The FDA released a Draft Guidance in December (2018) on the evidentiary framework and standards required to achieve qualified biomarkers. It is intended to cover a regulatory gap related to the use of biomarkers outside of specific drug programs. As such, this Draft Guidance supports the Qualification of Drug Development Tools section (507) of the 21st Century Cures Act enacted on December 13, 2016 and provides the framework for developing the data set (evidence) supporting designation of a biomarker as qualified for a particular context of use (COU). Within this context of use, the qualified biomarker, “…can be relied on to have a specific interpretation and application in drug development and regulatory review…” While biomarkers measured by medical devices are outside the scope of the Draft Guidance, the Agency broadens the practical scope beyond qualified biomarkers to include the evidence needed to support the use of biomarkers in INDs, NDAs and BLAs:
“Many principles discussed in this guidance could also be appropriate when considering the evidence scientifically sufficient to support the use of a biomarker in an individual drug development program (e.g., investigational new drug application, new drug application, or biologics license application submissions).” Continue reading
Pharmaceutical companies are increasingly relying on biomarkers to deliver precision medicine in immuno-oncology. Biomarkers can accelerate drug development and reduce the overall cost; they also allow sponsors to identify failed treatments sooner so that resources are not wasted on expensive, late-stage trials with unsafe or inactive compounds. Finally, these tests lead to better outcomes for patients, which help companies make a stronger case for reimbursement.
However, biomarker discovery requires substantial time and resources. While expenses will likely be outweighed by increased development efficiency, companies must ensure that drug and diagnostic timelines are closely aligned so that the treatment and test can launch simultaneously. Technical, workflow and commercial factors are critical to the successful use of immuno-oncology biomarkers. Continue reading
Kidney disease is often called a “silent killer” as it often develops unrecognized and
gradually progresses into chronic kidney disease. Earlier detection to identify kidney disease and slow its progression has relied on measuring changes in two key biomarkers – glomerular filtration rate (GFR) and albuminuria.
Dr. Barbara Gillespie, vice president and therapeutic head of nephrology at Covance, was recently asked to attend an invite-only workshop on March 15-16, 2018 sponsored by the National Kidney Foundation (NFK), U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).
As the only representative from a CRO invited to this unique meeting, Dr. Gillespie will offer valuable insights from the perspective of clinical research. She also serves on the NFK regional medical advisory board and is the only CRO member of the NFK scientific advisory board for chronic kidney disease (CKD) registry.
The rise of immunotherapy has been meteoric — there are now well more than 1,000 immuno-oncology (IO) trials ongoing according to clinicaltrials.gov. Finding and enrolling the appropriate patients for these potentially revolutionary treatments has presented a profound challenge, one that was recently covered in the aptly titled New York Times article: A Cancer Conundrum: Too Many Drug Trials, Too Few Patients. Another piece of the puzzle is clinical trial design, which can be especially elaborate when testing combination treatments in IO. Exacerbating these issues, IO trials are an increasingly competitive race to market. There is great value assigned to reducing development times and being the first drug approved within a class or for a specific indication.
This blog article discusses the current state of immuno-oncology studies, strategies for enhancing patient recruitment, the role of companion diagnostics and solutions for dealing with the complexity of IO combination studies. Continue reading
The majority of today’s approved companion (and complementary) diagnostics (CDx) support personalized medicine efforts in oncology, a testament to researchers’ growing knowledge regarding the genetic pathways impacted in various cancers. That understanding increases our ability to convert such knowledge of biology into treatments that specifically target disease based on a tumor’s genetic makeup. This has led to significantly improved outcomes for many patients.
But can we leverage the knowledge of the biology of other disease states along with the appropriate technical progress into successful CDx expansion beyond oncology? Given that nearly 50% of all compounds in clinical development are dropped for lack of efficacy, CDx may represent a viable approach to improve this statistic and boost the efficiency of drug development efforts. Promising clinical areas where CDx may play an important role include immunology, rare and orphan diseases, and neurodegenerative diseases such as Alzheimer’s disease. Continue reading
Identification of new medicines for kidney disease remains an ongoing challenge in drug development. This challenge includes establishing new biochemical measurements (biomarkers) which can sensitively and accurately reflect the status of renal health and any associated changes in renal function. Sponsors are exploring many options to improve the application of biomarkers in preclinical use in order to better inform early phase safety studies and downstream clinical trials.
Katherine Landschulz, PhD, associate director of the translational biomarker solutions laboratory, and veterinarian pathologist Laura Boone, DVM, PhD, recently shared their experiences working on renal disease studies at Covance. They discussed their insights on how biomarkers are being used in preclinical studies to predict safety and advance translational medicine in drug development.
Of the 422 million people in the world with type 1 and 2 diabetes, 20-30% will develop diabetic nephropathy, also called diabetic kidney disease (DKD) – the leading cause of renal failure in the western world1.
From the perspective of drug developers, testing new therapies to prevent, treat or reverse this serious complication relies on biomarkers for timely and accurate patient identification and efficacy or safety monitoring.
Jennifer Ennis, MD, medical director at LabCorp and D. Walt Chandler, PhD, executive director at LabCorp, recently shared their thoughts on today’s biomarkers to detect and monitor DKD.
Over the past several years, the scientific community has made tremendous progress in advancing our understanding of the immune system, from the basic functions of its various components to molecular pathways that operate within those components. With new, state-of-the-art tools and technologies, immunologists now have the ability to better understand the mechanisms of immune response to various antigens, thereby aiding them in the development of novel approaches to treat immune-system-related diseases and better design vaccines to combat infectious agents and cancer.
Currently, one of the most sensitive techniques available for the detection, measurement, and functional analysis of immune cells is the enzyme-linked immunospot (ELISPOT) assay. Covance uses the ELISPOT technique in applications such as evaluation of vaccine efficacy and immunogenicity of biological products.
The NIH defines precision medicine as “an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person1.” In cancer patients, we can rephrase the definition to “through detailed understanding of a cancer’s biology, providing the right drug, for the right patient, at the right time.”
In order to identify the correct drug, biomarkers are used to identify patients that can be treated with the appropriate therapy for their cancer. The FDA defines biomarkers as “a defined characteristic that is measured as an indicator of normal biological processes, pathogenic processes, or responses to an exposure or intervention, including therapeutic interventions2.” Great strides have been made in the discovery and validation of biomarkers in drug development. Continue reading
The complexity of clinical trials continues to rise. New biomarkers for safety and efficacy continue to emerge, and new types of information – such as genomic profiles – have become critical to submissions for drug approval. Against this dynamic backdrop the central challenge facing trial sponsors remains the same: the need to bring together diverse data sets, draw meaningful insights from them and act quickly to maximize return on investment.
Covance and Global Specimen Solutions, Inc. (GSS) have announced a five-year strategic alliance that gives Covance clients access to a comprehensive and integrated solution that includes GlobalCODE®, snapTRACKTM and GSS wraparound services. This will enable near real-time data cleaning across clinical trial data sources which allow interventions to be made during the clinical trial, impacting overall trial execution and data validity. This also allows cross-protocol, cross-program analytics which provide context for data results, assuring robust clinical trial design and operational excellence. Continue reading