Major Pharmaceutical Companies Research Articles

Conflicts of Interest Among Cardiology Clinical Practice Guideline Authors in Japan.

Clinical practice guidelines (CPGs) offer disease management recommendations based on scientific evidence. However, financial conflicts of interest between CPG developers and the pharmaceutical industry could bias these recommendations, potentially affecting patient care. Proper management of these conflicts of interest is particularly crucial for maintaining the integrity of CPGs. The study aimed to evaluate the extent of financial relationships between the pharmaceutical industry and authors of CPGs for cardiovascular diseases in Japan. The study analyzed personal payments from the pharmaceutical industry to authors of cardiovascular disease CPGs published by the Japanese Circulation Society from January 2015 to December 2022. Payment data, including speaking, consultancy, and writing fees from 2016 to 2020, were extracted from a publicly available database containing personal payments disclosed by all major pharmaceutical companies. A total of 929 unique authors from 37 eligible Japanese Circulation Society CPGs were identified. Notably, 94.4% of these authors received personal payments from pharmaceutical companies, totaling >US $70.8 million. The mean±SD payment per author was US $76 314±138 663) and the median payment per author was US $20 792 (interquartile range: US $4262-US $76 998) over the 5-year period. Chairs of CPGs received significantly higher payments than other authors. More than 80% of authors in each CPG received personal payments. The study elucidated that there were considerable financial relationships between pharmaceutical companies and cardiology CPG authors in Japan. This finding deviates from international conflict of interest management policies, suggesting the need for more stringent conflict of interest management strategies by the Japanese Circulation Society to ensure the development of trustworthy and evidence-based CPGs.

Aşı Tereddüdünü Anlamak: Covid-19 Aşısı ile İlgili Komplo Teorilerinin ‘Twitter’ Üzerinden Analizi

The vaccine hesitancy developed during the COVID-19 pandemic has spread the disease, delayed immunity, and increased death rates. Social media platforms have contributed to the spread of doubts, misinformation about vaccines. Twitter, being one of the most popular social networks in Türkiye, has become a significant platform for vaccine polarization. This study aims to examine the reasons for vaccine hesitancy and conspiracy theories developed by Turkish users on Twitter. 3939 tweets were analyzed with the hashtags #aşıyahayır (#notovaccine), #aşıolmayacağım (#Iwillnotgetvaccinated), #denekolmaTürkiye (#donotbeatestsubjectTürkiye), #aşıolmakistemiyorum (#Idonotwanttogetvaccinated). The examined categories are as follows: scientific (the highest number of comments in this category were related to medical side effects), miscellaneous (the highest number of comments were about the lack of mentioning reasons for vaccine hesitancy), conspiracy theories (the highest number of comments were about major pharmaceutical companies), and general content (opinions against administering Covid-19 vaccines to children).

Trends in COVID-19 Vaccine Development: Vaccine Platform, Developer, and Nationality.

Various vaccine platforms, including emerging platforms, have been applied in the development of COVID-19 vaccines. Biotechnology startups often lead the development of new medical technologies, whereas major pharmaceutical companies and public institutions have long contributed to vaccine development. In this study, vaccine platforms and developers involved in COVID-19 vaccine development were analyzed, elucidating the trends of vaccine platforms used, the country distribution of the developers, and differences in the profiles of developers by vaccine platform technologies and country. The analysis revealed that conventional, established, and emerging vaccine platforms have been widely used and that older platforms are more advanced in clinical development. It also demonstrated the emergence of China, in addition to the U.S., while many pharmerging countries have been engaged in development. Startups have significantly contributed to the development of viral vector and RNA-based vaccines, suggesting their important role in the application of novel technologies. The major developers differ by country and region. Alliances, including international collaborations, have progressed in late clinical development. Based on these results, future perspectives of pandemic vaccine development and implications for policy and corporate strategies are discussed.

The major epidemiologic, microbiologic, immunologic, and clinical aspects of Lyme disease that form the basis for a newly developed vaccine that may become available soon for human use.

Working together, two major pharmaceutical companies have developed a Lyme disease vaccine consisting of recombinant-derived outer surface protein A (OspA) of the etiologic agent Borrelia burgdorferi. Multiple clinical trials have shown the vaccine to have good safety and efficacy results, and it is hoped that it would become available for human use at least by the year 2025 after receiving approval from the U.S. Food and Drug Administration. There are still challenges left to ensure that the vaccine has, at most, minimal side effects. Also, because the previously developed Lyme disease vaccine was discontinued in 2002 after four years of distribution, due in part, for frivolous reasons having little or no scientific basis, that even led to legal entanglements involving the vaccine manufacturer and some of the medical personnel overseeing the clinical trials, there will be concerns that this newly developed one could be subject again to some of the same unnecessary scrutiny rendering its implementation suboptimal. Initially this review will focus on the key epidemiological, microbiologic, immunologic and clinical aspects of Lyme disease that provide the foundation for developing this type of vaccine that could have a serious impact on the prevalence of this and even certain other tick-transmitted infections.

Hyperthermia in Combination with Emerging Targeted and Immunotherapies as a New Approach in Cancer Treatment

Despite significant advancements in the development of novel therapies, cancer continues to stand as a prominent global cause of death. In many cases, the cornerstone of standard-of-care therapy consists of chemotherapy (CT), radiotherapy (RT), or a combination of both. Notably, hyperthermia (HT), which has been in clinical use in the last four decades, has proven to enhance the effectiveness of CT and RT, owing to its recognized potency as a sensitizer. Furthermore, HT exerts effects on all steps of the cancer–immunity cycle and exerts a significant impact on key oncogenic pathways. Most recently, there has been a noticeable expansion of cancer research related to treatment options involving immunotherapy (IT) and targeted therapy (TT), a trend also visible in the research and development pipelines of pharmaceutical companies. However, the potential results arising from the combination of these innovative therapeutic approaches with HT remain largely unexplored. Therefore, this review aims to explore the oncology pipelines of major pharmaceutical companies, with the primary objective of identifying the principal targets of forthcoming therapies that have the potential to be advantageous for patients by specifically targeting molecular pathways involved in HT. The ultimate goal of this review is to pave the way for future research initiatives and clinical trials that harness the synergy between emerging IT and TT medications when used in conjunction with HT.

INVESTIGATING THE IMPACT OF PROFITABILITY ON THE STOCK PRICES OF SELECTED PHARMACEUTICAL COMPANIES- PRE AND POST IPA 2005 IMPLEMENTATION

INVESTIGATING THE IMPACT OF PROFITABILITY ON THE STOCK PRICES OF SELECTED PHARMACEUTICAL COMPANIES- PRE AND POST IPA 2005 IMPLEMENTATION

The impact of supply chain integration on operational performance with supply chain capability

Force majeure in Indonesia, especially during pandemics, causes a drastic fluctuation in the market and makes many medicine products related to the pandemic become scarce and stocked out. Major pharmaceutical companies manufactured in Indonesia need solutions for the significant change in demand level and find solutions to balance the supply and demand level. According to the existing literature, by doing internal integration, supplier integration, and customer integration, and supported with supply chain capability, companies can find solutions regarding market fluctuation and increase their competitive performance. This research uses 102 listed Indonesians chosen by the purposive sampling method. Research analysis was conducted using structural equation modeling and SmartPLS 3 software. This research finds that, in general, supply chain capability influences competitive performance. Meanwhile, internal integration by sharing activity information in departments and coordinating integrated planning can positively and significantly affect supplier integration and customer integration. Sharing inventory and information with suppliers and coordinating with suppliers about materials availability significantly influence supply chain capability. Internal integration also has a significant influence on supply chain capability. Customer integration with information sharing with customers and the company involving the customers when demands influence supply chain capability. Supply chain integration (internal, supplier, and customer) does not directly impact operational performance, so supply chain capability is a perfect intervening variable. Supply chain capability can help internal and external integration better affect competitive performance. This research also makes practical contributions to give managers input about how internal integration, supplier and customer integration, and supply chain capability can affect companies' competitive performance.

The Major Hypotheses of Alzheimer's Disease: Related Nanotechnology-Based Approaches for Its Diagnosis and Treatment.

Alzheimer's disease (AD) is a well-known chronic neurodegenerative disorder that leads to the progressive death of brain cells, resulting in memory loss and the loss of other critical body functions. In March 2019, one of the major pharmaceutical companies and its partners announced that currently, there is no drug to cure AD, and all clinical trials of the new ones have been cancelled, leaving many people without hope. However, despite the clear message and startling reality, the research continued. Finally, in the last two years, the Food and Drug Administration (FDA) approved the first-ever medications to treat Alzheimer's, aducanumab and lecanemab. Despite researchers' support of this decision, there are serious concerns about their effectiveness and safety. The validation of aducanumab by the Centers for Medicare and Medicaid Services is still pending, and lecanemab was authorized without considering data from the phase III trials. Furthermore, numerous reports suggest that patients have died when undergoing extended treatment. While there is evidence that aducanumab and lecanemab may provide some relief to those suffering from AD, their impact remains a topic of ongoing research and debate within the medical community. The fact is that even though there are considerable efforts regarding pharmacological treatment, no definitive cure for AD has been found yet. Nevertheless, it is strongly believed that modern nanotechnology holds promising solutions and effective clinical strategies for the development of diagnostic tools and treatments for AD. This review summarizes the major hallmarks of AD, its etiological mechanisms, and challenges. It explores existing diagnostic and therapeutic methods and the potential of nanotechnology-based approaches for recognizing and monitoring patients at risk of irreversible neuronal degeneration. Overall, it provides a broad overview for those interested in the evolving areas of clinical neuroscience, AD, and related nanotechnology. With further research and development, nanotechnology-based approaches may offer new solutions and hope for millions of people affected by this devastating disease.

BIOAVAILABILITY ENHANCEMENT STRATEGIES FOR RIVAROXABAN: A NOTEWORTHY REVIEW

This review article discusses Rivaroxaban (RXB), an anticoagulant that has gained much attention due to its ability to prevent blood clots from forming in the body. However, one of the major challenges pharmaceutical companies face is the low water solubility of RXB, which can lead to difficulties in formulating the drug for oral administration and affect the drug's bioavailability. However, to the best of our knowledge, limited studies have explored enhancing the bioavailability of the RXB. Most of these studies have been purely academic and impractical for industrial use. Therefore, this review article aims to discuss successful studies that have increased the bioavailability of RXB. The goal is to inspire researchers to develop this new drug further. The article covers seven strategies for enhancing the bioavailability of RXB, including microspheres, liposomes, self-nano emulsifying drug delivery system, solid lipid nanoparticles, cocrystals, sustained release, and solid dispersion. The studies discussed in this review offer valuable insights into developing novel drug delivery systems that can help overcome the limitations of existing drugs.

Clinical Application and Synthesis Methods of Deuterated Drugs.

Many drugs have adverse absorption, distribution, metabolism, and excretory (ADME) properties that prevent their widespread use or limit their use in some indications. In addition to preparation techniques and prodrug strategies, deuterium modification is a viable method for improving ADME properties. Deuterated drugs have attracted increasing attention from the pharmaceutical industry in recent years. To date, two deuterated drugs have been approved by the FDA. In 2017, austedo was approved by the FDA as a new drug for Huntington's disease in the United States, the first deuterium drug to be marketed worldwide. Recently (June 9, 2021), donafinil has been listed in China; this result has caused major pharmaceutical companies and the pharmaceutical industry to pay attention to deuterium technology again. In addition, BMS-986165, RT001, ALK-001, HC-1119, AVP-786 and other drugs are in phase III clinical studies, and some solid deuterium compounds have entered phase I and II clinical trials. The deuterium strategy has been widely used in pharmaceutical research and has become a hot spot in pharmaceutical research in recent years. In this paper, the research and development of deuterated drugs are reviewed, and the influence of deuterium modification on drugs, the advantages of deuterium strategies and the synthesis strategies of deuterated drugs are mainly introduced. Hoping to provide references for clinical application, the discovery of new deuterium chemical entities and research and development of new deuterated drugs.

Rheumatology tolerance for cure (RTCure) – an IMI project aimed at prevention and cure of RA

The RT Cure project, supported from the Innovative Medicines Initiative (IMI) has been active for 6 years and involved several European and one Australian rheumatology institutions, six major pharma companies and a few small companies. The present report describes the major aims and results of the project which includenew understanding of specificity and regulation a of adaptive immunity that precedes RA and is active in established disease.use this understanding to predict risk for RA and establish registers of at risk for RA cohorts.support for clinical trials aimed at prevention of RA with knowledge and tools for immune surveillance.The progress in these areas, including the support to successful clinical trials for prevention will provide a basis for further development of prevention of RA using increasingly specific immunotherapies.

Managing the supply chain disruption of essential commodities supply in health care systems during emergency Lagos state, Nigeria

2019 birthed the Coronavirus endemic in China and in 2020, it became an established pandemic across the world. While supply chain analysts had predicted a disruption to the flow of commodities across all sectors, curiosity and concern led us to study the effect of disruptions such as Covid-19 on the supply chain of essential commodities in Africa precisely Lagos, Nigeria. The two types of data sources utilized were; the primary source and secondary sources of data. The data collected was collated and analysed using 2016 Microsoft excel sheet and Statistical Products and Services Solution (SPSS 25.0.0.0) for data analysis. The interview with pharmaceuticals company representative, suggested hiccups in the distribution of vaccines by a major pharmaceutical company to their respective customers. The Covid-19 situation and the necessary lockdown in Lagos state caused a slight disruption in the availability and distribution of essential commodities across the state, the major issues were the lack of a means of accessing transportation to health care facilities and the increment in the price of medicines. While most pharmaceuticals and health service delivery points were not prepared to curb the impact of the emergency situation. In this regard, pharmaceutical companies should ensure flexibility in supply chain by creating supply chain emergency plans, the government should look into establishing a drug bank for essential commodities in the state, while last mile service deliveries should employ the use of telemedicine and patient home delivery services.

Progress in circRNA-Targeted Therapy in Experimental Parkinson's Disease.

Circular RNAs (circRNAs) are single-stranded RNA molecules often circularized by backsplicing. Growing evidence implicates circRNAs in the underlying mechanisms of various diseases, such as Alzheimer's and Parkinson's disease (PD)-the first and second most prevalent neurodegenerative disorders. In this sense, circSNCA, circHIPK2, circHIPK3, and circSLC8A1 are circRNAs that have been related to the neurodegenerative process of PD. Gain-of-function and loss-of-function studies on circRNAs have shed light on their roles in the pathobiology of various diseases. Gain-of-function approaches typically employ viral or non-viral vectors that hyperexpress RNA sequences capable of circularizing to form the specific circRNA under investigation. In contrast, loss-of-function studies utilize CRISPR/Cas systems, antisense oligonucleotides (ASOs), or RNAi techniques to knock down the target circRNA. The role of aberrantly expressed circRNAs in brain pathology has raised a critical question: could circRNAs serve as viable targets for neuroprotective treatments? Translating any oligonucleotide-based therapy, including those targeting circRNAs, involves developing adequate brain delivery systems, minimizing off-target effects, and addressing the high costs of treatment. Nonetheless, RNAi-based FDA-approved drugs have entered the market, and circRNAs have attracted significant attention and investment from major pharmaceutical companies. Spanning from bench to bedside, circRNAs present a vast opportunity in biotechnology for oligonucleotide-based therapies designed to slow or even halt the progression of neurodegenerative diseases.

Central Nervous System Targeted Protein Degraders.

Diseases of the central nervous system, which once occupied a large component of the pharmaceutical industry research and development portfolio, have for many years played a smaller part in major pharma pipelines-primarily due to the well cited challenges in target validation, valid translational models, and clinical trial design. Unfortunately, this decline in research and development interest has occurred in tandem with an increase in the medical need-in part driven by the success in treating other chronic diseases, which then results in a greater overall longevity along with a higher prevalence of diseases associated with ageing. The lead modality for drug agents targeting the brain remains the traditionally small molecule, despite potential in gene-based therapies and antibodies, particularly in the hugely anticipated anti-amyloid field, clearly driven by the additional challenge of effective distribution to the relevant brain compartments. However, in recognition of the growing disease burden, advanced therapies are being developed in tandem with improved delivery options. Hence, methodologies which were initially restricted to systemic indications are now being actively explored for a range of CNS diseases-an important class of which include the protein degradation technologies.

Global adoption of remote technologies to enable patient-centric oncology clinical trials: Analysis by the Bloomberg New Economy International Cancer Coalition.

1584 Background: Fewer than 5% of patients with cancer enroll in a clinical trial, partly due to the significant financial and logistical burden on patients, especially among underserved populations. The COVID-19 pandemic marked a significant shift in the adoption of remote technologies and decentralized trial operations by major pharmaceutical companies. We sought to determine the current global state of adoption of these technologies, understand factors that are driving or preventing adoption of them, and highlight aspirations and direction for industry to enable more patient-centric trials. Methods: The multi-stakeholder Bloomberg New Economy International Cancer Coalition composed of patient advocacy, industry, government regulators, and academic medical centers developed a survey directed to global biopharmaceutical companies of the Coalition with a focus on registrational clinical trials. The survey was organized into three main sections: 1) Impact of different remote monitoring and data collection technologies on patient-centricity; 2) Adoption of these technologies in oncology and all therapeutic areas; 3) Barriers/facilitators to adoption. Results: Administered from October 1 to December 31, 2022, a total of 8 companies completed the survey (response rate: 100%), representing 33% of oncology market by revenues in 2021. Across nearly all remote monitoring and data collection technologies, adoption in oncology trials lags that of all trials. In the current state, eDiary/eCOA is the most utilized technology with 56% and 51% adoption for all trials and oncology trials, respectively, whereas visits in local physician networks is the least adopted at 12% and 7%, respectively. Looking forward, the difference between the current and aspired adoption rate in 5 years for oncology is large, with respondents expecting a 40% or greater absolute adoption increase in 8 out of the 11 technologies (Table). Furthermore, respondents identified digitally enabled recruitment, local or mobile imaging capabilities, and local physician networks as those technologies that would be most impactful for improving patient centricity in the long term. Conclusions: This survey is the first by a coalition of global stakeholders to determine the current state and future aspirations for the use of remote technologies in oncology clinical trials. These efforts may galvanize momentum towards greater adoption of enabling technologies supporting a new paradigm of trials that are more accessible, less burdensome, and more inclusive.[Table: see text]

RWD185 The Return on Investment of Real World Evidence

The RWE Leadership Forum (RWLF) is a group of senior RWE executives across major pharma companies, with the objective to understand and respond to RWE challenges and opportunities with a single expert voice, with the aim of improving outcomes, business efficiencies and return on investment. The RWLF propose a common framework for discussing the value and impact of RWE for companies, quantifying benefits and risks of conducting RWE studies in order to support leadership prioritise investment decisions.

A comprehensive review of phytochemical components as potential antidepressants

Depression is a heterogeneous mood disorder that has been classified and treated in a variety of ways. Despite the fact that a variety of synthetic medications are utilized as conventional treatment for clinically depressed patients, these drugs have side effects that can jeopardize the therapeutic outcome. In recent decades, there has been a rise in research and interest in the psychopharmacology of natural treatments. Thus, it’s worthwhile researching for antidepressants derived from plants that have a demonstrated effect and a favorable benefit-to-risk ratio. By virtue of their medicinal constituents, a variety of medicinal plants and medicines produced from these plants have exhibited antidepressant properties. As a result, major pharmaceutical companies are currently researching plant materials extensively for their possible medical benefit. Depression is caused by low levels of monoamines such as noradrenaline, dopamine, and serotonin in the brain. Therefore, treatments that restore lowered levels of these monoamines in the brain by blocking monoamine oxidase or decreasing reuptake of these neurotransmitters could be beneficial in the treatment of depression. The current review focuses on medicinal plants and plant-based formulations that have been shown to have antidepressant effect in both animal and human studies.

Abstract 4563: Measuring immunotherapy responses ex vivo using novel 3D culture platform: E-slice

Abstract Immunotherapies have provided dramatic and life-saving results in some patients; however, their effectiveness varies greatly in different tumors, even among patients with the same clinical diagnosis. Clearly, a better system to evaluate the personalized response to immunotherapies will greatly benefit the patients and reduce the cost of care. In addition, due to their theoretical and demonstrated benefits in providing durable responses, new immunotherapies are avidly sought after by most major pharmaceutical companies, numerous biotech companies, and academic laboratories. However, preclinical evaluation of new immunotherapy efficacy is challenging and inaccurate using most experimental model systems.E-slice is a faithful model of an individual cancer patient’s tumor. It is a proprietary 3D tissue slice culture platform, and E-slices are generated by making thin sections of intact, fresh tumor tissues from patients. As such, immune components and the TME in E-slices are native to each patient’s tumor. E-slice overcomes many of the limitations of other experimental systems for multiple reasons. The E-slice platform: 1) uses chemically defined, serum-free medium; 2) measures viability changes upon treatment longitudinally, from the same tissue, which allows both absolute and relative responses for as short as 4 days or as long as over 4 weeks ex vivo; 3) can be generated from any solid tumor tested thus far (breast, lung, colorectal, pancreas, brain, head 7 neck, and others) from patient tumors directly or from PDX and genetically engineered mouse models; 4) retains the native TME and tissue architecture because E-slices are never dissociated or otherwise reconstituted; 5) is compatible with biopsies as well as surgical samples; 6) has been shown to accurately predict individual patient treatment responses to chemotherapies and targeted therapies in 4-12 days, paving the way for evidence-based personalized treatment selections in a clinically actionable time frame.Specifically for immunotherapy response measurements, key differentiators of the E-slice platform from other ex vivo systems for immunotherapy responses are: 1) E-slice is generated from fresh patient tumor tissues with tumor-trained and resident immune cells and not artificially introduced PBMCs used in most other systems; 2) serum-free, chemically defined medium and does not artificially activate or suppress the immune system; 3) E-slice has been validated by single-cell RNA-sequencing to maintain immune cells in their native state up to 8 days ex vivo; 4) E-slices can be used to detect secreted protein and metabolic biomarkers in the conditioned media pre- and post-treatment; 5) E-slice can measure immunotherapy responses ex vivo in 8 days. In summary, we present a novel ex vivo 3D human tumor tissue drug sensitivity platform that can enhance immunotherapy development pipelines and clinical deployment. Citation Format: Thomas D. Gallup, Jose A. Maldonado, Corina Margain, Min P. Kim, David F. Gallup, Kyuson Yun. Measuring immunotherapy responses ex vivo using novel 3D culture platform: E-slice. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4563.

Cross-sectional analysis of pharmaceutical payments to Japanese board-certified gastroenterologists between 2016 and 2019

ObjectivesLimited evidence is available regarding the financial relationships between gastroenterologists and pharmaceutical companies in Japan. This study analysed the magnitude, prevalence and trends of personal payments made by major pharmaceutical...

Clinical Trials: National and International Perspective

Due to its expense and unpredictability, outsourcing has gained widespread acceptance in the pharmaceutical industry for the development and global trials of novel medications. Due to its sizable treatment-naive population, human resources, technical skills, adoption/amendment/implementation of rules/laws by regulatory bodies, and shifting economic environment, India would be the most sought-after country for contract pharma research and development. Nonetheless, there are still "miles to go" to meet the requirements to guarantee India's success. India is ambitious and optimistic about luring major pharmaceutical companies to conduct their clinical trials there despite all the obstacles.