Pharma and the Food and Drug Administration are stuck in a stalemate over pharmacogenomics. Determined to put pharmacogenomics technologies to use in drug discovery, the FDA, desperate for edification, has asked pharma to submit voluntarily certain genotyping and gene-expression data.
But pharmas, fearing these data may reappear downstream to bite them on the bottom line, are reluctant to give them up. As a result, insiders have resigned themselves to the belief that significant pharmacogenomics-driven regulatory breakthroughs are at least 10 years away.
Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, is out to prove them wrong. As a first step, the director has extended what amounts to an olive branch that she hopes will restart the FDA’s sputtering pharmacogenomics initiative.
“The first thing that’s happening is that we’re all taking a deep breath and we’re going to see over the next few years what this technology can really do,” she told SNPtech Reporter. “Because it’s not really paying off yet.”
Woodcock said that from her perspective drug companies will have to wait five years before pharmacogenomics technologies create personalized therapeutics or even reduce the cost of clinical trials. “It’s not going to lower the cost or really improve drug therapy over the very near future,” Woodcock conceded. However, “I think that over the middle future it’s going to reduce the cost of drug development in selected cases — possibly remarkably.”
She stressed that these two bulwarks of pharmacogenomics — less costly clinical trials and better drugs — will likely emerge “hand in hand.” First, however, the FDA needs to learn, and pharma needs to trust it enough to teach it.
These days, Woodcock’s department is writing a draft guidance for industry it hopes will encourage more pharma companies to submit greater amounts of genotyping and gene-expression data culled from pre-clinical research. Woodcock said she expects CDER to have a draft ready for public comment this summer, and a final version in industry’s hands in the fall. “We need to ... get this [issue] settled,” Woodcock told participants of the 6th annual Pharmacogenetics and Medicine Lectures at Yale University last week.
If pharma bites, and begins uploading reams of pharmacogenomics data, the FDA will get its hands on information it will likely use to set policy. “What we’re really talking about here is what needs to be submitted and what doesn’t need to be submitted, and how this information will be used — or not used — for regulatory decision making,” she said. “This is the key.”
But pharma has traditionally been leery about showing the FDA its early-stage data, and especially toxicology data, which have the distinction of being pharmacogenomics-heavy. In large part, pharmas fret that showing the FDA exploratory genotyping or gene-expression data will spur the agency to demand additional costly trials — which is anathema to pharmacogenomics. “Industry is afraid we will over-interpret these data in a way that will be harmful for drug development or it will slow down their drug development,” Woodcock said.
Some large drug makers exhibit these concerns. For example Pfizer, which commands 11 percent of the world’s market for prescription drugs and will spend close to $7 billion on R&D this year, said it opts out of submitting certain early-stage data. Bruce Littman, executive director of clinical sciences at Pfizer’s global R&D unit, admitted at the Yale conference that Pfizer actively shies away from submitting early-stage toxicology data for fear that some of the data, like those that depict activated proto-oncogenes, may be used against it down the road.
Woodcock stressed that this concern is unfounded, and said she hopes the impending guidance will adjust pharma’s perception: Early-stage gene-expression studies in many drugs will activate proto-oncogenes, she explained. In fact, many drugs that have been on the market “forever” and are “generally regarded as safe” have activated these genes. “That’s the kind of context that’s so important to build around understanding these data,” Woodcock told SNPtech Reporter. “And if we don’t get information from all the companies, and if they don’t publish it generally, then it’s not going to be available in a way that’s going to help us all learn how to understand this data.”
Pharmas don’t know what the data mean, she said, and they “are distrustful of what the regulators think of it.” Eventually, she went on, this information “will become important and meaningful — we all hope. We would like to have people here [at CDER] become familiar with these data and techniques, both the good and the bad. But we need to reassure the industry and make them feel very comfortable that we’re not going to therefore use that information in our decision making about their product.
“We’re on the horns of a dilemma here, and there will be some degree of trust established,” she added. “It seems that the time is right now.”
To be sure, the FDA currently has a safe-harbor policy that allows pharma companies to “submit exploratory genetic and genomic data that would not be part of the traditional regulatory decision-making on applications,” Larry Lesko, director of the FDA’s office of pharmacology and biopharmaceuticals said in an earlier interview. “We think a guidance for industry would be helpful, and we realize it is important to have a guidance that is general enough to allow the technology to grow and yet be able to say something to encourage firms to use and apply the information.”
For her part, Woodcock said she has instructed her department to create a pharmacogenomics group whose job will be to review pharmacogenomics data submitted by drug companies. However, the organization is still in the early stages, and Woodcock said she still must decide how to fashion it. This new group will likely be independent from the 2-year-old pharmacogenomics working group led by Lesko, which works on policy. It was not clear when Woodcock’s working group would be created.
Robert Rubin, a professor at the Massachusetts Institute of Technology’s Program on the Pharmaceutical Industry, said the FDA is on the right track — “Janet Woodcock’s heart is in the right place” — but suggested that industry’s wounds run deep.
“This is something that’s going to have to evolve. Everybody is suspicious of everybody else, and the whole system has been an adversarial one for too long,” Rubin told SNPtech Reporter. “The industry has some issues. … I don’t think any of us are well served by paranoia.”
Woodcock, in response, said that “in the past, the relationship [between the] FDA [and] the pharmaceutical industry was somewhat adversarial, [but] this has eased in recent years.”