The heart of drug attrition
It’s well-known that the time and cost to bring a new pharmaceutical to market are considerable. The average length of time from target ID to a new therapeutic is about 13 years and costs roughly $1.5 billion, embedded within an overall failure rate of 95%. But why?
When you ask scientists and biopharma leaders about the source of high drug attrition rates, they give many factors. However, the lack of “translatability” is most frequently cited as the root of the problem. Lack of translatability can come in the form of the failure of preclinical models to predict efficacy, safety issues with compounds, or not treating the “right” patients. All of this ultimately comes down to points within this process being foggy or lacking critical information.
We recently had two senior research executives from a Top 5 pharmaceutical company share their thoughts on attrition and how metabolomics is turning the tide.
David Morris, vice president of R&D, said, “Many of the programs
that we start, for one reason or another, do not make it through to the
clinic. Part of the reason is that we don’t have a suite of
technologies that allow a pretty good predictive analysis of what will
and will not be successful.”
So, how does one achieve greater clarity across the drug development process? How do you know for certain that directing a compound against a target will combat the disease in humans without compromising safety? Ultimately, choosing the right target comes down to deep understanding of human biology – knowing that a target is relevant to disease, that relevant preclinical models reflect salient aspects of the disease and target biology, and that hitting the target will positively affect the disease without undesirable side effects.
“Any technology that allows that reasonable prediction is going to be highly valued by pharmaceutical R&D workers,” continued Morris.
No clear path
Pharmaceutical companies are constantly bombarded with “the next great thing” that will revolutionize drug discovery or reduce attrition. Clearly, while many technologies have been useful, none have fully delivered on the promises.
“There is a tremendous suite of tools available to most pharmaceutical R&D researchers...everything from genetics, genomics, imaging, structural biology, rational drug design,” said Morris. “The challenge is that in combination, many of them will point in a direction, but none of them will give an unequivocal positive or negative about the outcome.”
Metabolomics points the way
Metabolomics, however, provides comprehensive, actionable insight into each stage of the drug development process that allows drug researchers to assess safety and efficacy (as well as their associated biomarkers) and make meaningful decisions across the development process.
Jon Williams, a senior technology director at the pharmaceutical company, said, “The best part about metabolomics is that you can see signals for both safety and efficacy at the same time. And, if you can see that, you can [say] this compound’s effective, but it doesn’t look like it has the right safety signals. Let’s kill that compound.”
Because metabolomics creates a comprehensive snapshot of the phenotype and aggregates all the activity of the organism and the influences on the organism like a drug treatment, it is proving itself to be a powerful source of information to help build confidence and discharge risk.
“The beauty of metabolomics is that it lets the body do the work and essentially integrates all of those functions. And, what you get is an aggregate yield of all the changes that the body has actually undertaken. What you’re seeing is the end product of a lot of different interactions biochemically, cellularly, in the body, to yield that metabolomic profile,” said Morris.
Williams added, “If you do not have metabolomics expertise, it’s a very tough field to build into. We had some institutional knowledge of metabolomics…and had done an internal effort before, and actually had shut it down many years ago. So, the partnership [with Metabolon] made sense.”
In closing the video, Morris said this about metabolomics, “It’s a very powerful technology. And, if I had to take my toolbox, empty it out, and think about what tools I would put back in there, I can honestly say that metabolomics and Metabolon’s platform would be one of the first that went back in that toolbox. I view it with that level of importance.”
To put metabolomics to work for your R&D efforts, please contact us.