By Sara J. McKenzie, Principal, PharmaDirections, Inc.
Most entrepreneurs new to drug development are focused on demonstrating the pharmacology of their compound, and rightfully so. There is no point in spending years and millions of dollars in the development of something that does not have a chance of demonstrating efficacy in a clinical trial. Often, however, too little planning is done to position the investigational compound as an actual drug for the treatment of human disease.
Almost everything you do in the early development of your drug will set the stage for what the regulatory agencies allow you to do in your human clinical studies. If you have not yet developed the data package to assure the regulators that it is safe to administer your drug product to humans, particularly those in a specific indication, you will not be allowed to proceed.
The disease indication affects early drug development
Selecting the target indication is the very first step, and one that is well understood even by those with little past experience in drug development. Frequently the indication itself is the driving force in the search for the right compound; it is the desire to cure pancreatic cancer or eliminate Alzheimer’s disease or to address another devastating unmet medical need.
This is the easy part.
What comes next is the understanding of how clinical trials are conducted for that disease. Is there a well-recognized standard for the choice of a specific patient population? What is the accepted duration of the pivotal Phase 3 studies? Phase 2 studies? If there is no standard described by the FDA or other regulators, has a precedence been set by the study of other investigational agents? The answers to all of these questions will define the toxicology program that you must run. There must be a toxicology data package available which will support the duration of treatment prior to the start of a given clinical study. Additionally, the toxicology data must be generated using the same route of administration and the same dosing regimen as intended for the human clinical studies.
Physicochemical characteristics of your compound must be considered
The route of administration and dosing regimen are driven by the indication: the ideal compound is one that will compete against existing drugs on the market. If everything else treating the indication is oral, and once-a-day, your goal should be an oral, once-a-day formulation. This factor must be considered early, as your pharmacology studies and toxicology studies should incorporate the desired dosage form and dosing regimen as much as possible. Conversely, if your goal is a parenterally administered drug, your compound, with the necessary excipients, must be compatible not only with the tissue inside veins or arteries, but also with the IV administration sets that are used in hospital settings.
A clinical plan is required for an IND filing
Finally, even for your very first clinical trial, you must understand your overall clinical development plan. Each clinical study provides the data and paves the way for the next study. The single ascending dose (SAD) study in normal healthy volunteers sets the stage for the multiple ascending dose (MAD) study in healthy subjects. The MAD sets the stage for the Phase 1b study, which you may decide to conduct in patients. This in turn provides data for the dose determining Phase 2 study in patients. And so on.
Not only must your tox program and your dosage form and route of administration support your investigational drug filing, but also you must have already identified your Phase 1 unit(s) and principal investigator. Specific information regarding the clinical site(s) and the investigator(s) must be submitted at the time of the regulatory filing to obtain approval to begin administering your drug product to human subjects. You must also include the full clinical protocol for the initial Phase 1 study with the filing.
Thus you can see that it is critical to gain an early understanding of the clinical development path for your compound. The earlier you start, the better your chances of having a relatively clear and smooth path towards clinical trial success.
About The Author:
Sara J. McKenzie, PhD, MBA, has more than 25 years in the biotechnology and pharmaceutical industries, with hands-on experience in product development and program management.