Balancing the need for early access to treatments for rare disorders and protecting patients’ safety and the viability of promising novel treatments
Over the past 10 years, I have been asked to provide advice on whether or not to provide open-label, long-term treatment with novel drugs during early development. I had followed the orthodoxy to not offer such treatment until some demonstration of beneficial effect and robust preclinical safety data are generated. However, our understanding of acceptable risk in the context of diseases with high unmet medical need is changing. I recently was involved in such a case in which an open-label extension for a phase 1b study seems to make sense.
Examples of patients’ growing influence are the Patient Focused Drug Development Initiative (PFDDI), created out of the Food and Drug Administration Safety and Innovation Act (FDASIA), which is directed to incorporate patient view point in the regulatory process. Several of the PFDDI 2014 meetings are relevant to my area of expertise, neuroscience: Fibromyalgia (March 26, 2014); Neurological manifestations of inborn errors of metabolism (June 10, 2014); Parkinson’s disease and Huntington’s disease (TBD). Another example is the collaboration between the FDA and the Duchenne Muscular Dystrophy patient community to advance useful regulatory tools for benefit-risk consideration in DMD (page 58). Similar efforts to incorporate patient input for orphan disease are underway in Canada. Formalizing consideration of patients’ preferences will likely have direct implications for determining acceptable risk when benefit is largely unknown and even the regulatory value of the data provided by open-label extension studies.
This shift has significant implications for biotech and pharmaceutical companies in various areas, such as ethical (eg, exposing patients to long-term risks with no extenuating benefit), legal (eg, liability for negative outcomes) and financial (higher drug production costs, implementation of longer trials). For those of us in clinical development there are also a number of significant implications, such as larger placebo effects because of higher expectations about treatment success, a decrease in the number of eligible patients, and conflicts with patients who want to continue on the drug even after blinded trials show no efficacy and development has been discontinued.
So what implications does this change in thinking have for future drug development? It means that compounds and patient populations appropriate for potential early open-label extensions need to do a lot more upfront planning and implementing. For instance:
- Early engagement with the patient community
- Fortification of natural history data
- Acceleration of preclinical safety studies
- Early vetting with Regulatory agencies
- Robust inform consent development with external input
- Development of a solid long-term plan for data interpretation to provide the reassurance needed to acquire adequate financial support.
To share your views on open-label extension studies and discuss the risks and benefits of an open-label extension study for your disease indication of interest, please contact us.
Communications During Drug Development
Helping physicians and patients get access to new drugs and medical devices requires more than showing that a product works. In this article, we focus on the hurdles that the biopharmaceutical industry faces. Similar challenges face the medical device industry; however, as they say, the devil is in the details.
Typically, the first hurdles facing the biopharmaceutical industry are demonstrating that the product is safe and effective and that it can be consistently and reliably manufactured. However, a successful product launch also requires surmounting the hurdles of reimbursement and commercialization. Continue reading
Over the past several years, the life science community has gained an improved understanding of the immune system–from B and T cells to molecular pathways. With new, state-of-the-art tools and technologies, immunologists now have the ability to take a holistic approach to understanding the mechanisms of immune response. These applications help us devise methods to treat immune system-related diseases and to design better 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’s Translational Biomarker Solutions group uses the ELISPOT technique to evaluate test subject responses to our sponsors’ vaccines, drugs, and biological products. ELISPOT is also useful in the pre-clinical space, where Covance can assess the toxicity of investigational compounds and biologics, and evaluate the efficacy of vaccines. Continue reading
As the pace of companion diagnostic innovation continues to accelerate, the drug development industry faces several headwinds. Numerous patent ‘cliffs’ are affecting the sales of blockbuster drugs; competition is increasing for a limited clinical trial population in increasingly global trials; and health outcomes pressures from patients, payers and healthcare providers are transforming the drug development process.
Over the past 10 years, advances in analytical technologies have provided new tools to identify patients who are more likely to positively respond to a certain drug or, conversely, experience a negative reaction to the particular therapy. These tools, known as companion diagnostics, are laboratory tests for biomarkers that, once commercialized, are designed to be an accompaniment to the safe and effective use of a particular therapy. Continue reading
When developing a biologic, great science does not always translate into a great product. Doing the rights studies, the right way, is paramount to realizing the product’s potential. Knowing which studies to conduct, when to conduct them and interpreting the data in the context of the product’s development, can make the difference between success and failure.
For Biologics, “The Product is the Process”
Biological medicines, including therapeutic proteins, DNA vaccines, monoclonal antibodies, and fusion proteins are large, complex molecules that cannot be fully defined by physicochemical analytical methods. They are manufactured from genetically modified living cells using processes that are usually complex. Biological medicines are often 200 to 1,000 times the size of small molecule drugs, and because of the biological nature of the starting materials, the manufacturing processes have inherent variability and product heterogeneity. Continue reading
There should be no doubt that clinical trials in Alzheimer’s disease and dementia need to be faster and more cost-effective if new treatments are to reach patients.
Public interest in participation in clinical trials for dementia is growing as governments become more vocal about the need to find treatments. A number of well-known organizations have well-established processes for linking patients with clinical trials. Alzheimer’s Association’s Trialmatch in the US and the United Kingdom’s Clinical Research Network (UKCRN) Study Portfolio allow patients to search for trials that they would like to participate in. In the case of dementia however, the disease may hinder a person’s ability to search for trials, potentially limiting access to experimental treatments. As research focuses more on prevention of Alzheimer’s it is important to include people interested in research who have no symptoms of memory loss. Continue reading
Testing drives drug development. From laboratory tests on patient specimens comes almost all of the clinical data needed for a new drug application. How and where those specimens are collected, transported, stored, and analyzed impacts the quality and usefulness of the data they produce. In the past, most tests were processed by local, academic, and specialized testing laboratories and coordinated by each investigator. However, centralized testing is becoming an accelerated trend – one that uses advanced technology and global operations to concentrate oncology clinical trial tests in a single, central laboratory.
The core value of a central lab is consistency. When local laboratories perform testing, their results will be different and results vary over the course of the trial. Central laboratory testing, on the other hand, offers ‘combinable data.’ The end product is that a result from a central laboratory is similar regardless of the global location where it originated from and the lab location where it is tested. At all of Covance’s central laboratories — in Indianapolis, Geneva, Singapore, Shanghai, and Tokyo — we generate data from the same analytical method platform, SOPs, equipment, reagents, and standards, eliminating variables that affect tests results. Continue reading
Over the last decade, the U.S. Food and Drug Administration (FDA), and other global regulatory agencies, have been placing increased scrutiny on clinical data quality. It has become clear that the traditional paradigms of sample testing management will not be sufficient in the future.
In order to avoid putting clinical trial programs at risk, the pharmaceutical industry will need to place a greater emphasis on meeting the new standards for testing data quality and documentation. The need to do so has become more pronounced with the increase in esoteric testing that has been seen in recent clinical trial programs. For example, the rise in genomics testing, immunohistochemistry (IHC) markers and flow cytometry panels has increased the volume of tests being sent out to referral laboratories. The frequency of warning letters from the U.S. FDA has also increased dramatically in the last few years. Continue reading
The gauntlet of oncology trial planning, investigation, and final approval can be daunting. Oncology is the largest, fastest-growing, and most research-intensive therapeutic area in drug development, yet the need for new agents is urgent. Plus, cancer patients are among the hardest to recruit for clinical trials.
Innovations in personalized medicine are also creating a dynamic environment presenting increased requirements for scientific and operational expertise; access to high-performing investigator sites with the right patients; and global combinable data. Continue reading
At Covance, we know that you, the pharmaceutical manufacturer, must deal with an increasingly complex marketplace. One of the current challenges is the 340B Drug Pricing Program (340B). In this article, we briefly review 340B and then discuss three aspects that affect you:
- The major challenges you face under this program
- Strategic recommendations for dealing with these challenges
- Important criteria to consider when selecting a partner to assist you with the 340B program
The 340B Drug Pricing Program
What is 340B?
The 340B program is a drug-pricing plan administered by the Health Resources & Services Administration (HRSA), a division of the Department of Health and Human Services (HHS). Eligible drugs include FDA-approved drugs, OTC written on a prescription, biological products that can be dispensed only by a prescription (excluding vaccines), and FDA-approved insulin. Continue reading