Clinical Trials Of New Drugs Research Articles

A Review on Canine and Human Soft Tissue Sarcomas: New Insights on Prognosis Factors and Treatment Measures.

Soft tissue sarcomas (STSs) represent a diverse group of tumors arising from mesenchymal cells, affecting both humans and animals, including dogs. Although STSs represent a class of rare tumors, especially in humans, they pose significant clinical challenges due to their potential for local recurrence and distant metastasis. Dogs, as a model for human STSs, offer several advantages, including exposure to similar environmental risk factors, genetic diversity among breeds, and the spontaneous development of tumors. Furthermore, canine tumors closely mimic the heterogeneity and complexity of human tumors, making them valuable for research into disease progression and treatment effectiveness. Current treatment approaches for STSs in both dogs and humans primarily involve surgery, radiation therapy, and chemotherapy, with treatment decisions based on tumor characteristics and patient factors. However, the development of novel therapeutic strategies is essential, given the high failure rate of new drugs in clinical trials. To better design new tailored treatments, comprehension of the tumor microenvironment (TME) is fundamental, since it plays a crucial role in STS initiation and progression by modulating tumor behavior, promoting angiogenesis, and suppressing immune responses. Notably, TME features include cancer-associated fibroblasts (CAFs), extracellular matrix (ECM) alterations, and tumor-associated macrophages (TAMs) that, depending on their polarization state, can affect immune responses and thus the patient's prognosis. In this review, new therapeutical approaches based on immunotherapy will be deeply explored as potential treatment options for both dogs and humans with STSs. In conclusion, this review provides an overview of the current understanding of STSs in dogs and humans, emphasizing the importance of the TME and potential treatment strategies.

What has antifibrotic therapy changed for patients with idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic interstitial lung disease of unknown cause. IPF is characterized by excessive production and deposition of extracellular matrix components, which lead to irreversible violations of the architectonics of lung tissue and loss of function. Without treatment, the average survival rate of patients after diagnosis does not exceed 3–5 years. However, published observations report improved survival over the past decade, due to the advent of antifibrotic drugs and earlier diagnosis. The benefits of antifibrotic therapy include a slower rate of reduction in forced lung capacity (FVC) and a reduction in mortality. Pirfenidone and nantedanib are the only currently approved antifibrotic drugs for the treatment of IPF. Several generic drugs with the INN pirfenidone are registered on the Russian market, including the drug PIRFASPEC® (267 mg capsules). Their efficacy and safety have been demonstrated both in randomized clinical trials and in real clinical practice studies. IPF patient registries, which have been maintained in many countries since 2010, provide additional information regarding the progression of the disease, the effectiveness of therapy, and the frequency of adverse events. Although they have a different mechanism of action and safety profile, their effectiveness in slowing the decline of FVC and reducing the risk of mortality over time is similar. However, IPF is still characterized by progressive shortness of breath and poor prognosis, as treatment can only delay the progression of IPF and cannot stop or reverse the damage. Although clinical trials of new drugs for the treatment of IPF are currently underway, no other drugs have yet been approved in the Russian Federation.

Adapting a prescreening program from VHIO to match molecular alterations in over 10,000 patients' tumors with targeted agents and immunotherapies in early clinical trials.

e23071 Background: VHIO's Molecular Prescreening Program (MPP) began in 2010 to catalyze precision medicine at the institution. Over the last decade, this program has provided access to advanced molecular diagnostics to more than 10,000 cancer patients (pts) and is critical in matching targeted therapeutic approaches to clinical trials (CTs). Here we report the clinical utility of our program given the evolving molecular testing landscape and trends in drug development. Methods: We assess the adoption and impact of the VHIO’s MPP in CTs recruitment. All tests were developed in-house: a. from 2010 to 2014 we used formalin fixed paraffin embedded tumor samples to test for hotspot mutations (Sequenom, 20 oncogenes) plus FISH/IHC of selected markers; b. from 2015 to 2017 we moved to a amplicon-based NGS panel (MiSeq, 61 genes), a copy number alteration (CNA) panel (Nanostring, 44 genes) and a fusion + gene expression assay (Nanostring, 26 genes) with additional FISH/IHC in selected cases, including PDL1 and MSI status; c. since 2019, we use a custom capture-based NGS assay for mutations (mut), CNA and Tumor Mutation Burden (TMB) estimation (NextSeq, 435 genes); d. since 2022, we run a liquid biopsy panel in-house (Guardant360, technology transfer). Results: We found a stepwise increase in the MPP adoption, from 207 pts in 2010 to 1,965 pts in 2023, representing almost a tenfold increase. Most common tumours analysed were colorectal, lung, breast, gynaecologic, pancreato-biliary, and gastric. The number of CTs requiring biomarker match has increased from 13 in 2010 to more than 201 in 2023, the most frequent in the last year being HER2 (33), PDL1 (20), EGFR (17), RAS (15) and FGFR (9), MSI (9) and ALK (7). In 2023, 1,230 patients had broad tissue NGS panel, 1,235 were tested with IHC, 373 with fusions + expression assay and 991 with liquid biopsy. Inclusion rate in CTs with biomarker match has fluctuated between 13% and 19% in the past 5 years. Overall, close to 50% of these trial recruitments are with genomically-informed enrichment strategies and not mandatory inclusion criteria. On average, 20% of the patients were still enrolled in unmatched trials after molecular testing. Conclusions: The success of VHIO's MPP is related to agile innovation and clinical deployment of new technologies in a timely manner, critical for the development of new drugs in CTs. Biomarker matched trials evolved from a “few targets/ large populations” scenario to a complex situation with “many targets/ small populations”. Many pts benefit from enrichment strategies in Phase 1 CTs. The impact of the recent implementation of liquid biopsy and ongoing development of genomic + transcriptomic signatures will be closely monitored.

Сравнительный анализ адаптивности протоколов клинических исследований к пандемии COVID-19 нескольких спонсоров

The pandemic caused by the SARS-CoV-2 virus has put a huge strain on health systems around the world. Clinical trials of new drugs were also influenced by the pandemic, during which Sponsors came across a number of problems, including ensuring patient safety and maintaining the ability to obtain reliable data in the course of ongoing research. The purpose of this study was to compare the protocols of clinical trials of two Sponsors, approved by the Russian health authorities for three years, from 2017 to 2019, by their adaptability to the SARS-CoV-2 virus pandemic. 23 protocols and 51 amendments were studied in total. The amendments published in 2020 by both Sponsors underwent a comparative analysis to determine the degree of their influence by the pandemic. Statistical processing of the results was carried out using the correlation analysis. Conclusions were drawn about the Sponsors’ approach to clinical trial planning and establishing the safety margin of clinical trial protocols.

Abstract LB218: Advanced ex vivo platform for drug response analysis: Evaluating the potent effects of NMC-521 mAb on mouse-and patient-derived organotypic tumor spheroids

Abstract In response to the high failure rate of new drugs in clinical trials, we have developed an innovative organotypic tumor spheroids platform, designed to mitigate the risks associated with advancing drugs to clinical stages. Utilizing patient-derived organotypic tumor spheroids (PDOTS), this platform uniquely captures both the phenotype and genotype of individual patient tumor microenvironments. This approach not only enhances the precision of preclinical models but also bridges the gap between laboratory research and clinical applicability. In this study, we assess the effectiveness of the first-in-class monoclonal antibody NMC-521 (NomoCan Pharmaceuticals, NY) using our ex vivo platform. Targeting the novel cancer-specific antigen NMC-1, NMC-521 exhibited significant growth inhibition of CT-26 tumors in syngeneic BALB/c mice, reducing tumor size by approximately 55% compared to the control. Similarly, in ex vivo settings with freshly excised CT-26 tumors (n=18), NMC-521 demonstrated a dose-dependent cytotoxic effect, achieving about a 65% reduction in tumor viability with an effective dose (ED50) of 10 µg/ml. Further insights were gained into NMC-521's mechanism of action using our ex vivo platform. The drug’s ability to induce tumor cell death in CT26 ex vivo was significantly reversed (p<0.01) when co-treated with α-NKG2D but not α-CD8, indicating a critical role for natural killer (NK) cells in its therapeutic effect. Complementing these findings, our analyses on freshly excised patient tumors (n=15) corroborated the cytotoxic effects of this drug on colorectal cancer but not to the same magnitude as in the CT-26 model. Furthermore, unlike the syngeneic murine tumor model, the response rate was (8 of 15 responsive patient tumors. Gene expression profiling indicated that NK cell-associated RNAs were elevated in NMC-521 treated PDOTS. Additionally, combination therapy studies using NMC-521 and nivolumab within our platform mirrored murine in vivo results, enhancing our understanding of the drug's potential in clinical settings. Intriguingly, an observed elevation in IL-15 levels in patient tumors treated with NMC-521 suggests an increased presence of NK cell activity when compared to treatments with nivolumab. This research underscores the potential of our organotypic tumor spheroids platform as a transformative tool in cancer drug development, offering an accurate and patient-specific method to evaluate new therapies, thereby increasing the likelihood of successful translation from the laboratory to patient care. Citation Format: Amir Aref, Alyssa Martin, Hamidreza Aboulkheyr Es, Patryk Krzesaj, Victor Adler, Kirti Khardenavis, Ehsan Sarafraz-Yazdi, Michael A. Perricone. Advanced ex vivo platform for drug response analysis: Evaluating the potent effects of NMC-521 mAb on mouse-and patient-derived organotypic tumor spheroids [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB218.

Placebo and Nocebo Responses in Pharmacological Trials of Tic Disorders: A Meta-Analysis.

Clinical trials of new drugs for tic disorders (TD) often fail to yield positive results. Placebo and nocebo responses play a vital role in interpreting the outcomes of randomized controlled trials (RCTs), yet these responses in RCTs of TD remain unexplored. The aim was to assess the magnitude of placebo and nocebo responses in RCTs of pharmacological interventions for TD and identify influencing factors. A systematic search of the Embase, Medline, Cochrane Central Register of Controlled Trials, and PsycINFO databases was conducted. Eligible studies were RCTs that compared active pharmacological agents with placebos. Placebo response was defined as the change from baseline in TD symptom severity in the placebo group, and nocebo response as the proportion experiencing adverse events (AEs) in this group. Subgroup analysis and meta-regression were performed to explore modifying factors. Twenty-four trials involving 2222 participants were included in this study. A substantial placebo response in TD symptom severity was identified, with a pooled effect size of -0.79 (95% confidence interval [CI] -0.99 to -0.59; I2 = 67%). Forty-four percent (95% CI 27% to 63%; I2 = 92%) of patients experienced AEs while taking inert pills. Sample size, study design, and randomization ratio were correlated with changes in placebo and nocebo responses. There were considerable placebo and nocebo responses in TD clinical trials. These results are of great relevance for the design of future trials and for clinical practice in TD. PROSPERO registration ID CRD42023388397. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Inducing Cytotoxicity in Colon Cancer Cells and Suppressing Cancer Stem Cells by Dolasetron and Ketoprofen through Inhibition of RNA Binding Protein PUM1.

Clinical trials of new drugs often face a high failure rate of approximately 45 percent due to safety and toxicity concerns. Repurposing drugs with well-established safety profiles becomes crucial in addressing this challenge. Colon cancer ranks as the third most prevalent cancer and the second leading cause of cancer related mortality worldwide. This study focuses on the RNA-binding protein pumilio1 (PUM1), a member of the PUF family involved in post-transcriptional gene expression regulation. By utilizing molecular docking techniques and FDA-approved drugs, potential inhibitors against PUM1 were identified. Notably, dolasetron and ketoprofen demonstrated promising results, exhibiting strong binding affinity, hydrophobic interactions, and favorable chemical reactivity according to Conceptual-DFT calculations. Both compounds effectively reduced cell viability, with IC50 values of 150 µM and 175 µM, respectively and shows long term inhibitory effects as seen by reduced in number of colonies. Moreover, they exhibited inhibitory effects on colon cancer stem cells, as indicated by reduced colonospheroid size and numbers. Apoptosis is induced by these compounds and has triggered activation of executioner caspase 3/7 in HCT116 cells which is evident through a caspase 3/7 assay and AO/EB staining, while the non-toxic effect of these compounds was evident from viability against non-cancerous cell line and hemolysis assay. Additionally, the treatment group showed a significant decrease in PUM1 and cancer stem cell markers expression compared to the control group. In conclusion, this study highlights the potential of targeting PUM1 as a novel approach to colon cancer treatment. Dolasetron and ketoprofen demonstrate promise as effective anti-cancer and anti-cancer stem cell drugs, inducing apoptosis in colon cancer cells through inhibition of PUM1.

Alzheimer's disease and neuroinflammation: will new drugs in clinical trials pave the way to a multi-target therapy?

Despite extensive research, no disease-modifying therapeutic option, able to prevent, cure or halt the progression of Alzheimer's disease [AD], is currently available. AD, a devastating neurodegenerative pathology leading to dementia and death, is characterized by two pathological hallmarks, the extracellular deposits of amyloid beta (Aβ) and the intraneuronal deposits of neurofibrillary tangles (NFTs) consisting of altered hyperphosphorylated tau protein. Both have been widely studied and pharmacologically targeted for many years, without significant therapeutic results. In 2022, positive data on two monoclonal antibodies targeting Aβ, donanemab and lecanemab, followed by the 2023 FDA accelerated approval of lecanemab and the publication of the final results of the phase III Clarity AD study, have strengthened the hypothesis of a causal role of Aβ in the pathogenesis of AD. However, the magnitude of the clinical effect elicited by the two drugs is limited, suggesting that additional pathological mechanisms may contribute to the disease. Cumulative studies have shown inflammation as one of the main contributors to the pathogenesis of AD, leading to the recognition of a specific role of neuroinflammation synergic with the Aβ and NFTs cascades. The present review provides an overview of the investigational drugs targeting neuroinflammation that are currently in clinical trials. Moreover, their mechanisms of action, their positioning in the pathological cascade of events that occur in the brain throughout AD disease and their potential benefit/limitation in the therapeutic strategy in AD are discussed and highlighted as well. In addition, the latest patent requests for inflammation-targeting therapeutics to be developed in AD will also be discussed.

Research on the legal regulation of experimental medicine in China

The increasing number of clinical trials of new drugs in China has brought huge benefits to the society, but also implied huge risks. This is particularly evident in experimental medicine. Germany has achieved good results in regulating experimental medical behaviors through the model of legislative norms. China should learn from Germany's beneficial experience to promote the orderly development of experimental medical behavior in China. Specifically, the crime of illegal human experiment should be added to the criminal law; Adopt special legislation model to regulate experimental medical behavior; Establish a no fault medical liability system to share experimental medical risks;Absorb and learn from the relevant norms of the international community on human experiment.

Trend of clinical trials of new drugs for rare diseases in China in recent 10 years

BackgroundRare disease is a general term for a disease that affects a small number of people but recognized as a global public health priority. Governments worldwide are paying more and more attention to the academical research and drug investment of rare diseases. The conduct of rare disease clinical trials is still difficult, despite the promotion of government policies and the awakening of social consciousness. In this article, we outlined the characteristics and obstacles of clinical trials of rare diseases in China and expected to provide reference for subsequent clinical trials in this field.ResultsIn recent years, China has made some progress in clinical trials of rare diseases in the past 10 years. There were 481 clinical trials on rare diseases in total, covering more than 10 rare diseases with high incidence. Clinical trial applications on rare diseases for a total of 481 were submitted and with an average annual growth rate of 28.2% from 2013 to 2022. The number of clinical trial application for rare diseases in 2016 dramatically increased by 80% compared to 2015 due to the policy document issued by China for clinical research in rare diseases in 2015. Besides, about 70% of applications registering for clinical trials could recruit subjects as expected. Despite this, the number of clinical trials of rare diseases in China was less compared with the United States, Europe and Japan, and the types of infant drugs were limited to biological products and chemical drugs lacking other new treatments.ConclusionsEfforts have been made in recent years to develop clinical research on rare diseases in China. The number of clinical trials for rare diseases in China was growing steadily every year, which was inseparable from the support of the country, society and rare disease patients. Still, there was a large gap between China and other developed countries in this field and this merit further investigation.

Ethical Planning in Conducting a Research Project

Countries that still do not have a national normative document on research ethics, like most African and Latin American countries, have taken the Declaration of Helsinki as a reference for ethical guidance to researchers and members of ethics committees. However, the literature has shown that the latest revisions of this declaration have tended to favor the interests of central countries and their industries, mainly through the more flexible acceptance of greater risks and smaller benefits. Even when there are norms adequate to the reality of each country, the ethical planning of a research goes far beyond the simple bureaucratic fulfillment of the norms that guide the presentation of a protocol and a consent term to a research ethics committee. It presupposes an in-depth reflection on the methodological procedures themselves that will involve the participants and on the ways in which they interact with the socioeconomic and cultural contexts of these participants' daily lives. In developing countries, consideration of social vulnerability, especially with regard to poverty and low levels of education, is a central element in this planning. I intend to discuss this planning taking the three classic axes of research subject protection: obtaining consent, minimizing risks and maximizing benefits in their relationship with contexts of social vulnerability in three modalities of health research: those that handle information from identifiable subjects, such as clinical protocols; those using interviews and questionnaires; and clinical trials for new drugs.

MP21-10 SEX BIAS IN CONTEMPORARY CLINICAL DRUG TRIALS IN UROLOGY

You have accessJournal of UrologyCME1 Apr 2023MP21-10 SEX BIAS IN CONTEMPORARY CLINICAL DRUG TRIALS IN UROLOGY Andres Guillen Lozoya, Candace Granberg, Vidit Sharma, Patricio Gargollo, and Kevin Koo Andres Guillen LozoyaAndres Guillen Lozoya More articles by this author , Candace GranbergCandace Granberg More articles by this author , Vidit SharmaVidit Sharma More articles by this author , Patricio GargolloPatricio Gargollo More articles by this author , and Kevin KooKevin Koo More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003246.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Despite federal policies to foster equal representation of female and male participants, sex bias remains common in clinical trial enrollment, leading to underrepresentation of women among trial participants. The extent of sex bias in clinical trials in urology is not well characterized. This study aimed to evaluate enrollment rates by sex for clinical trials leading to new drug approvals in urology. METHODS: We retrospectively reviewed the US Food and Drug Administration database for new drug approvals for urological indications from 2016 through 2021. Published trials that supported these approvals were analyzed to determine enrollment rates of female participants. The sample was grouped and analyzed by demographic and clinical variables. To assess sex bias, we defined a “sex-matching ratio” as the proportion of female to male trial enrollees, where a ratio of 1.0 would indicate equal numbers of women and men. A ratio ≥0.9 was considered “optimal” based on prior published studies. RESULTS: Of a total of 20 trials supporting novel drugs in urology, 6 were excluded due to sex-specific conditions, leaving a total of 14 trials that enrolled 10,875 female and male participants. The clinical indications in the trials included urinary tract infection (4 trials, 29%), urothelial carcinoma (4 trials, 29%), renal cell carcinoma (1 trial,7%), and overactive bladder (1 trial, 7%). Women accounted for 43% of the total sample and had significantly less enrollment in trials for cancer indications; women were only 26% of enrollees in urothelial and renal cancer trials vs 45% in non-cancer trials (p<0.001). Five trials (36%) enrolled more women than men overall; however, the participants in these majority-women trials (3,215) only comprised 30% of total enrolled sample. In terms of sex bias, 7 of the trials (50%) achieved an optimal sex-matching ratio ≥0.9. Among the other 7 trials with suboptimal sex-matching ratios, 1 trial had a ratio of 0.75, while the remaining 6 trials had ratios <0.5 (range 0.26-0.42), indicating that women accounted for less than half the number of men in these trials. The total enrollees in the 7 trials with suboptimal sex-matching ratios was 6,728; of these, women (1,962) accounted for just 29% of the sample. CONCLUSIONS: Sex bias is common in contemporary clinical trials for new drugs in urology. In half the trials with the strongest sex bias, women accounted for just 29% of the study population. Renewed efforts are urgently needed to ensure inclusive drug trials in urology. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e289 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Andres Guillen Lozoya More articles by this author Candace Granberg More articles by this author Vidit Sharma More articles by this author Patricio Gargollo More articles by this author Kevin Koo More articles by this author Expand All Advertisement PDF downloadLoading ...

An overview of the recent progress in Middle East Respiratory Syndrome Coronavirus (MERS-CoV) drug discovery

ABSTRACT Introduction The Middle East respiratory syndrome coronavirus (MERS-CoV) has remained a public health concern since it first emerged in 2012. Although many potential treatments for MERS-CoV have been developed and tested, none have had complete success in stopping the spread of this deadly disease. MERS-CoV replication comprises attachment, entry, fusion and replication steps. Targeting these events may lead to the creation of medications that effectively treat MERS-CoV infection. Areas covered This review updates the research on the development of inhibitors of MERS-CoV. The main topics are MERS-CoV‒related proteins and host cell proteins that are involved in viral protein activation and infection. Expert opinion Research on discovering drugs that can inhibit MERS-CoV started at a slow pace, and although efforts have steadily increased, clinical trials for new drugs specifically targeting MERS-CoV have not been extensive enough. The explosion in efforts to find new medications for the SARS-CoV-2 virus indirectly enhanced the volume of data on MERS-CoV inhibition by including MERS-CoV in drug assays. The appearance of COVID-19 completely transformed the data available on MERS-CoV inhibition. Despite the fact that new infected cases are constantly being diagnosed, there are currently no approved vaccines for or inhibitors of MERS-CoV.

Acceptance Factors and Psychological Investigation of Clinical Trials in Cancer Patients.

To understand the degree of oncology patients' awareness of drug clinical trials and oncology patients' willingness to participate in drug clinical trials and the factors influencing them. The differences in the relevant variables of patients' willingness to accept clinical trials were analyzed, and a descriptive analysis was done for the measurement data (mean and standard deviation). Pearson's correlation coefficient analysis was used to examine the correlation between willingness and the demographic variables. Stepwise regression analysis was used to explore the influencing factors of patients' willingness to accept clinical trials. There were no statistical differences in age, gender, education level, marital status, place of residence, monthly income, medical payment method, and treatment time (P > 0.05). Patients' willingness to accept drug clinical trials differed in their cognitive degree of clinical drug trials (P = 0.002). Patients' willingness to accept drug clinical trials differed in their experience in clinical trials (P < 0.001). The correlation difference was statistically significant. The willingness to accept drug clinical trials was negatively correlated with treatment time (R = -0.16, P < 0.05) and positively correlated with awareness of clinical trials and whether they had been subjects (R = 0.16 and 0.43, P < 0.05). Multiple regression analysis showed that patients' willingness was directly influenced by age, treatment time, and whether they had been subjects (F = 21.315, P < 0.001). Age, treatment time, and whether they had been subjects were the direct influencing factors of patients' willingness. This study pointed out that hospitals should do a good job in the publicity of clinical trials of new drugs, expand publicity channels, increase publicity efforts, improve the awareness of clinical trials of the masses, and promote the enthusiasm of the masses to participate in clinical trials of drugs.

Neuroinflammation, immune response and α-synuclein pathology: how animal models are helping us to connect dots

ABSTRACT Introduction A key pathological event occurring in Parkinson’s disease (PD) is the transneuronal spreading of alpha-synuclein (α-syn). Other hallmarks of PD include neurodegeneration, glial activation, and immune cell infiltration in susceptible brain regions. Although preclinical models can mimic most of the key characteristics of PD, it is crucial to know the biological bases of individual differences between them when choosing one over another, to ensure proper interpretation of the results and to positively influence the outcome of the experiments. Areas covered This review provides an overview of current preclinical models actively used to study the interplay between α-syn pathology, neuroinflammation and immune response in PD but also to explore new potential preclinical models or emerging therapeutic strategies intended to fulfill the unmet medical needs in this disease. Lastly, this review also considers the current state of the ongoing clinical trials of new drugs designed to target these processes and delay the initiation or progression of the disease. Expert opinion Anti-inflammatory and immunomodulatory agents have been demonstrated to be very promising candidates for reducing disease progression; however, more efforts are needed to reduce the enormous gap between these and dopaminergic drugs, which have dominated the therapeutic market for the last sixty years.

Characteristic analysis of clinical trials for new traditional Chinese medicines in mainland China from 2013 to 2021.

Based on the clinical trials registered on the platform for the registry and publicity of clinical drug trials of the National Medical Products Administration (NMPA), the registration and approval of clinical trials of traditional Chinese medicines (TCMs) in mainland China from 2013 to 2021 were reviewed. Clinical trials of new TCMs published in Chinese were retrieved from the platform for the registry and publicity of clinical drug trials. The number of registered trials and approved trials, status of clinical trials, therapeutic area of clinical trials for the treatment of diseases, type of trial design, sample size, sponsors, and leading clinical trial centers were evaluated. From 2013 to 2021, a total of 965 clinical trials of new drugs applied in TCM were registered on the aforementioned NMPA platform, comprising 117 phase I trials, 586 phase II trials, 174 phase III trials, 40 phase IV trials, and 48 other clinical trials. The treatment fields included the respiratory system, alimentary tract and metabolism, genetic system and reproductive hormones, and cardiovascular system. Among the 760 phase II and phase III trials, 98.9% were randomized, 95.4% were double-blind, and 98.2% were parallel controlled trials, and the proportion of placebo-controlled trials increased year by year from 2013 to 2021. From 2013 to 2021, 123 new TCMs were approved in mainland China. From 2015 to 2021, the number of registered clinical trials of new TCMs remained low. The approval rate was also low, but the clinical trial design was greatly improved.

Contractility assessment of human iPSC-derived cardiomyocytes by using a motion vector system and measuring cell impedance

Predicting drug-induced cardiotoxicity during the non-clinical stage is important to avoid severe consequences in the clinical trials of new drugs. Human iPSC-derived cardiomyocytes (hiPSC-CMs) hold great promise for cardiac safety assessments in drug development. To date, multi-electrode array system (MEA) has been a widely used as a tool for the assessment of proarrhythmic risk with hiPSC-CMs. Recently, new methodologies have been proposed to assess in vitro contractility, such as the force and velocity of cell contraction, using hiPSC-CMs. Herein, we focused on an imaging-based motion vector system (MV) and an electric cell-substrate impedance sensing system (IMP). We compared the output signals of hiPSC-CMs from MV and IMP in detail and observed a clear correlation between the parameters. In addition, we assessed the effects of isoproterenol and verapamil on hiPSC-CM contraction and identified a correlation in the contractile change of parameters obtained with MV and IMP. These results suggest that both assay systems could be used to monitor hiPSC-CM contraction dynamics.

Targeting Mast Cells in Allergic Disease: Current Therapies and Drug Repurposing.

The incidence of allergic disease has grown tremendously in the past three generations. While current treatments are effective for some, there is considerable unmet need. Mast cells are critical effectors of allergic inflammation. Their secreted mediators and the receptors for these mediators have long been the target of allergy therapy. Recent drugs have moved a step earlier in mast cell activation, blocking IgE, IL-4, and IL-13 interactions with their receptors. In this review, we summarize the latest therapies targeting mast cells as well as new drugs in clinical trials. In addition, we offer support for repurposing FDA-approved drugs to target mast cells in new ways. With a multitude of highly selective drugs available for cancer, autoimmunity, and metabolic disorders, drug repurposing offers optimism for the future of allergy therapy.

Clinical Trials of New Drugs for Vascular Cognitive Impairment and Vascular Dementia.

Population aging has challenged the treatment of cognitive impairment or dementia. Vascular dementia is the second leading cause of dementia after Alzheimer’s disease. Cognitive consequences after ischemic brain injury have been recognized as a preferred target for therapeutic strategies, prompting the search for potential agents. The keyword “vascular dementia” was used to search ClinicalTrials.gov to determine agents represented in phases I, II, III, and IV. The agents were classified on the basis of their mechanisms. Of the 17 randomized controlled trials meeting our inclusion criteria, 9 were completed in the past 10 years, and 8 are ongoing or in the planning stages. We also identified one trial in phase I, nine in phase II, six in phase III, and one in phase IV. Fewer trials of new drugs for improving cognition or ameliorating the behavioral and psychological symptoms of dementia target vascular dementia than Alzheimer’s dementia. Drug trials on vascular dementia overlap with drug trials targeting functional outcomes in cerebrovascular disease. International pharmaceutical companies’ investment in new drugs targeting VCI and vascular dementia remains insufficient.

On the use of wearable sensors as mobility biomarkers in the marketing authorization of new drugs: A regulatory perspective.

The loss of mobility is a common trait in multiple health conditions (e.g., Parkinson's disease) and is associated with reduced quality of life. In this context, being able to monitor mobility in the real world, is important. Until recently, the technology was not mature enough for this; but today, miniaturized sensors and novel algorithms promise to monitor mobility accurately and continuously in the real world, also in pathological populations. However, before any such methodology can be employed to support the development and testing of new drugs in clinical trials, they need to be qualified by the competent regulatory agencies (e.g., European Medicines Agency). Nonetheless, to date, only very narrow scoped requests for regulatory qualification were successful. In this work, the Mobilise-D Consortium shares its positive experience with the European regulator, summarizing the two requests for Qualification Advice for the Mobilise-D methodologies submitted in October 2019 and June 2020, as well as the feedback received, which resulted in two Letters of Support publicly available for consultation on the website of the European Medicines Agency. Leveraging on this experience, we hereby propose a refined qualification strategy for the use of digital mobility outcome (DMO) measures as monitoring biomarkers for mobility in drug trials.