Less Gambling, More Science: Phase II Under Scrutiny


Failures of Phase III programs after successful Phase II programs is probably the worst outcome of a clinical development program, as it failed in the most costly way. Nevertheless, these failures occur not infrequently. In psychiatry, highly publicized Phase II success stories ended in discontinuations of development programs, such as the NK1-antagonist program in depression several years ago. More recently, other examples have emerged. Some skip the Phase II process altogether with designs, which are supposed to provide “pivotal” data for regulatory purposes in large Phase III-like studies, which are just labeled as Phase II. These failures do not come out of the blue. Sometimes it is important to go back to basics and consider the purpose of Phase II trials.

What is the purpose of a Phase II trial?

The purpose of Phase II trials, besides gaining insights into the safety of a compound, is broadly exploratory, i.e. to generate data, which help with the design of the pivotal Phase III program. In a therapeutic area, a reasonably performed Phase II study can provide insights into clinical and biological patient characteristics, which match the properties of the drug under study.  With an increased interest in personalized medicine, these boundaries between patient populations have to be understood in order to be successful. This approach is in direct contradiction to the urge to generate a “pivotal” Phase II outcome. Continue reading

CNS Drug Development: Impact of Biosimilars

neuro2The biologics sector continues to offer lucrative opportunities for future growth, but with relatively few contributions for the treatment of CNS indications. High-growth CNS market segments generally share one feature: biologics play a pivotal role in the treatment paradigm, or soon will. Neuromuscular-blocking biologics recently secured regulatory approval for chronic migraine. Alzheimer’s disease is a high unmet need indication currently addressed only by symptomatic treatments, with potential for disease modification biologic therapies to play an important future role.

The example of biologics’ success in the CNS market is highlighted largely by the success of therapies that target the multiple sclerosis (MS) disease process. This success has spurred some drug developers to increase their assets in this space and seek future opportunities for biologics in other CNS diseases. However, one important new reality that is slated to reshape the future landscape of this market is the introduction of biosimilars. Continue reading

Simple Strategies for Balancing Risks in CNS Drug Development

neuroDrug discovery and development is inherently risky. Recent figures indicate that less than 11% of new pharmaceutical agents entering clinical development reach the marketplace across all therapeutic areas. For those working in CNS drug development, we know well that the prospect of seeing our compounds passing through all phases of drug development and successfully reaching the market is even more challenging.

This low success rate in CNS drug development has been attributed to a number of reasons, among them the complexity of the brain physiology, the limited characterization of the pathological mechanisms leading to neuronal dysfunction or the suboptimal knowledge about the mechanism of action of drug candidates by the time the compound enters clinical development. Continue reading

Harnessing Public Involvement for Faster, Lower Cost Trials in Dementia

neuroscience graphicThere 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

Addressing the Challenges of Abuse Liability Testing – Meeting Regulatory Requirements and Study Design

Addressing the Challenges of Abuse Liability Testing – Meeting Regulatory Requirements and Study Design

Identifying clinically useful compounds and developing a novel drug treatment to improve human health has many rewards. But with increasing press about the growing abuse of prescription medications and potentials for physiological or physical dependence, regulatory agencies around the world have taken note.

Called abuse liability testing, this stage of drug development was first officially recognized in 1970 with the U.S. Controlled Substances Act. Since then, many iterations and guidelines have been developed to determine a compound’s potential for abuse.

Abuse liability studies are very important because they are required by the regulatory agencies in U.S., Europe, and even Asia for setting the scheduling of new chemical entities that come into the marketplace. Continue reading