Drug development is a continuous process. Specifically, there will always be drugs in preclinical development and more advanced ones in clinical trials. These medicines are typically exorbitant in cost due to a variety of reasons, the most important of which is their small production volume coupled with the need to recoup the hefty investment needed for their development, a timeline that could stretch to 10 and 15 years depending on the difficulty of developing the drug and the success of animal and human clinical trials (Phase 1, 2 and 3). For each new drug filed under the New Drug Application provision with the Food and Drug Administration (FDA), many will not make it through Phase 2 or 3 clinical trials, having failed the safety and efficacy tests. Phase 1 trials evaluate the safety of the new drug, while Phase 2 further evaluate the safety as well as efficacy of the medicine. Phase 3 is make or break: given its testing in patients who need the drug as a last option since all other treatments possibilities have been evaluated.
Take cancer immunotherapy as an example, the drug discovery process relies on basic science research that reveals the possibility of using antibodies to recognize and inactivate (through binding) specific protein receptors on the cell membrane necessary to prevent excessive expansion of immune cells that recognize, for example, cancer cells, and thus unleashing the immune response on cancer. Using the immune response to recognize and attack cancer cells is not something novel from nature’s perspective, given the fact that many cells in the body accumulate mutations through its life and some of them escape programmed cell death (e.g., apoptosis). But some cancer cell types are capable of inactivating the immune cells that, in normal circumstances, kill them. Though not all mechanisms are known, the primary means that cancer cells are able to keep the immune system quiet is through secretion of factors that prevent the recognition of cancer cells by immune cells, for example, by binding to specific cellular markers on cancer cells.
With basic knowledge of inhibiting specific cellular markers that inactivate cell division of immune cells, these antibodies inhibitors serve as leads for further rounds of validation at the cellular and tissue level prior to animal trials that seek to confirm the utility of these molecules on disease treatment. The steps through which the process flow is arduous and incur significant amount of time and effort, due to the need to progressively expand the scale and level of details, ranging from molecular and cellular assays, to animal studies and population level validation of targets and leads.
If the candidate drug is able to progress through animal studies for validating the treatment outcome, it will move on to preclinical studies to ensure that, at the animal model level, there is little or no safety or toxicity risk. Following on from these experiments would be clinical trials aimed at establishing safety and efficacy of the drug in humans.
A point that must be noted is that many drugs failed at various stages of the drug discovery and development process. Many biotechnology startups that based their financial viability on one or two candidate compounds that ultimately fail, have to exit the biotech scene given the punishing nature of the industry where the fortunes of companies (even large pharmaceutical companies) rely on one or a few blockbusters drugs (defined as drugs with annual revenue of more than US$ 1 billion).
Collectively, it takes about 10 to 15 years to develop a drug target into a compound suitable for human use in the clinic for treating disease, and along the way, many candidate drug compounds failed at different stages of development for a variety of reasons. Together with the failed compounds (for reasons of toxicity and poor efficacy) come the downward trajectory of many companies, many of which are biotechnology startups based on a single compound lead for treating a specific disease. With such a high failure rate, drug discovery is a high risk endeavor only suited for well funded and capitalized companies. Large number of experiments (both cellular and animal and ultimately human clinical trials) necessary to validate and demonstrate the safety and efficacy of specific compounds meant that, at the onset of a new drug’s entry into the market, it can only be marketed at a substantial price for recouping significant cost during its development. For drugs whose target market is small, such as those developed for treating genetic diseases that afflict a small proportion of the population, the price of the new drug would be so high that, without subsidy from insurers or a national healthcare insurance plan, its affordability is highly questionable.
Category: drug discovery, medicine, structural biology, health, cancer, biotechnology, biochemistry,
Tags: drug development, clinical trials, lead compound, candidate compounds, safety, efficacy, high throughput screening, preclinical trials, compound libraries,