Alzheimer's drug-development pipeline: 2016.
Ontology highlight
ABSTRACT:
SUBMITTER: Cummings J
PROVIDER: S-EPMC5651348 | biostudies-literature | 2016 Nov
REPOSITORIES: biostudies-literature
Publications
Alzheimer's drug-development pipeline: 2016.
Cummings Jeffrey J Morstorf Travis T Lee Garam G
Alzheimer's & dementia (New York, N. Y.) 20160817 4
<h4>Background</h4>Alzheimer's disease (AD) is growing in frequency and new therapies are urgently needed.<h4>Methods</h4>We assessed clinicaltrials.gov (accessed 1-4-2016) to determine the number and characteristics of trials in phase I, phase II, and phase III for treatment of AD.<h4>Results</h4>There are currently 24 agents in 36 trials in phase III of AD drug development. Seven of these 24 agents are symptomatic cognitive-enhancing compounds, and 17 are disease-modifying treatments (DMTs). M ...[more]
Similar Datasets
Project description:Introduction:Alzheimer's disease (AD) is a growing public health concern affecting millions of patients worldwide and costing billions of dollars annually. We review the pipeline of drugs and biologics in clinical trials for the treatment of AD. We use the Common Alzheimer's and Related Dementias Research Ontology (CADRO) to classify treatment targets and mechanisms of action. We review our annual pipeline reports for the past 5 years to provide longitudinal insight into clinical trials and drug development for AD. Methods:We reviewed ClinicalTrials.gov as of February 27, 2020, and identified all trials of pharmacologic agents currently being developed for treatment of AD as represented on this widely used U.S. Food and Drug Administration registry. Results:There are 121 agents in clinical trials for the treatment of AD. Twenty-nine agents are in 36 Phase 3 trials, 65 agents are in 73 Phase 2 trials, and 27 agents are in 27 Phase 1 trials. Twelve agents in trials target cognitive enhancement and 12 are intended to treat neuropsychiatric and behavioral symptoms. There are 97 agents in disease modification trials. Compared to the 2019 pipeline, there is an increase in the number of disease-modifying agents targeting pathways other than amyloid or tau. Discussion:The 2020 pipeline has innovations in clinical trials and treatment targets that provide hope for greater success in AD drug development programs. Review of clinical trials over the past 5 years show that there is progressive emphasis on non-amyloid targets, including candidate treatments for inflammation, synapse and neuronal protection, vascular factors, neurogenesis, and epigenetic interventions. There has been a marked growth in repurposed agents in the pipeline.
| S-EPMC7364858 | biostudies-literature
Project description: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.
| S-EPMC6021548 | biostudies-literature
Project description:IntroductionAlzheimer'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.MethodsWe reviewed clinicaltrials.gov and identified all pharmacologic AD trials of all agents currently being developed for treatment of AD.ResultsThere 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.DiscussionDrug 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.
| S-EPMC6617248 | biostudies-literature
Project description: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.
| S-EPMC5651419 | biostudies-literature
Project description:IntroductionAlzheimer's disease (AD) represents a global health crisis. Treatments are needed to prevent, delay the onset, slow the progression, improve cognition, and reduce behavioral disturbances of AD. We review the current clinical trials and drugs in development for the treatment of AD.MethodsWe searched the governmental website clinicaltrials.gov where are all clinical trials conducted in the United States must be registered. We used artificial intelligence (AI) and machine learning (ML) approaches to ensure comprehensive detection and characterization of trials and drugs in development. We use the Common Alzheimer's Disease Research Ontology (CADRO) to classify drug targets and mechanisms of action of drugs in the pipeline.ResultsAs of January 25, 2022 (index date for this study) there were 143 agents in 172 clinical trials for AD. The pipeline included 31 agents in 47 trials in Phase 3, 82 agents in 94 trials in Phase 2, and 30 agents in 31 trials in Phase 1. Disease-modifying therapies represent 83.2% of the total number of agents in trials; symptomatic cognitive enhancing treatments represent 9.8% of agents in trials; and drugs for the treatment of neuropsychiatric symptoms comprise 6.9%. There is a diverse array of drug targets represented by agents in trials including nearly all CADRO categories. Thirty-seven percent of the candidate agents in the pipeline are repurposed drugs approved for other indications. A total of 50,575 participants are needed to fulfill recruitment requirements for all currently active clinical trials.DiscussionThe AD drug development pipeline has agents representing a substantial array of treatment mechanisms and targets. Advances in drug design, outcome measures, use of biomarkers, and trial conduct promise to accelerate the delivery of new and better treatments for patients with AD.HighlightsThere are 143 drugs in the current Alzheimer's disease (AD) drug development pipeline.Disease-modifying therapies represent 83.2% of the candidate treatments.Current trials require 50,575 participants who will donate 3,878,843 participant-weeks to clinical trials.The biopharmaceutical industry sponsors 50% of all clinical trials including 68% of Phase 3 trials.Sixty-three percent of Phase 3 trials and 46% of Phase 2 trials include non-North American clinical trial site locations indicating the global ecosystem required for AD drug development.
| S-EPMC9066743 | biostudies-literature
Project description:IntroductionThe number of individuals worldwide with Alzheimer's disease (AD) is growing at a rapid rate. New treatments are urgently needed. We review the current pipeline of drugs in clinical trials for the treatment of AD.MethodsWe interrogated ClinicalTrials.gov, the federal registry of clinical trials to identify drugs in trials.ResultsThere are 126 agents in 152 trials assessing new therapies for AD: 28 treatments in Phase 3 trials, 74 in Phase 2, and 24 in Phase 1. The majority of drugs in trials (82.5%) target the underlying biology of AD with the intent of disease modification; 10.3% are putative cognitive enhancing agents; and 7.1% are drugs being developed to reduce neuropsychiatric symptoms.DiscussionThis pipeline analysis shows that target biological processes are more diversified, biomarkers are more regularly used, and repurposed agents are being explored to determine their utility for the treatment of AD.
| S-EPMC8145448 | biostudies-literature
Project description:IntroductionDrugs that prevent the onset, slow progression, or improve cognitive and behavioral symptoms of Alzheimer's disease (AD) are needed.MethodsWe searched ClinicalTrials.gov for all current Phase 1, 2 and 3 clinical trials for AD and mild cognitive impairment (MCI) attributed to AD. We created an automated computational database platform to search, archive, organize, and analyze the derived data. The Common Alzheimer's Disease Research Ontology (CADRO) was used to identify treatment targets and drug mechanisms.ResultsOn the index date of January 1, 2023, there were 187 trials assessing 141 unique treatments for AD. Phase 3 included 36 agents in 55 trials; 87 agents were in 99 Phase 2 trials; and Phase 1 had 31 agents in 33 trials. Disease-modifying therapies were the most common drugs comprising 79% of drugs in trials. Twenty-eight percent of candidate therapies are repurposed agents. Populating all current Phase 1, 2, and 3 trials will require 57,465 participants.DiscussionThe AD drug development pipeline is advancing agents directed at a variety of target processes.HighlightsThere are currently 187 trials assessing 141 drugs for the treatment of Alzheimer's disease (AD).Drugs in the AD pipeline address a variety of pathological processes.More than 57,000 participants will be required to populate all currently registered trials.
| S-EPMC10210334 | biostudies-literature
Project description:BackgroundTreatments are needed to address the growing prevalence of Alzheimer's disease (AD). Clinical trials have failed to produce any AD drugs for Food and Drug Administration (FDA) approval since 2003, and the pharmaceutical development process is both time-consuming and costly. Drug repurposing provides an opportunity to accelerate this process by investigating the AD-related effects of agents approved for other indications. These drugs have known safety profiles, pharmacokinetic characterization, formulations, doses, and manufacturing processes.MethodsWe assessed repurposed AD therapies represented in Phase I, Phase II, and Phase III of the current AD pipeline as registered on ClinicalTrials.gov as of February 27, 2020.ResultsWe identified 53 clinical trials involving 58 FDA-approved agents. Seventy-eight percent of the agents in trials had putative disease-modifying mechanisms of action. Of the repurposed drugs in the pipeline 20% are hematologic-oncologic agents, 18% are drugs derived from cardiovascular indications, 14% are agents with psychiatric uses, 12% are drug used to treat diabetes, 10% are neurologic agents, and the remaining 26% of drugs fall under other conditions. Intellectual property strategies utilized in these programs included using the same drug but altering doses, routes of administration, or formulations. Most repurposing trials were supported by Academic Medical Centers and were not funded through the biopharmaceutical industry. We compared our results to a European trial registry and found results similar to those derived from ClinicalTrials.gov.ConclusionsDrug repurposing is a common approach to AD drug development and represents 39% of trials in the current AD pipeline. Therapies from many disease areas provide agents potentially useful in AD. Most of the repurposed agents are generic and a variety of intellectual property strategies have been adopted to enhance their economic value.
| S-EPMC7433208 | biostudies-literature
Project description:Cystic fibrosis is a genetic disease that results in progressive multi-organ manifestations with predominance in the respiratory and gastrointestinal systems. The significant morbidity and mortality seen in the CF population has been the driving force urging the CF research community to further advance treatments to slow disease progression and, in turn, prolong life expectancy. Enormous strides in medical advancements have translated to improvement in quality of life, symptom burden, and survival; however, there is still no cure. This review discusses the most current mainstay treatments and anticipated therapeutics in the CF drug development pipeline within the mechanisms of mucociliary clearance, anti-inflammatory and anti-infective therapies, restoration of the cystic fibrosis transmembrane conductance regulator (CFTR) protein (also known as highly effective modulator therapy (HEMT)), and genetic therapies. Ribonucleic acid (RNA) therapy, gene transfer, and gene editing are being explored in the hopes of developing a treatment and potential cure for people with CF, particularly for those not responsive to HEMT.
| S-EPMC10532558 | biostudies-literature
Project description:Tuberculosis now ranks as the leading cause of death in the world due to a single infectious agent. Current standard of care treatment can achieve very high cure rates for drug-sensitive disease but requires a 6-month duration of chemotherapy. Drug-resistant disease requires significantly longer treatment durations with drugs associated with a higher risk of adverse events. Thus, there is a pressing need for a drug regimen that is safer, shorter in duration and superior to current front-line chemotherapy in terms of efficacy. The TB drug pipeline contains several candidates that address one or more of the required attributes of chemotherapeutic regimens that may redefine the standard of care of this disease. Several new drugs have been reported and novel targets have been identified allowing regimens containing new compounds to trickle into clinical studies. Furthermore, a recent paradigm-shift in understanding the pharmacokinetics of anti-tubercular drugs is revolutionizing the way we select compounds for clinical progression.
| S-EPMC6204086 | biostudies-literature