option that could reverse the underlying pathologic conditions. MUSIC aims at translating basic knowledge on regenerative medicine (RM) and stem cell therapy into the clinic by undertaking a first-in-man multisystem study using autologous muscle precursor cells (MPCs) in a combination with neuromuscular electromagnetic stimulation (NMES) in 40 female patients. We will carry out the specific tasks to prove safety and efficacy of the proposed novel multilevel treatment as well as reproducibility of the therapeutic effect. Additional objectives are optimization of the advanced-therapy medicinal product (ATMP) towards totally xeno-free and facilitated manufacturing as well as the introduction of a novel injection technique for more efficient and precise implantation of the final product. Combining expertise, MUSIC features a unique infrastructure, including the knowledge of experts in the fields of RM, urology, cellular biology and biomaterials throughout Europe (CH, NL, UK, A, D). The MUSIC consortium has an exclusive opportunity to determine the validity of this MPC cellular treatment in combination with NMES and to further improve its feasibility and clinical efficacy. The ultimate goal is to significantly improve the patients` quality of life and to exploit a future commercial opportunity by expanding the know-how to various smaller RM centers and companies within Europe, thus, making personalized medicine using autologous cells a more feasible SUI treatment option.
Trinka E.,Paracelsus Medical University
Epilepsia | Year: 2011
Current standard treatment of established status epilepticus after failure of benzodiazepines is intravenous phenytoin/fosphenytoin, phenobarbital, or valproate. Since 2006 two new antiseizure drugs have become available as intravenous formulation: levetiracetam (2006) and lacosamide (2008). Both drugs have been taken up very rapidly by the clinicians to treat acute seizures and status epilepticus, despite lack of evidence from randomized controlled trials. The favorable pharmacokinetic profile and the good tolerability, especially the lack of sedating effects of both drugs make them promising potential alternatives to the standard antiseizure drugs. Future randomized controlled trials are needed to inform clinicians better about the best choice of treatment in established status epilepticus. The experimental evidence as well as the current clinical experience with levetiracetam and lacosamide are summarized in this review. © Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.
Tauber M.,Paracelsus Medical University
Archives of Orthopaedic and Trauma Surgery | Year: 2013
Acromioclavicular joint (ACJ) injuries represent a common injury to the shoulder girdle. In the management algorithm of acute ACJ injuries complete radiological evaluation represents the key to a successful therapy. According to the classification of Rockwood the presence of a horizontal component in addition to vertical instability has to be detected. Using axillary functional views or Alexander views dynamic horizontal ACJ instability can be diagnosed in a simple, efficient and cost-effective manner reducing the number of mis-/underdiagnosed ACJ injuries. MRI should not be the imaging modality of first choice. The treatment of ACJ dislocations must consider two aspects. In addition to the correct type of injury therapy strategies should be adapted to patient's demands and compliance. Low grade AC injuries types I and II are treated non-operatively in terms of skilful-neglect. High-grade injuries types IV-VI should be treated operatively within a time frame of 2-3 weeks after injury. A certain debate is still ongoing regarding type III injuries. Out from the literature, non-operative treatment of type III injuries results to provide at least equal functional outcomes as compared to surgical treatment associated with less complications and earlier return to professional and sports activities. If surgical treatment is indicated, open surgical procedures using pins, PDS-slings or hook plates are still widely used concurring with recently raising minimally invasive, arthroscopic techniques using new implants designed to remain in situ. Combined coracoclavicular and acromioclavicular repair are gaining in importance to restore horizontal as well as vertical ACJ stability. © 2013 Springer-Verlag Berlin Heidelberg.