Is this just green shoots or is it something more?

The drug development approach in neuropsychopharmacology based on ‘me too’ drugs has brought us to a deadlock and crisis some years ago with a disturbing decrease in interest in new brain disorder therapeutics. Fortunately enough, in recent years, we have started to see not only a re-emergence of early phase clinical trials of drugs with different mechanisms of action but also some new drugs that have made it all the way to the market.

Drugs that affect GABAA receptor modulation (and that have a different paradigm approach, i.e. episodic treatment for depression) and NMDA antagonists have recently been approved for disorders with no prior indications (postpartum depression or treatment-resistant depression). But a careful look at the pipeline of the few companies that have remained in the field of CNS or the ones coming back to it or the many new ones (welcome!) reveals a vast number of drugs with mechanisms of action different from the classical monoamines (e.g. drugs restoring excitatory and inhibitory signalling, PDE inhibitors, immunotherapy drugs, etc.). Drugs for orphan conditions, such as autism spectrum disorder (ASD) with mechanisms such as vasopressin receptor antagonism or sodium reabsorption inhibition in the ascending limb of the loop of Henle, are now in phase III trials. Public-private consortia are also fostering drug development in conditions such as ASD. The AIMS2-TRIALS project, the largest research grant ever given for neurodevelopmental conditions, is an excellent example (see https://www.aims-2-trials.eu/).

One of the most popular symposia at the annual ECNP Congress (Copenhagen, 7-10 September) is the New Findings Symposium, where eight speakers share innovative approaches and unpublished new results on treatments that may eventually come to the market in the near, or not-so-near, future. In a few months’ time, we will have the opportunity to discover promising new therapies for brain disorders at this symposium.

As we had the opportunity to discuss at our New Frontiers in Digital Health meeting, held in Nice a few weeks ago, which was oversubscribed and considered a great success by those who attended, the digital revolution will not only help pharmacological drug development (e.g. biometrics, validated apps with objective measures, algorithms to select the right population for a given drug, etc.) but will also produce new non-pharmacological treatments (some already awaiting regulatory approval after successful phase II trials for conditions such as ADHD). It is also the time for digital biomarkers, digital diagnostics, and digital therapeutics. By the way, make sure you mark your calendars for the next New Frontiers in Digital Health meeting that will be held in Nice on 8-10 March 2020 and will focus on how digital health is transforming clinical trials.

The high prevalence of brain disorders, the frequent lack of effectiveness of many existing therapies for their sufferers, and the burden caused by them make a re-emergence of interest in drug development inevitable. We must learn from past mistakes. We need all recent research findings (genomics, proteomics) to be transformed into brain targets that inform the development of new treatments for the identified contributory dysfunctions. A mechanistic approach. We need to move away from ‘blockbusters’ that will work on anyone and identify targets and biomarkers that may benefit groups of patients with a given identified pathophysiology (that may well cut across different disorders or be the cause of a given symptom within a disorder).

Exciting times. We are back again!

Celso Arango
ECNP President