Last week, BIO published an exceedingly interesting report, entitled The State of Innovation in Highly Prevalent Chronic Diseases: Depression Therapeutics. The press release and report are available here.
This and future reports will examine the state of innovation in some high prevalence therapeutic areas, such as depression.
The report is fairly short, and we encourage you to peruse it.
A few points caught our attention:
Few Drug Candidates – According to the analysis, only 29 NCEs have been approved for depression since 1959. 1959!
Limited Innovation – All of these agents essentially follow the same pharmacology: modulation of the brain’s monoamine neurotransmitter levels. There have been four phases of innovation, beginning with the approval of imipramine in 1959. The Tricyclics and bupropion emerged in the 1970s and 1980s. The SSRI/SNRI era began in 1987 with the approval of fluoxetine. Lastly, over the past decade or so, more specific agents have been developed.
Other targets have been pursued, such as neurokinin receptors and glucocorticoid receptors, but none of these have achieved clinical success.
And that’s it.
Can you imagine this happening in other therapeutic areas, like oncology? Imagine having various leukemias being treated today like they were in 1959?
So, what’s going on?
Translational Difficulties – Depression is one of several areas where it is exceedingly difficult to translate positive Preclinical data into Clinically effective candidates. While Phase I probabilities of success are comparable to other indications, Phase II probability of success in depression is only 20%, compared to 31% for all indications.
Small Pipeline – According to the report, there are only 33 programs in clinical development for depression. This will not improve in the near-term, as there are only 11 programs in Preclinical development, of which only 4 out of the 11 are novel drug targets. Venture investments in companies with candidates targeting depression is minimal.
Commercial Difficulties – Depression is a market which is heavily genericized, making reimbursement very difficult without very large, compelling clinical data.
How do we solve this problem?
To say that the brain is an unbelievably complex organ goes without saying. But, we had this same problem in oncology. Over many decades, we have collectively understood what is happening in many cancers at the molecular and genetic level, resulting in an amazing multi-decade wave of innovation.
it is likely that similar levels of understanding will be needed before true innovation takes place in this field. Biomarkers and genetic biases, for example, may yield additional avenues for target identification and validation (reviewed by Niciu, et al.).
But until that happens, we may be in a multi-decade phase in which patients suffering from depression will continue to face their condition without innovative novel therapies.