Global Alliance for TB Drug Development

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Global Alliance for TB Drug Development

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News Article | May 20, 2017
Site: www.prlog.org

Experts Call on Ministers of Health to Support African Union-Endorsed Candidate at World Health Assembly -- In an open letter to Ministers of Health today, 35 of the world's top global health leaders expressed support for Dr. Tedros Adhanom Ghebreyesus of Ethiopia to become the next Director-General of the World Health Organization (WHO). On Tuesday (23 May), WHO Member States will select the next Director-General at the World Health Assembly in Geneva – a decision that will greatly impact health and lives of people around the world.Dr. Tedros' high-level endorsers – representing a broad cross section of the most influential people in global health in 23 countries and 5 continents – have called him the "most capable, qualified candidate".  They note his proven record reforming Ethiopia's health system, bringing primary healthcare to the country, cutting child mortality by 2/3, reducing HIV infections by 90% and malaria and tuberculosis deaths by 75% and 64%.These leaders – with long experience working in international health – also highlighted Dr. Tedros's public health and diplomatic leadership as well as his integrity, humility, and decisiveness."Dr. Tedros not only has the vision and experience to lead the world toward achieving the ambitious aims of the Sustainable Development Goals, including universal health coverage, but also the hands-on experience to be a supportive, credible partner to countries in efforts to achieve them," the leaders stated.The full text of the letter can be found on the campaign website and the list of signatories below.A wide-range of other leaders including former Heads of State, health, foreign affairs, development ministers, prominent academics and civil society advocates have also endorsed Dr. Tedros, found on the campaign website at www.drtedros.com Dr. Tedros served as Minister of Health (2005-2012) and Minister of Foreign Affairs (2012-2016) of Ethiopia, leading comprehensive reform which created more than 3,500 health centers; 16,000 health posts; trained 38,000 health extension workers; increased medical school enrollment; helped to improve supply chain and health information systems, and access to medicines. Dr. Tedros' public health experience is matched by experience in diplomacy and political leadership. As Board Chair of 2 major global health institutions – the Global Fund to Fight AIDS, Tuberculosis and Malaria and the Roll Back Malaria Partnership. He also played a key role in negotiating the landmark Addis Ababa Action Agenda, where countries committed to co-finance the Sustainable Development Goals.If elected, Dr. Tedros would be the 1st WHO Director-General from Africa – as well as the 1st former Minister of Health or former Minister of Foreign Affairs to serve in this role., Distinguished Visiting Professor, University of Johannesburg;Former Executive Director, African Academy of Sciences, Former President, International Federation of Gynecology and Obstetrics (FIGO); Former President, Royal College of Obstetricians and Gynaecologists, U.K., Senior Researcher and former Vice-President of Health Production and Innovation, Fiocruz, Brazil; former Executive Director, UNITAID, Geneva; former Unit Chief of Essential Medicines, Vaccines and Health Technologies at PAHO/WHO, Washington, Chief Executive Officer, Speak Up AfricaGlobal health and anti-poverty advocate, Executive Deputy Director, Institute for Global Health, Peking University, Director, Partners in Health Rwanda; Former Board Chair, International AIDS Vaccine Initiative, Professor of Clinical Public Health, Global Health and Surgery, University of Toronto, WHO Regional Director Emeritus (Europe), Founder and President, Speak Up Africa, Vice Provost for Global Initiatives and Chair, Department of Medical Ethics and Health Policy, University of Pennsylvania, President, University of Miami; Former Minister of Health, Mexico, Founder & Chief Executive, Rozaria Memorial Trust; African Union Ambassador on Ending Child Marriage, Midwife; Retired WHO Staff Member; Founder, Edna Adan Hospital & University; Former Foreign Minister and Former First Lady, Somaliland Republic, Former WHO Country Representative to Ethiopia; Former Senior Adviser to WHO Director-General Dr. Lee Jong-wook, Co-Founder and Former President, Global Health Advocates; Managing Director, Æquitas Consulting Pvt. Ltd., 7th President, African Development Bank (2005-2015), Chair, Global Health Innovative Technology Fund, Japan, Regional Director, Partners In Population and Development, Africa Regional Office, Director, Africa Centres for Disease Control and Prevention, Women & Girls Advocate, Youth Leader, Partnership Manager at SEED Project, Former Assistant Administrator for Global Health, U.S. Agency for International Development, Member of Parliament, Lok Sabha, Odisha, India, CEO, Big Win Philanthropy;Former Minister of Health, Nigeria; Adjunct Professor, Duke University Global Health Institute, U.S.Executive Director, International Civil Society Support; Former Executive Director Dutch AIDS Fonds and STOP AIDS NOW, Founding CEO, Global Alliance for TB Drug Development;Founding CEO, Foundation for Innovative and New Diagnostics;Chairman, Next2People Foundation, Former President, International Planned Parenthood Federation; Former Chairman, National Population Council of Ghana, Founder-President, Wellbeing Foundation Africa, Clinical Professor, Obstetrics and Gynaecology and Medical Genetics, University of British Columbia, Canada, Founder and Former President, Women Deliver; Founder and Former President, Family Care International, Chief Executive Officer, Grand Challenges Canada, Director, Centre of Excellence in Women and Child Health, Aga Khan University, East Africa, Director of Healthcare Research, William Davidson Institute, University of Michigan, Former Director, China Program, Bill & Melinda Gates Foundation; Former Director, China Office, U.S. Centers for Disease Control and Prevention; Former Chief of Health and Nutrition, UNICEF


Ma Z.,Global Alliance for TB Drug Development | Lienhardt C.,WHO | McIlleron H.,University of Cape Town | Nunn A.J.,Medical Research Council Clinical Trials Unit | Wang X.,Tianjin Centres for Disease Control and Prevention
The Lancet | Year: 2010

Drugs for tuberculosis are inadequate to address the many inherent and emerging challenges of treatment. In the past decade, ten compounds have progressed into the clinical development pipeline, including six new compounds specifically developed for tuberculosis. Despite this progress, the global drug pipeline for tuberculosis is still insufficient to address the unmet needs of treatment. Additional and sustainable efforts, and funding are needed to further improve the pipeline. The key challenges in the development of new treatments are the needs for novel drug combinations, new trial designs, studies in paediatric populations, increased clinical trial capacity, clear regulatory guidelines, and biomarkers for prediction of long-term outcome. Despite substantial progress in efforts to control tuberculosis, the global burden of this disease remains high. To eliminate tuberculosis as a public health concern by 2050, all responsible parties need to work together to strengthen the global antituberculosis drug pipeline and support the development of new antituberculosis drug regimens. © 2010 Elsevier Ltd. All rights reserved.


Dodd P.J.,University of Sheffield | Gardiner E.,Global Alliance for TB Drug Development | Coghlan R.,TESS Development Advisors | Seddon J.A.,Imperial College London
The Lancet Global Health | Year: 2014

Background: Confirmation of a diagnosis of tuberculosis in children (aged <15 years) is challenging; under-reporting can result even when children do present to health services. Direct incidence estimates are unavailable, and WHO estimates build on paediatric notifications, with adjustment for incomplete surveillance by the same factor as adult notifications. We aimed to estimate the incidence of infection and disease in children, the prevalence of infection, and household exposure in the 22 countries with a high burden of the disease. Methods: Within a mechanistic mathematical model, we combined estimates of adult tuberculosis prevalence in 2010, with aspects of the natural history of paediatric tuberculosis. In a household model, we estimated household exposure and infection. We accounted for the effects of age, BCG vaccination, and HIV infection. Additionally, we tested sensitivity to key structural assumptions by repeating all analyses without variation in BCG efficacy by latitude. Findings: The median number of children estimated to be sharing a household with an individual with infectious tuberculosis in 2010 was 15319701 (IQR 13766297-17061821). In 2010, the median number of Mycobacterium tuberculosis infections in children was 7591759 (5800053-9969780), and 650977 children (424871-983118) developed disease. Cumulative exposure meant that the median number of children with latent infection in 2010 was 53234854 (41111669-68959804). The model suggests that 35% (23-54) of paediatric cases of tuberculosis in the 15 countries reporting notifications by age in 2010 were detected. India is predicted to account for 27% (22-33) of the total burden of paediatric tuberculosis in the 22 countries. The predicted proportion of tuberculosis burden in children for each country correlated with incidence, varying between 4% and 21%. Interpretation: Our model has shown that the incidence of paediatric tuberculosis is higher than the number of notifications, particularly in young children. Estimates of current household exposure and cumulative infection suggest an enormous opportunity for preventive treatment. Funding: UNITAID and the US Agency for International Development. © 2014 Dodd et al. Open Access article distributed under the terms of CC BY.


Ginsberg A.M.,Global Alliance for TB Drug Development
Drugs | Year: 2010

Tuberculosis (TB) drug research and development efforts have resurged in the past 10 years to meet urgent medical needs, but enormous challenges remain. These urgent needs are largely driven by the current long and arduous multidrug regimens, which have significant safety, tolerability and compliance issues; rising and disturbing rates of multidrug- and extensively drug-resistant TB; the existence of approximately 2 billion individuals already latently infected with Mycobacterium tuberculosis, the causative pathogen of TB; and a global TB-HIV co-epidemic. Stakeholders in TB drug development are moving to enable and streamline development and registration of novel, multidrug treatment regimens, comprised of multiple new chemical entities with novel mechanisms of action that do not demonstrate cross-resistance to current first- and second-line TB drugs. Ideally, these new regimens will ultimately provide a short, simple treatment suitable for essentially all TB patients, whether sensitive or resistant to the current anti-TB agents, whether HIV-positive or -negative, and irrespective of patient age.This article reviews the challenges faced by those trying to develop these novel regimens and the key agents currently in clinical testing for TB; the latter are organized for discussion into three categories: (i) novel drugs (TMC207, SQ109, sudoterb LL3858); (ii) present first-line TB drugs being re-evaluated to optimize their efficacy (rifampicin, rifapentine); and (iii) currently licensed drugs for other indications and 'next-generation' compounds of the same chemical class being repurposed for TB (gatifloxacin and moxifloxacin; linezolid, PNU100480 and AZD5847; metronidazole, OPC-67683 and PA-824). © 2010 Adis Data Information BV. All rights reserved.


Ginsberg A.M.,Global Alliance for TB Drug Development
Tuberculosis | Year: 2010

Tuberculosis (TB) drug development has made substantial progress in the past decade. There are currently at least ten drugs being evaluated in clinical trials. Some belong to chemical classes already employed in first- or second-line treatment regimens and are being explored for more optimized use at higher doses or in new drug combinations (rifamycins, fluoroquinolones and oxazolidinones), while others represent potential novel members of the TB drug arsenal, killing Mycobacterium tuberculosis through previously untried mechanisms of action (nitroimidazoles, diarylquinolines, ethylene diamines and pyrroles). The typical challenges of drug development are augmented in TB by the complexity of the disease, the requirement for multi-drug regimens, the relative lack of TB drug development for the past several decades, and inadequate resources being brought to bear despite the urgency of the global medical need. Yet in the face of these challenges, for the first time in history, there is a robust enough pipeline of drugs in development to potentially enable identification of a novel, three-drug regimen capable of curing patients in three months or less, whether they are infected with a strain of M. tuberculosis sensitive or resistant to the current first and second-line drugs. Realizing this potential will require innovation, persistence, cooperation and resources. A fine balance will need to be achieved between protecting novel drugs so that resistance to them doesn't develop and ensuring the regimens are low in cost, readily available, and adopted by healthcare systems and providers. © 2010 Elsevier Ltd. All rights reserved.


Patent
Global Alliance For Tb Drug Development and Astrazeneca | Date: 2014-07-10

The invention provides compounds of formula (I) and methods of treating a Mycobacterium infection or tuberculosis, or inhibiting DprE1 with the same.


Patent
Global Alliance For Tb Drug Development | Date: 2010-07-30

The current invention pertains to nitroimidazooxazine and nitroimidazooxazole analogues, their methods of preparation, and uses of the compounds as treatment for Mycobacterium tuberculosis, for use as anti-tubercular drugs, for use as anti-protozoal agents with unexpectedly high potency against Trypanosoma cruzi or Leishmania donovani, and for the treatment of other microbial infections.


Patent
Institute Of Materia Medica and Global Alliance For Tb Drug Development | Date: 2011-06-28

The present invention relates to riminophenazines having heteroaromatic substitutions, including those with 2-heteroaryl-amino substituents, to their preparation, and to their use as drugs for treating Mycobacterium tuberculosis and other microbial infections, either alone or in combination with other anti-infective treatments.


Patent
Global Alliance For Tb Drug Development | Date: 2014-05-01

The present invention relates to riminophenazines having heteroaromatic substitutions, including those with 2-heteroaryl-amino substituents, to their preparation, and to their use as drugs for treating Mycobacterium tuberculosis and other microbial infections, either alone or in combination with other anti-infective treatments. A general representation of the 2-(heteroaryl)amino-riminophenazines is shown below.


Patent
Global Alliance For Tb Drug Development | Date: 2010-07-30

The present invention relates to novel nitroimidazooxazines, to their preparation, and to their use as drugs for treating Mycobacterium tuberculosis and other microbial infections, either alone or in combination with other anti-infective treatments.

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