FIGURE 2 - uploaded by David H Farb
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Drug approval by FDA since 1996. (a) Number of new drugs approved per year by category. Small molecules (gray bars) require the submission of a New Drug Application (NDA), while biotherapeutics (black bars) are reviewed under the form of a Biological Licence Application (BLA) (Data source: FDA Web site (www.fda.org)). (b) The drug approval differential, as compared to the number of drugs approved in 1996, reveals that there has been a progressive decline in approvals in the past 10 years. In the last few years, however, rate of decline seems to be leveling off. (c) Despite stabilization in the number of new drug approvals, the cumulative drug approval differential suggest that if approvals had been maintained to the level of 1996, we would have nearly 300 additional new drugs on the market today.
Source publication
In this chapter, we will provide a brief overview of some current therapeutic agents, including their weaknesses, and highlight selected opportunities for continued
drug discovery efforts in certain disease areas. We will then focus our attention on different strategies used to identify new therapeutic agents, comparing target -
based discovery (TB...
Context in source publication
Context 1
... by the FDA are classified as small molecules, whereas biotherapeutics account for 5-29% of the yearly approvals (Fig. 2). However, despite technical advances and increased spending in research and development by pharmaceutical companies (48), the number of drugs approved has been declining since 1996. This effect is particularly noticeable for small-molecule therapeutics. There are many reasons for this trend, including increased requirements for safety, ...
Citations
... We believe that three recent developments-the use of noninvasive imaging in human subjects to identify biomarkers implicated in neurologic disorders, and a convergence of pharmacologic effects in human populations of drugs that augment GABAergic tone or serotonergic tone, combined with the development of systems-based approaches to drug discoveryoffer a promising path forward. Systems-based drug discovery differs from traditional target-based discovery in that it utilizes an understanding of complex systems to search for potential therapeutic agents, as opposed to identifying agents based solely on interactions with a single target (Desbiens and Farb, 2012). ...
... Although traditional target-based discovery has shown success in identifying new drugs against previously validated targets, the reductionist nature of this approach often leads to late-stage failure when the drug is assessed in increasingly complex systems. By contrast, a systems-based approach may speed the drug discovery process by focusing less on drug interactions with single targets and more on systems-level assays representative of the disease (Desbiens and Farb, 2012). ...
Anxiety disorders are a major public health concern. Here, we examine the familiar area of anxiolysis in the context of a systems-level understanding that will hopefully lead to revealing an underlying pharmacological connectome. The introduction of benzodiazepines nearly half a century ago markedly improved the treatment of anxiety disorders. These agents reduce anxiety rapidly by allosterically enhancing the postsynaptic actions of GABA at inhibitory type A GABA receptors but side effects limit their use in chronic anxiety disorders. Selective serotonin reuptake inhibitors and serotonin/norepinephrine reuptake inhibitors have emerged as an effective first-line alternative treatment of such anxiety disorders. However, many individuals are not responsive and side effects can be limiting. Research into a relatively new class of agents known as neurosteroids has revealed novel modulatory sites and mechanisms of action that are providing insights into the pathophysiology of certain anxiety disorders, potentially bridging the gap between the GABAergic and serotonergic circuits underlying anxiety. However, translating the pharmacological activity of compounds targeted to specific receptor subtypes in rodent models of anxiety to effective therapeutics in human anxiety has not been entirely successful. Since modulating any one of several broad classes of receptor targets can produce anxiolysis, we posit that a systems-level discovery platform combined with an individualized medicine approach based on noninvasive brain imaging would substantially advance the development of more effective therapeutics.
