Wither Neuroscience R&D? Pfizer’s Ehlers Doesn’t Think So
In this week’s issue, I look at the perceived exodus by pharma companies from neuroscience R&D. Between AstraZeneca’s recent cutbacks, the closure of Novartis’ neuroscience research facility in Basel, and earlier moves by GSK and Merck, industry watchers are understandably worried that the neuroscience pipeline will dry up.
One person who isn’t worried is Michael Ehlers, Pfizer’s chief scientific officer for neuroscience research. Ehlers came to Pfizer a year and a half ago from Duke, with the explicit mission to revamp how the company finds and develops drugs for brain diseases. The scientist is convinced that the field is ripe for new and better drugs, and that by staying in the game, Pfizer will be in a good position to capitalize on what he believes will be a healthy flow of new discoveries.
Many drug companies argue that the risk in neuroscience simply doesn’t justify the investment. The overarching sentiment is that the brain is still a black box: good targets are few and far between; clinical trials are long and unpredictable; regulatory approval is tough; and generic competition is plentiful. For many big pharma firms, the math just doesn’t add up.
“I personally don’t find that calculus to give you the total picture,” Ehlers says. Shifting resources away from neuroscience to focus on areas like oncology, where the environment looks favorable—clear clinical trial endpoints, the opportunity for fast-track approval, an easier chance for reimbursement from payors—only makes sense in the short term, Ehlers says. But that thinking “is short sighted as to where the fundamental state of biology is in neuroscience,” he says.
Why is Ehlers so encouraged about a field that so many are walking away from? He believes that neuroscience is poised to benefit from the kind of genetic links that generated so many targets—and eventually so many targeted-drugs—in oncology. “There is going to be kind of a revolution in the next five years—it’s not going to be tomorrow…but you have to think about that inflection of opportunity over the five-to-ten year time horizon.”
To take advantage of each new genetic clue, Ehlers has revamped Pfizer’s approach to neuroscience R&D. As this week’s story explains:
In the past, big pharma often gave its scientists a mandate to work in areas such as Alzheimer’s or schizophrenia, regardless of tractable drug targets. Now at Pfizer, Ehlers says, his team is “indication agnostic.” Any program that Pfizer undertakes must have a critical mass of biological knowledge—for example, human genetics, human phenotyping, and evidence of dysfunctional neurocircuits—to convince Ehlers it’s worth pursuing. “We start there,” he says. “That hasn’t always been the case.”
Moreover, Pfizer no longer relies on mouse models as predictors for responses in humans. “We’ve for the most part stopped all rodent behavior as a model for disease and are much more about what’s happening in the brain,” he says. Scientists measure human responses to prove experimentally that a drug works.
Pfizer’s goal, according to Ehlers, is to tackle fewer projects but have more confidence in their potential for success. The result should be a drug pipeline “rooted in something more than optimism.”
He cites Huntington’s disease as one area that, even before coming to Pfizer, he saw as a prime scientific opportunity. “You know the gene, you know a fair bit about what’s going on, you have a wealth of data, tons of models, a clear clinical course, and an identifiable patient population,” he says. “If we can’t deal with that, we’re in trouble.”