Therapeutic Development in the Absence of Predictive Animal Models of Nervous System Disorders: Proceedings of a Workshop by unknow

Author:unknow
Language: eng
Format: epub
Tags: Health and Medicine: Medical Technologies and Treatments
Publisher: The National Academies Press
Published: 2017-05-27T00:00:00+00:00

BALANCING INNOVATION AND INVESTMENT AT BIOTECHNOLOGY COMPANIES

Small biotech companies have a track record of pursuing innovative approaches in drug development, including using human models to evaluate therapies intended for human disorders, according to Martin. This approach follows a path taken more than 50 years ago, when imipramine, the first tricyclic antidepressant, was developed in the absence of a known mechanism of action or any kind of predictive model. Rather, over the course of 3 years, the compound was evaluated in more than 500 people with depression, providing a comprehensive description of the onset of action across different patient populations, diurnal effects, safety, and tolerability, in comparison to the standard of care, electroshock therapy. This study highlights the power of testing agents in humans as soon as reasonably safe and possible, said Martin.

Unfortunately, this serendipitous success has not been replicated in recent years, he noted. In 2010, pharmaceutical companies were developing more than 300 medicines to treat mental illness (PhRMA, 2010), but this number dropped to only about 100 in 2014 (PhRMA, 2014). Martin drew a sports analogy to explain the problem: while drug discovery engines in many companies generated numerous molecules, the process was more akin to “playing darts blindfolded” rather than producing many “shots on goal.”

Martin underscored the importance of risk versus cost trade-offs when considering whether to invest in a particular clinical development program. As illustrated in Figure 5-1, drug developers, especially those working in the CNS space, must ask whether proceeding through the various stages of development can be accomplished within a time frame that, if approved, will allow the molecule to be launched and commercialized before a loss of patent exclusivity. First, this requires answering questions about whether the compound will work, which often leads to a convergence around the same set of molecular targets as companies try to mitigate target validation risk, said Martin. Second, developers must ask whether the compound is sufficiently different from existing treatments to warrant the investment. Finally, they must determine whether there is a predictable path to approval. In answering this last question, companies may be faced with a choice of either following a regulatory precedent or investing in novel endpoints.

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