Phase I cGMP Drug Manufacture at the CRU: 3 BIG Benefits

The regulatory environment continues to move toward requiring drug manufacturing at current good manufacturing practice (cGMP)-compliant pharmacies. This trend and other factors make it increasingly attractive to use cGMP compounding on-site at your CRU for early development. Let’s look at Three Big Benefits for Phase I drug manufacturing:

Preclinical Success to Clinical Failure: Do We Have a Model Problem or an Endpoint Problem?

As the AACR (American Association for Cancer Research) Annual Meeting is fast approaching, many industry and academic scientists are busy preparing talks and posters for what they hope will be the next new wave in cancer therapy or the next “new and improved” preclinical model. However, while these may be long shots, it’s the scientific drive for improvement that keeps us moving forward. As, patients and clinicians, we are desperately looking for new therapies, even if the odds are against us. The desire to fulfill that unmet medical need is exactly how the one new drug is discovered. New oncology drugs only have a 5% success rate once making it from Phase I clinical trials to FDA approval. This is the lowest success rate among the 21 major disease indications.1

The Biosimilars Landscape: What All Developers Need to Know

As biosimilars to treat rheumatic diseases begin get approval from the FDA, biosimilar development remains a hot topic in drug development. Sponsors estimate a 35% growth of biosimilars in their development pipelines by 2020, but face a wide variety of regional and global markets along with shifting guidelines and recommendations, stressing the need to understand this rapidly changing landscape. What is the real potential for clinical and health-economic benefits offered by these agents?

Finding the Other 90%: Attracting Naïve Patients to RA Studies

A recent study by Tufts Center for the Study of Drug Development, based on a survey of 2,000 physicians and nurses primarily in the United States and Europe, found that 91% of physicians feel ‘somewhat’ or ‘very’ comfortable discussing the opportunity to participate in a clinical trial with patients, but actually refer less than 0.2% of their patients into clinical trials.1 In conjunction, more than 80% of patients say they are willing to participate in clinical research studies, but only around 10% actually do so.2 It is further reported that while 85% of patients are generally comfortable presenting any clinical research information they find to their doctor, only 17% have actually done so.3 And what of those patients that are interested in participating in a clinical study only to find they are ineligible? When queried on next steps after finding out he/she did not qualify, 36% stopped looking for a clinical research study to participate in.3 This latter fact is a staggering waste of potential when you consider that there are currently >130 planned or ongoing industry-sponsored Phase II-III rheumatoid arthritis (RA) studies to choose from (>210 when you consider any type of study sponsor).4

Phospho-Flow Cytometry for the Screening of Intracellular Signaling Events in Cancer Cells and Immune Cells

Pre-clinical research on the development of small molecule inhibitors that block the activity of disease-associated kinases continues to be a major focus of cancer therapy. Therefore, robust platforms that can quantify the phosphorylation state of these kinases are valuable to drug development efforts. Using the MV-4-11 acute myeloid leukemia (AML) model, this update describes new in vitro and ex vivo phospho-flow services that measure phospho-kinase signaling with consistency and reproducibility. This platform uses fluorescence-labeled antibodies that recognize proteins only when phosphorylated on specific amino acid residues that regulate their function. Furthermore, we demonstrate how phospho-flow can integrate high throughput immunophenotyping with phospho-protein detection, which provides an advantage over ELISA-based and other conventional techniques.

The State of Modeling Preclinical Immuno-Oncology Pharmacology

The field of cancer immunology or immuno-oncology (I/O) dates back to the 1890’s with efforts by William Coley to treat malignancies by infection with certain bacterial strains.1 Fast forward 120 years, and we have observed the clinical success of multiple checkpoint inhibitor antibodies against cancer specific T cell negative regulatory pathways in multiple cancer types.2 Because of these clinical successes with antibodies targeting CTLA-4, PD-1, and PD-L1 (e.g., ipilimumab, nivolumab, pembrolizumab, atezolizumab, avelumab), vast resources in biotech and large pharma are being directed toward preclinical I/O research in an effort to develop novel immunotherapies.

A Practical Business Approach to Data Management for Clinical Trial Efficiency

Today’s clinical trials have become more complex and expensive, pressuring pharmaceutical companies to further improve their clinical trial operations. Clinical trial data management is one area where both sponsors and contract research organizations (CROs) can uncover new efficiencies, increase cost-saving measures and better meet diverse operational reporting needs across the clinical development cycle.

Pop Quiz: What’s Your Patient Centricity IQ?

What issues do patients cite as barriers to clinical study participation? How far are they willing to travel to participate in a study and how much more willing are they to participate knowing that their physician is aware of the study?

An Introduction to Immunohistochemistry

Immunohistochemistry (IHC) is an assay that utilizes the biological collaboration of Histology and Immunology. The biochemical interactions between an antibody and antigen permit visual distribution and localization of antibody–antigen interactions. This allows morphology, antigen intensity, and spatial relationships to be determined.

TDAR Assays for In Vivo Assessment and Testing

The immune system is the body’s main defense against foreign materials and biologic agents such as bacteria, viruses, chemicals, and foreign cells and tissues. The immune response includes specific action of lymphocytes (one type of white blood cell) and is facilitated by other white blood cells, including neutrophils, monocytes, macrophages, eosinophils and basophils. The immune system can be viewed as a system controlled by negative feedback, meaning that normally it must reduce the effects of disturbance or invaders through self-regulation.