When Daria Mochly-Rosen, PhD, was preparing an upcoming talk about drug discovery and development for Stanford's Summer Science Lecture Series, she ran into a friend in Palo Alto. As their conversation turned toward her presentation - Mochly-Rosen wanted to discuss the factors that make drug development time-consuming and expensive - her friend replied, "This is going to be a very short talk. Why are drugs so expensive? Greed!"
But in her talk late last week, Mochly-Rosen, a professor of chemical and systems biology at the medical school, outlined another explanation: Drug development takes time and money because it's difficult and failure is a strong possibility.
"When we're making drugs, we have to be better than nature," Mochly-Rosen said.
Consider a few basic requirements of the process:
- Discovery: Identify the molecular basis of disease; find a molecular target; find a key (a protein, for example, that binds to molecular target and prevents molecule from performing its normal function); make sure the key doesn't fit other keyholes that open pathways to unwanted outcomes.
- Preclinical testing: Assess the drug in animals to make sure that it's effective in an animal model of the human disease and that there are no side effects. Somewhere between one of 10 and one of 100 projects successfully pass these tests and can move from this stage to clinical trial.
- Phase-1 clinical trial: Determine that the drug is safe in humans.
- Phase-2 clinical trial: Determine optimal dose.
- Phase-3 clinical trial: Look for statistically significant benefit. (Can involve 10,000 to 30,000 patients.)
The total cost of that process for one drug is estimated to fall between $500 million and $1.2 billion. The chances that a drug will fail at any of the stages of development are enormous. Each year, only about 20 new drugs are approved. Fifteen of those are in a class called "me-too" drugs because they replicate what other medications already do.
After her own foray into industry, Mochly-Rosen concluded that pharmaceutical researchers are too familiar with failure, and as a result, they're risk-averse. But on the other hand, academicians often are not even aware of what should be done to ensure that their ground-breaking discoveries translate into practical applications; their findings may not move beyond the pages of Science or Nature.
Mochly-Rosen's solution? SPARK, a Stanford program that brings together academicians and industry experts who volunteer their time to help projects that have great potential benefit to society.
The program is not only training graduate students and postdoctoral scholars to package their work so that it's more useful to industry: it's also producing results. Coming soon from a SPARK program near you: a hepatitis C treatment that has been shown to lower the virus load in patients.