The Druggable Drug
Regina Kelder

The Druggable Drug

Advice on improving the probability of your drug's success, from someone who has been there

Getting a novel drug to market is a bit like finishing first in the Boston marathon. It's the ultimate victory in a long, expensive journey. The question is: How many actually succeed?

It's a fact that new compounds, be they best-in-class or first-in-class, are pretty rare events. By some estimates, only 5% of all the experimental drugs tested in humans are found to be safe and effective. Other groups place the odds a bit higher—around 10%. And the ones that do succeed take 8-10 years to move through the pipeline and cost companies a small fortune. (One widely cited figure from the Tufts Center for the Study of Drug Development suggests it now costs US$2.6 billion to develop and win marketing approval for a new drug.)

Elizabeth Stoner, managing director of MPM Capital, a Boston venture firm that focuses on the life sciences with extensive experience in pharmaceutical development, compared the interwoven process of drug development to a pearl necklace. "If one of the pearls gets loose and the whole strand falls apart" your product is doomed, she said during the kickoff of a May 5 workshop on how to optimize the drug development process. Charles River Labs sponsored the event, a soup-to-nuts discussion that touched on many of the hot-button topics in translational research. The seven speakers from CR and the outside, offered real-life examples and case studies on how to improve the efficiency and, perhaps more importantly, probability of moving one's product forward.

No one enters the drug development business thinking their product will fail, Stoner told the audience of mostly biotechs and microtechs. "We all truly believe what we work on has a much better probability of success. I have seen a lot of things go awry, but good things happen, too."

Stoner advised the group to be ambitious. "Those days of little formulation changes are kind of over, in my opinion," she said. "You need to dream big on providing something innovative. That is where the payers will look and regulatory agencies as well."

Stoner says investors also want to be sure that a drug developer has done the right experiments and has sufficiently pressure tested its drug early on in the development process. "One of the things I see is a fear of doing that filler experiment. It may be a killer, but the sooner you do it the better," she said. "Don't be afraid to take the dose up—that's the time to press because that is where you will see if there are any safety problems."

Other observations from Stoner:

  • Confidence in biotechs. There are some very good generics serving a large proportion of the population, she says, but they don't serve everyone. There is still room for innovation and a great need for orphan drugs.
  • Making a drug "druggable." It's critically important, early on, to demonstrate specificity in target engagement—do you have a hypothesis for a mechanism and not just an observation. Other points to consider early on: Can the product be manufactured, is the delivery of the drug feasible and will it interfere with other key metabolic pathways.
  • Phase 1 studies. There is an increasing trend supported by the regulatory agencies to start doing Phase 1 studies in target populations rather than in the general population. These early-stage studies will still require relatively healthy individuals, of course, but enrolling patients that the drug is designed for offers more relevant safety data. It will also help accelerate the research. Having good pharmacokinetic data (PK) will be key, though.
  • Biomarkers. Clearly these are important for demonstrating the efficacy of a drug early on, says Stoner. For diseases like diabetes, there is an inherent biomarker—blood glucose. But for others, there are no biomarkers. The mechanism of action can't be easily measured. It's not ideal, but this doesn't have to be a show-stopper, says Stoner. In these cases, good PK will be key.

How to cite:

McEnery, Regina. The Druggable Drug. Eureka blog. May 7, 2015. Available: