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FDA Official Hints That Proteomic Data Should Play Role in Agency's Pharmacogenomic Plans

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In what could become a significant step forward for proteomic researchers and tool vendors, a senior Food and Drug Administration official last week suggested that the agency's Voluntary Genomic Data Submission guidance should be updated to include proteomic and other kinds of biomarker data.

Larry Lesko, director of the Office of Clinical Pharmacology at FDA's Center for Drug Evaluation and Research, told participants at the Drug Information Association's annual meeting in Philadelphia last week that it may be time for the agency to "rethink" the VGDS program.

The development is significant because until now, no FDA official at Lesko's level had intimated that proteomic data could play a role in personalized medicine. It is particularly noteworthy because the agency had expressly left out any mention of proteomics in its pioneering pharmacogenomics guidance two years ago [see Pharmacogenomics Reporter 03-04-04].

The FDA enacted its VGDS program in 2004 as a way to learn how drug makers use various pharmacogenetic technologies. At its most basic, the program is a kind of safe haven that encourages drug makers to voluntarily submit genetic data from clinical trials so the FDA can expand its own knowledge about the science, platforms, and methodologies. In exchange, the FDA pledged not to use the data in its review process. The VGDS deals only with genetic data.

At the DIA conference, Lesko suggested that the VGDS program be expanded to include proteomic, metabolomic, and other kinds of biomarker data. He took care to note that these views were his, and that he was not speaking for the agency.


"I think the FDA has become more proactive than any agency, and especially any regulatory agency. I think that people [at the FDA] do understand that genetics, while it is an interesting biomarker, is not the be-all, end-all."

Lesko suggested that "VGDS" be replaced by "VXDS" in which "X" could refer to proteomic, metabolomic, or other biomarker data. This suggestion was originally reported last July in ProteoMonitor's sister publication Pharmacogenomics Reporter, which quoted Felix Frueh, associate director of CDER and head of the agency's Interdisciplinary Pharmacogenomics Research Group, saying that the agency is "open-minded" to reviewing proteomic biomarkers [Pharmacogenomics Reporter 07-07-05] But Lesko's comments carry more weight because of his seniority and broad influence at the agency.

To be sure, Lesko's comments do not signal any concrete movements within the FDA that would result in a proteomic guidance document. Rather, they were uttered to put the industry on notice that the agency may soon be willing to begin formally studying proteomics' place in pharmacogenomics.

Lesko's comments don't signal a "tipping point" but rather "another incremental step" Keith Batchelder, founder of consultancy Genomic Healthcare Strategies, told ProteoMonitor this week. "I think the FDA has become more proactive than any agency, and especially any regulatory agency. I think that people [at the FDA] do understand that genetics, while it is an interesting biomarker, is not the be-all, end-all."

Batchelder, who was an Oak Ridge Fellow at the FDA's Center for Devices and Radiological Health a few years ago, said he believes the agency is starting to understand more clearly that "you need to look at all the potential biomarkers and which ones are important. Some of the proteomic biomarkers are not going to be important just as some genetic biomarkers are not going to be important," he said.

"But there are obviously going to be genetic and proteomic biomarkers that in combination will become incredibly sensitive and specific in terms of prediction [and to] response to therapy; all of those things that are important," he added.

"In some sense, it doesn't surprise me that the FDA is now looking at proteomics, because if you look at the science, that's where it's going to drive you; you are going to end up needing biomarkers from a whole broad array of omics."

Voluntary Milestones

Since it began in March 2004, the Voluntary Genomic Data Submission program has had 25 data submissions that have resulted in 15 industry meetings, Larry Lesko, director of the Office of Clinical Pharmacology at FDA's Center for Drug Evaluation and Research, told participants at the Drug Information Association meeting in Philadelphia last week.

Lesko also said that:

  • The rate of VGDS submissions — about one per month — has remained stable.
  • Only a few pharmas have submitted more than once, and they have found the most benefit from their first submission.
  • With one exception, none of the data submitted under the voluntary program has been resubmitted as part of a required review. Lesko noted, however, that given the timelines of drug development, the program is relatively new, so that no conclusions should be drawn yet.
  • Recently the submissions have been trending toward the pre-clinical arena.
  • Top therapeutic areas include cancer, Alzheimer's, and depression.
  • Top technical areas include genotyping, microarrays, and software validation.

— Dennis Waters

Sam Tetlow, author of the Cambridge Healthtech Institute report "Successful Pharmacogenomics Business Models," said "proteomics is not yet validated enough to be a source of biomarkers," but stressed "it's actually critical that you have a proteomics element to those data submissions."

But he said the FDA "gets it. They get that it's early, that having a safe harbor philosophy is appropriate and necessary, and they've been sticking by that."

He said it's "encouraging that the FDA is taking the 'VXDS' perspective and opening the barn door to have more forms of data be submitted."

Ron Salerno, director of experimental medicine and worldwide regulatory affairs at Wyeth Research and a key player in the FDA's pharmacogenomic strategies, said the VXDS moniker makes "a lot of sense because 'X' could stand for exploratory" as well.

He said researchers are developing and studying novel efficacy models "but there's no real formal avenue to discuss it with the FDA scientists until you submit an [investigational new drug] application," said Salerno. He said by expanding the VGDS to include other kinds of data the agency can "create an environment where we might explore the utility of biomarkers very, very early in development."

Salerno said proteomics "has its own standards and data limitations that need to be explored."

Asked whether the FDA may soon release a guidance document describing and codifying its perspective on proteomic biomarkers, Salerno said: "I don't know right now. But it would seem to me that there would be some kind of concept paper issued suggesting that we talk about this, and the next workshop can focus on this," he said. "But I'm sure we're a couple of years away from any specific guidance unique to proteomics or metabolomics."

Lesko did not return a request for comment.

— Kirell Lakhman ([email protected])

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