The Role of the CRO in Frontloading Cardiovascular Safety

The Role of the CRO in Frontloading Cardiovascular SafetyCardiovascular safety remains a leading cause of drug attrition during preclinical and clinical development, accounting for discontinuation of approximately one third of marketed drugs.

These liabilities, which pertain to both cardiovascular- and non-cardiovascular-targeted drugs, can be identified during early development by addressing cardiovascular safety endpoints prior to the selection of a drug candidate, a process known as ‘frontloading’. Although not mandated by the key regulatory guidance for safety pharmacology (ICH S7A; US FDA, 2001), an increasing number of companies choose to conduct early non-GLP cardiovascular safety studies in support of decisions on the progression of their compounds. Continue reading

Biomarker Development for Parkinson’s Disease

Biomarker Development for Parkinson’s Disease

Parkinson’s Disease (PD) is a chronic neurodegenerative disease with no known cure, no certain cause, and no clinically available test for simple diagnosis. Research advances have been made, but there still remains a huge unmet need for diagnostic and disease progression biomarkers.

Research on this disease is focused on the changes that occur in the brain. Research has shown that the nerve cells in the brains of Parkinson’s patients have abnormal protein deposits that may disrupt normal brain function and cause Parkinsonian symptoms, such as tremor, slowness of movement, and rigidity, among others. Continue reading

Accelerating Candidate Selection: Solutions for Lead Optimization Pharmacology & Toxicology

Lead optimization (LO) is one of the most expensive and time-consuming stages of the drug development process due to the number of programs running simultaneously and the number of molecules within each of those programs. Covance’s Lead Optimization Pharmacology & Toxicology services are designed to help you select the best molecule for candidate selection and further development. Our ability to integrate service lines, such as pharmacology, biomarkers, imaging and safety, and thoughtfully add endpoints to studies, maximizes the number of questions being answered in each study leading to improved probability of technical success. The following video gives an overview of our Lead Optimization Pharmacology & Toxicology services and the benefits of choosing Covance as your LO partner.

Using Next-Generation Sequencing to Detect Epigenetic Alterations – The Impact on Clinical Oncology

Using Next Generation Sequencing to Detect Epigenetic Alterations - The Impact on Clinical Oncology

How can identical twins, with the same genetic makeup, experience different diseases? Scientists believe this is due to epigenetic marks or chemical tags that play a role in controlling the activities of genes. The study of the epigenetic landscape has already generated recent breakthroughs in the detection, treatment and prognosis of many diseases, including cancer.

These breakthroughs are due in part to large-scale mapping efforts of cancer genomes coupled with the rapidly dropping costs of high-throughput next-generation sequencing technologies. Identification of mutations and epigenetic analysis are the next frontier for finding reliable biomarkers and developing targeted therapies.

Next-generation sequencing platforms are particularly powerful for mutational and epigenetic studies due to their ability to quickly analyze the entire genome through multiple methods of sequencing, such as DNA, RNA, miRNA, whole genome, exome, targeted, ChIP-Seq, methylome and epigenome. As a result, researchers obtain comprehensive, clinically relevant data sets.

With these resulting data, computational biologists can mine both open source data sets along with data sets from clinical trials to narrow down options for prospective biomarkers. Continue reading

Obtaining Early Insights Into Safety and Efficacy: The Benefits of Preclinical In Vivo Imaging

The benefits of preclinical in vivo imagingFirst established as a standard practice in clinics, in vivo imaging also benefits translational or preclinical research. For the past 25 years, many studies have relied on in vivo imaging as a method to quantify treatment response and gain early insights on efficacy. Now, as the technology advances, researchers can expect to benefit from greater spatial resolution and software advancements that allow faster, cost-effective translation of study results.

“Imaging often gives you unique information that can’t be obtained any other way.  The phenomena that you would observe preclinically may be the same disease state in the clinical trial,” says Michael Cockman, Senior Scientist and Manager of the Imaging Center at Covance. “It’s common to hear from a client who wants to test a type of imaging, called a modality, in a particular disease state to find out if it is appropriate for clinical development later.” Continue reading

Novel Tissue Types for the Development of Genomic Biomarkers

Novel Tissue Types for the Development of Genomic BiomarkersImagine a simple clinical test that can not only diagnose a disease, but that can also identify the exact, personal therapeutic regime to cure it. Not only that, imagine tests that can accurately predict the potential of developing a disease and provide an individualized roadmap on how it will progress. Now imagine that all you had to do was spit in a vial, or have a few hairs plucked for the analysis. While the promise of “personalized medicine” is technologically a reality, it relies on the development of disease and progression biomarkers. Continue reading

Managing Drug Development Challenges for Inflammation Therapies

InflammationIncorporating technologies such as biomarkers into the development of inflammation therapies can improve the development and delivery of the right therapy, at the right dose, to the right patient. Nonetheless, there are numerous risk factors inherent in inflammation studies and drug development overall. It’s crucial to identify these risks early on in your development plan and develop mitigation strategies that will help decrease your chances for failure. Continue reading

Enrichment Strategies for Phase I Oncology Clinical Trials

Oncology Clinical TrialsStudy efficiency is critical in the competitive Phase I oncology environment where a large number of (NMEs) are all competing for the same medical resources.

There is a growing trend to evaluate predictive biomarkers in enriched patient populations in early phases of clinical trial. Novel biomarker-driven, adaptive clinical trial designs can facilitate rapid evaluation of drugs, help validate multiple predictive biomarkers, minimize exposure of patients to ineffective therapies, and potentially allow accelerated drug approval in molecularly defined populations. Continue reading