The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Kate Zhong - One of the best experts on this subject based on the ideXlab platform.
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alzheimer s disease Drug Development pipeline 2019
Alzheimer's & Dementia: Translational Research & Clinical Interventions, 2019Co-Authors: Jeffrey L Cummings, Garam Lee, Aaron Ritter, Marwan N Sabbagh, Kate ZhongAbstract:Abstract Introduction Alzheimer's disease (AD) has few available treatments, and there is a high rate of failure in AD Drug Development programs. Study of the AD Drug Development pipeline can provide insight into the evolution of Drug Development and how best to optimize Development practices. Methods We reviewed clinicaltrials.gov and identified all pharmacologic AD trials of all agents currently being developed for treatment of AD. Results There are 132 agents in clinical trials for the treatment of AD. Twenty-eight agents are in 42 phase 3 trials; 74 agents are in 83 phase 2 trials; and 30 agents are in 31 phase 1 trials. There is an increase in the number of agents in each phase compared with that in the 2018 pipeline. Nineteen agents in trials target cognitive enhancement, and 14 are intended to treat neuropsychiatric and behavioral symptoms. There are 96 agents in disease modification trials; of these, 38 (40%) have amyloid as the primary target or as one of several effects. Eighteen of the antiamyloid agents are small molecules, and 20 are monoclonal antibodies or biological therapies. Seven small molecules and ten biologics have tau as a primary or combination target (18%). Amyloid is the most common specific target in phase 3 and phase 2 disease modification trials. Novel biomarkers (e.g., neurofilament light), new outcomes (e.g., AD Composite Score [ADCOMS]), enrollment of earlier populations, and innovative trial designs (e.g., Bayesian adaptive designs) are new features in recent clinical trials. Discussion Drug Development continues robustly at all phases despite setbacks in several programs in the recent past. Continuing unmet needs require a commitment to growing and accelerating the pipeline.
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alzheimer s disease Drug Development pipeline 2018
Alzheimer's & Dementia: Translational Research & Clinical Interventions, 2018Co-Authors: Jeffrey L Cummings, Garam Lee, Aaron Ritter, Kate ZhongAbstract:Abstract Introduction Treatments for Alzheimer's disease (AD) are needed due to the growing number of individuals with preclinical, prodromal, and dementia forms of AD. Drug Development for AD therapies can be examined by inspecting the Drug Development pipeline as represented on clinicaltrials.gov . Methods Clinicaltrials.gov was assessed as of January 30, 2018 to determine AD therapies represented in phase I, phase II, and phase III. Results There are 112 agents in the current AD treatment pipeline. There are 26 agents in 35 trials in phase III, 63 agents in 75 trials in phase II, and 23 agents in 25 trials in phase I. A review of the mechanisms of actions of the agents in the pipeline shows that 63% are disease-modifying therapies, 22% are symptomatic cognitive enhancers, and 12% are symptomatic agents addressing neuropsychiatric and behavioral changes. Trials in phase III are larger and longer than phase II or phase I trials, particularly those involving disease-modifying agents. Comparison with the 2017 pipeline shows that there are four new agents in phase III, 14 in phase II, and eight in phase I. Inspection of the use of biomarkers as revealed on clinicaltrials.gov shows that amyloid biomarkers are used as entry criterion in 14 phase III disease-modifying agent trials and 17 disease-modifying agent trials in phase II. Twenty-one trials of disease-modifying agents in phase II did not require biomarker confirmation for AD at trial entry. Discussion The AD Drug Development pipeline is slightly larger in 2018 than in 2017. Trials increasingly include preclinical and prodromal populations. There is an increase in nonamyloid mechanisms of action for Drugs in earlier phases of Drug Development. Biomarkers are increasingly used in AD Drug Development but are not used uniformly for AD diagnosis confirmation.
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alzheimer s disease Drug Development pipeline 2017
Alzheimer's & Dementia: Translational Research & Clinical Interventions, 2017Co-Authors: Jeffrey L Cummings, Garam Lee, Aaron Ritter, Travis Mortsdorf, Kate ZhongAbstract:Abstract Introduction There is an urgent need to develop new treatments for Alzheimer's disease (AD) and to understand the Drug Development process for new AD therapies. Methods We assessed the agents in the AD pipeline as documented in clinicaltrials.gov for phase I, phase II, and phase III, accessed 1/5/2017. Results There are 105 agents in the AD treatment Development pipeline, of which 25 agents are in 29 trials in phase I, 52 agents are in 68 trials in phase II, and 28 agents are in 42 trials in phase III. Seventy percent of Drugs in the AD pipeline are disease-modifying therapies (DMTs). Fourteen percent are symptomatic cognitive enhancers, and 13% are symptomatic agents addressing neuropsychiatric and behavioral changes (2% have undisclosed mechanisms). Most trials are sponsored by the biopharmaceutical industry. Trials include patients with preclinical AD (cognitively normal with biomarker evidence of AD), prodromal AD (mild cognitive symptoms and biomarker evidence of AD), and AD dementia. Biomarkers are included in many Drug Development programs particularly those for DMTs. Thirteen of 46 phase II DMT trials have amyloid imaging as an entry criterion, and 10 of 28 phase III trials incorporate amyloid imaging for diagnosis and entry. A large number of participants are needed for AD clinical trials; in total, 54,073 participants are required for trials spanning preclinical AD to AD dementia. When compared with the 2016 pipeline, there are eight new agents in phase I, 16 in phase II, and five in phase III. Discussion The AD Drug Development pipeline has 105 agents divided among phase I, phase II, and phase III. The trials include a wide range of clinical trial populations, many mechanisms of action, and require a substantial number of clinical trial participants. Biomarkers are increasingly used in patient identification and as outcome measures, particularly in trials of DMTs.
Le N Novere - One of the best experts on this subject based on the ideXlab platform.
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the promises of quantitative systems pharmacology modelling for Drug Development
Computational and structural biotechnology journal, 2016Co-Authors: Vincent Knightschrijver, Vijayalakshmi Chelliah, Lourdes Cucurullsanchez, Le N NovereAbstract:Recent growth in annual new therapeutic entity (NTE) approvals by the U.S. Food and Drug Administration (FDA) suggests a positive trend in current research and Development (R&D) output. Prior to this, the cost of each NTE was considered to be rising exponentially, with compound failure occurring mainly in clinical phases. Quantitative systems pharmacology (QSP) modelling, as an additional tool in the Drug discovery arsenal, aims to further reduce NTE costs and improve Drug Development success. Through in silico mathematical modelling, QSP can simulate Drug activity as perturbations in biological systems and thus understand the fundamental interactions which drive disease pathology, compound pharmacology and patient response. Here we review QSP, pharmacometrics and systems biology models with respect to the diseases covered as well as their clinical relevance and applications. Overall, the majority of modelling focus was aligned with the priority of Drug-discovery and clinical trials. However, a few clinically important disease categories, such as Immune System Diseases and Respiratory Tract Diseases, were poorly covered by computational models. This suggests a possible disconnect between clinical and modelling agendas. As a standard element of the Drug discovery pipeline the uptake of QSP might help to increase the efficiency of Drug Development across all therapeutic indications.
Jerome T Mettetal - One of the best experts on this subject based on the ideXlab platform.
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systems pharmacology to predict Drug safety in Drug Development
European Journal of Pharmaceutical Sciences, 2016Co-Authors: Mirjam N Trame, Konstantinos Iliouris, Lawrence J Lesko, Jerome T MettetalAbstract:Abstract Ensuring that Drugs are safe and effective is a very high priority for Drug Development and the US Food and Drug Administration review process. This is especially true today because of faster approval times and smaller clinical trials, especially in oncology and rare diseases. In light of these trends, systems pharmacology is seen as an essential strategy to understand and predict adverse Drug events during Drug Development by analyzing interactions between Drugs and multiple targets rather than the traditional “one-Drug-one-target” approach. This commentary offers an overview of the current trends and challenges of using systems pharmacology to reduce the risks of unintended adverse events.
James M Byrne - One of the best experts on this subject based on the ideXlab platform.
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fda public workshop summary advancing animal models for antibacterial Drug Development
Antimicrobial Agents and Chemotherapy, 2020Co-Authors: James M Byrne, Ursula Waack, Edward A Weinstein, Abhay Joshi, Simone M Shurland, Dmitri Iarikov, Jurgen B Bulitta, Binh An DiepAbstract:The U.S. Food and Drug Administration (FDA) hosted a public workshop entitled "Advancing Animal Models for Antibacterial Drug Development" on March 5, 2020. The workshop mainly focused on models of pneumonia caused by Pseudomonas aeruginosa and Acinetobacter baumannii The program included discussions from academic investigators, industry, and U.S. government scientists. The potential use of mouse, rabbit, and pig models for antibacterial Drug Development was presented and discussed.
Leslie Z Benet - One of the best experts on this subject based on the ideXlab platform.
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the role of bcs biopharmaceutics classification system and bddcs biopharmaceutics Drug disposition classification system in Drug Development
Journal of Pharmaceutical Sciences, 2013Co-Authors: Leslie Z BenetAbstract:Biopharmaceutics Classification System and Biopharmaceutics Drug Distribution Classification System are complimentary, not competing, classification systems that aim to improve, simplify, and speed Drug Development. Although both systems are based on classifying Drugs and new molecular entities into four categories using the same solubility criteria, they differ in the criterion for permeability and have different purposes. Here, the details and applications of both systems are reviewed with particular emphasis of their role in Drug Development. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:34–42, 2013
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membrane transporters in Drug Development
Nature Reviews Drug Discovery, 2010Co-Authors: Kathleen M Giacomini, Shiewmei Huang, Donald J Tweedie, Leslie Z Benet, Kim L R Brouwer, Xiaoyan Chu, Amber Dahlin, Raymond Evers, Volker Fischer, Kathleen M HillgrenAbstract:Membrane transporters can be major determinants of the pharmacokinetic, safety and efficacy profiles of Drugs. This presents several key questions for Drug Development, including which transporters are clinically important in Drug absorption and disposition, and which in vitro methods are suitable for studying Drug interactions with these transporters. In addition, what criteria should trigger follow-up clinical studies, and which clinical studies should be conducted if needed. In this article, we provide the recommendations of the International Transporter Consortium on these issues, and present decision trees that are intended to help guide clinical studies on the currently recognized most important Drug transporter interactions. The recommendations are generally intended to support clinical Development and filing of a new Drug application. Overall, it is advised that the timing of transporter investigations should be driven by efficacy, safety and clinical trial enrolment questions (for example, exclusion and inclusion criteria), as well as a need for further understanding of the absorption, distribution, metabolism and excretion properties of the Drug molecule, and information required for Drug labelling.
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opportunities for integration of pharmacokinetics pharmacodynamics and toxicokinetics in rational Drug Development
Journal of Pharmaceutical Sciences, 1992Co-Authors: Carl C Peck, Jerry M Collins, Leslie Z Benet, William H Barr, Robert E Desjardins, Daniel E Furst, John G Harter, Gerhard Levy, Thomas Ludden, John H RodmanAbstract:This report derives from the conference on “The Integration of Pharmacokinetic, Pharmacodynamic and Toxicokinetic Principles in Rational Drug Development,” held on April 24–26, 1991 in Arlington, VA. The conference was sponsored by the American Association of Pharmaceutical Scientists, U.S. Food and Drug Administration and the American Society for Clinical Pharmacology and Therapeutics.
