CNS Therapeutics: Is the Risk Worth the Reward?

More than $2 trillion dollars a year are spent on treatments for CNS disorders. One in three people over 80 currently has Alzheimer’s disease. With the aging population increasing, the number of affected people and costs associated with their care and treatment are expected to rapidly increase. Neurological disorders are a major public health concern. Not surprisingly, pharmaceutical companies have focused a significant portion of their development pipelines into developing CNS therapeutics. However, CNS drug development has not produced the expected blockbuster yet. Previously, we discussed the scientific advancements that are required to support development of CNS therapeutics. Here we discuss the challenges facing drug development for neurological disorders.

Reasons for major CNS drug failures

1. Increased risk, decreased approval rate: CNS drug development costs more and takes longer than developing treatments for other therapeutic areas. In large part this is because treating brain disorders involves increased risk. The trials take almost twice as long as trials in other therapeutic areas. Patient recruitment and compliance throughout the trail is difficult. Drug candidates fail late in the drug development process, with several recent candidates failing in Phase III clinical trials.
2. Clear endpoints in clinical trials for neurological disorders are lacking: A major hurdle is the lack of understanding of disease and drug mechanism. For antidepressants, the major classes of drugs selective serotonin reuptake inhibitors (SSRIs) work broadly and have no clear disease altering mechanism suitable for monitoring. Readouts for trials usually involve outdated assessment criteria and ambiguous endpoints. With clinical depression, the readout is often patient questionnaires. Similarly with Alzheimer’s disease, clear diagnosis is difficult, there is no way to assess advancement or stage of disease other than clinical criteria, and perhaps treatment once a patient is symptomatic is far too late.

There is a striking need for diagnostics to visualize, assess and quantify effects of CNS therapeutics. These tools are maturing, as discussed in part 1 of this series, preparing the way for these blockbusters to come to fruition. A clear example of the progress the field is making can be seen by the development of genetic and animal models for CNS disorders that are now available.

While there have been some serious setbacks for development of CNS therapeutics. The reward for developing therapies to treat CNS disorders still promises to outweigh the risk. Pharmaceutical companies are rethinking the way they are approaching this challenge in the wake of several big failures. In the next post of this series, we discuss the new models that the pharmaceutical industry is using to decrease risk and increase the risk of bringing the next blockbuster to market.