The Rx Pipeline – Has The Spigot Been Turned Off?

A recent article in the New York Times by Cornell psychiatrist Richard Friedman lamented the fact that there isn’t much in the FDA pipeline regarding the development of novel drugs for mental health use. In his op-ed, Friedman blamed Big Pharma for a “crisis in drug innovation.”

Case in point: last year, the FDA’s Center for Drug Evaluation and Research approved almost forty new molecular entities (NMEs) – the highest number of such applications in more than a decade. Given the green light were agents for some exceedingly rare diseases, malignancies of all sorts, and cardiovascular pathologies. Yet with the arguable exception of Amyvid, Abbott’s new compound for the imaging of β-amyloid plaques in the brain (Alzheimer’s), none of these NMEs have known or intended psychiatric application.

[I say ‘known or intended’ since over the years many psych meds have been discovered serendipitously, though I hate for my profession to depend solely on serendipity for its advances]

There has been a recent spate of clinical trials in which potentially novel antidepressant and antipsychotic agents failed to show efficacy greater than that of placebo – sometimes as late as Stage III in development – and Big Pharma is suspected of having concluded that psychiatric drugs are just too uncertain and too risky to pursue. That’s not to mention also too expensive: estimates range to almost $2B, and up to 15 years, to develop and market a new drug. Glaxo Smith Kline has accordingly shuttered its psychiatric labs altogether. And as of this writing, both AstraZeneca and Pfizer have markedly scaled back their investments in CNS R&D.

Granted, psychiatric disorders can be chronic, recurrent, likely multi-factorial in etiology, and complex beyond our current comprehension of neuroanatomy and neuropathology. And while I personally do not support such testing, for better or worse, there is a dearth of animal models with the requisite validity to predict eventual human clinical outcomes. That being said, it is still sobering that almost all of the current psychotropics being prescribed in the United States share the same molecular targets in the brain as did their ‘primitive’ precursors from the 1950s and 1960s.

What we’re seeing in lieu of meaningful advances is a rush of what psychiatrist Daniel Carlat has labeled ‘Me Too’ drugs, those with nearly identical molecular structures and proposed mechanisms of action very similar to agents already on the market; there’s no new ground being broken thusly. And then there are the rebrandings of earlier drugs: approved antidepressants and antipsychotics attempting to win ‘official’ FDA indication for other conditions – anxiety, bipolar mania, refractory depression, chronic pain – despite the fact that off-label prescribing is already permitted and widespread.

All is not entirely dismal, though. Ketamine, a widely-prescribed anesthetic, has been shown to have powerful antidepressant effects (there’s that ‘serendipity’ thing again). And we now have a more thorough grasp of the pathophysiologies of certain CNS disorders, opening doors for further industry and academic research and collaboration. These conditions include those of the addiction spectrum, Fragile X Syndrome, pain states, and insomnia to name only a few.

Of course, this also raises the issues of intellectual property rights and patent protection, the subjects of future posts.

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