CNS drug development – Phase III

2012 ◽  
pp. 92-99
Author(s):  
Judith Dunn ◽  
Penny Randall ◽  
Amir Kalali
Keyword(s):  
Drug Development ◽  
Phase Iii ◽  
Development Phase

Old Drugs with New Tricks; Paradigm in Drug Development Pipeline for Alzheimer’s Disease

2020 ◽  
Vol 20 ◽  
Author(s):  
Tanay Dalvi ◽  
Bhaskar Dewangan ◽  
Rudradip Das ◽  
Jyoti Rani ◽  
Suchita Dattatray Shinde ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drug Development ◽  
Molecular Targets ◽  
Drug Repurposing ◽  
Phase Iii ◽  
Complex Nature ◽  
New Drug ◽  
Development Pipeline ◽  
Old Drugs

: The most common reason behind dementia is Alzheimer’s disease (AD) and it is predicted to be the third lifethreatening disease apart from stroke and cancer for the geriatric population. Till now only four drugs are available in the market for symptomatic relief. The complex nature of disease pathophysiology and lack of concrete evidences of molecular targets are the major hurdles for developing new drug to treat AD. The the rate of attrition of many advanced drugs at clinical stages, makes the de novo discovery process very expensive. Alternatively, Drug Repurposing (DR) is an attractive tool to develop drugs for AD in a less tedious and economic way. Therefore, continuous efforts are being made to develop a new drug for AD by repursing old drugs through screening and data mining. For example, the survey in the drug pipeline for Phase III clinical trials (till February 2019) which has 27 candidates, and around half of the number are drugs which have already been approved for other indications. Although in the past the drug repurposing process for AD has been reviewed in the context of disease areas, molecular targets, there is no systematic review of repurposed drugs for AD from the recent drug development pipeline (2019-2020). In this manuscript, we are reviewing the clinical candidates for AD with emphasis on their development history including molecular targets and the relevance of the target for AD.

Evolution of Digital Technologies and Use of Virtual Assistants in Drug Development

2019 ◽  
pp. 1-20
Author(s):  
Manu Venugopal
Keyword(s):  
Drug Development ◽  
Digital Health ◽  
Critical Role ◽  
Life Sciences ◽  
Digital Technologies ◽  
Development Phase ◽  
Health Technologies ◽  
Daunting Task ◽  
The World

The drug development phase is one of the most time-consuming and expensive stages in the lifecycle of a drug. Marred by patent expirations, price regulations, complexities in disease conditions, life sciences companies are facing a daunting task to bring new molecular entities into the market. Digital health technologies are playing a critical role in addressing some of the challenges faced during drug development. In this chapter, the author talks about the challenges and key trends in the world of drug development, use of new digital health technologies, and the future of drug development. As an example, the author dives into a specific case study on the use of virtual assistants in clinical trials and the benefits of its usage on patients, healthcare professionals, and life sciences companies.

Activity of gemcitabine in direct patient-derived xenografts and clinical outcome: Validation of an in vivo model for drug development

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4528-4528
Author(s):  
M. Hidalgo ◽  
I. Garrido-Laguna ◽  
M. Uson ◽  
E. De Oliveira ◽  
R. Schulick ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Outcome ◽  
Drug Development ◽  
Nude Mice ◽  
Median Overall Survival ◽  
Response Rate ◽  
Phase Iii ◽  
Adjuvant Setting ◽  
Metastatic Setting

4528 Background: Novel drugs are urgently needed for pancreatic ductal adenocarcinoma (PDA). Current preclinical models may not recapitulate the biology of human cancers. Direct xenografts have the potential to better represent the biology of human cancer. We have completed a clinical trial in which surgically resected PDAs were xenografted into nude mice thus generating an in vivo platform for drug development and biomarker identification. Methods: PDAs resected at Johns Hopkins Hospital are implanted into nude mice. From November 2005 to December 2008, 240 patients were consented, 236 operated, 102 were resectable PDAs thus fulfilling the inclusion criteria. 104 patients had other histologies and 34 were unresectable PDAs. Xenografted tumors were treated with gemcitabine and the activity in the xenograft correlated with patient clinical outcome. Results: Out of these 102 cases, 77 were xenografted, 53 were engrafted and reached the treatment phase. 35 out of the 53 originator patients were clinically treated with gemcitabine. The median overall survival of resected patients was 646 days (similar to 660 days from CONKO-001 trial). Patients whose carcinomas engrafted had a shorter median overall survival (319 vs. 728 days, p=0.002), probably reflecting a more aggressive tumor biology in the engrafted group. The response rate of gemcitabine in xenografts based on RECIST criteria was 8% (similar to response rate to gemcitabine in phase III trial by Moore et al.). In the adjuvant setting, the median disease free survival (DFS) was significantly longer in those patients predicted as sensitive by the xenograft model (568 vs. 286 days, p=0.037). In the metastatic setting, the median time to progression (TTP) was longer in those patients predicted as sensitive by the model (126 vs. 73 days) though this difference was not statistically significant. Overall the correlation between gemcitabine activity in this model and clinical outcome as measured by DFS was 0.71 in the subgroup of patients whose xenografts had a TGI lower than -10%. Conclusions: This preclinical model predicts gemcitabine outcome in the clinic in the adjuvant setting. Further studies to analyze the causes of shorter survival in patients whose PDA engrafted are warranted. No significant financial relationships to disclose.

scholarly journals Inhibiting Mycobacterium tuberculosis within and without

2016 ◽  
Vol 371 (1707) ◽  
pp. 20150506 ◽  
Author(s):  
Stewart T. Cole
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Drug Development ◽  
Cholesterol Metabolism ◽  
Treatment Options ◽  
Scientific Progress ◽  
Phase Iii ◽  
Phase Iii Trials ◽  
Shorten Treatment Duration ◽  
Drug Resistant Strains

Tuberculosis remains a scourge of global health with shrinking treatment options due to the spread of drug-resistant strains of Mycobacterium tuberculosis . Intensive efforts have been made in the past 15 years to find leads for drug development so that better, more potent drugs inhibiting new targets could be produced and thus shorten treatment duration. Initial attempts focused on repurposing drugs that had been developed for other therapeutic areas but these agents did not meet their goals in clinical trials. Attempts to find new lead compounds employing target-based screens were unsuccessful as the leads were inactive against M. tuberculosis . Greater success was achieved using phenotypic screening against live tubercle bacilli and this gave rise to the drugs bedaquiline, pretomanid and delamanid, currently in phase III trials. Subsequent phenotypic screens also uncovered new leads and targets but several of these targets proved to be promiscuous and inhibited by a variety of seemingly unrelated pharmacophores. This setback sparked an interest in alternative screening approaches that mimic the disease state more accurately. Foremost among these were cell-based screens, often involving macrophages, as these should reflect the bacterium's niche in the host more faithfully. A major advantage of this approach is its ability to uncover functions that are central to infection but not necessarily required for growth in vitro . For instance, inhibition of virulence functions mediated by the ESX-1 secretion system severely attenuates intracellular M. tuberculosis , preventing intercellular spread and ultimately limiting tissue damage. Cell-based screens have highlighted the druggability of energy production via the electron transport chain and cholesterol metabolism. Here, I review the scientific progress and the pipeline, but warn against over-optimism due to the lack of industrial commitment for tuberculosis drug development and other socio-economic factors. This article is part of the themed issue ‘The new bacteriology’.

Using Early Drug Development Data to Design Phase III Trials

1991 ◽  
Vol 25 (3) ◽  
pp. 335-344 ◽  
Author(s):  
James F. Ward ◽  
Ronald V. Nardi
Keyword(s):  
Drug Development ◽  
Phase Iii ◽  
Design Phase ◽  
Development Data ◽  
Phase Iii Trials ◽  
Early Drug

scholarly journals Drug Development in Alzheimer’s Disease—The Role of Default Mode Network Assessment in Phase II

US Neurology ◽  
2017 ◽  
Vol 13 (02) ◽  
pp. 67 ◽  
Author(s):  
Jeffrey Cummings ◽  
Kate Zhong ◽  
Dietmar Cordes ◽  
◽  
◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drug Development ◽  
Phase Ii ◽  
Default Mode Network ◽  
Phase Iii ◽  
Human Cognition ◽  
Default Mode ◽  
Disease Modifying Agents ◽  
New Treatments

Alzheimer’s disease (AD) is rapidly becoming more common as the global population ages. New treatments are needed and new approaches to drug development are warranted. The phase II challenge for AD treatment development programs is how to provide proof-of-concept (POC) of the candidate agent without a large long trial equivalent to phase III. We propose that the available data support measures of the default mode network (DMN) using functional magnetic resonance imaging (fMRI) as demonstrating the effect of treatment on cognitive circuits critical to human cognition. Improved DMN function with symptomatic cognitive enhancing agents or decreased deterioration of DMN function compared to placebo in trials of disease-modifying agents would support POC and allow progression to phase III with greater confidence.

Sign in / Sign up

Export Citation Format

Share Document