NIH expects its small molecule database to provide drug development candidates to small biotechnology firms and disease foundations pursuing orphan indications.

"With most of the big pharma [companies] that I have talked to, they've said 'well, we would use the information in the database but we wouldn't use the compounds. We would make our own assay, do our own screening,'" National Human Genome Research Institute Senior Advisor Christopher Austin, MD, said at a Drug Information Association workshop on pharmacogenomics Nov. 13.

"Where I think that might not happen is with small biotechnology companies or disease foundations, who have told us that they don't have screening capacity and they actually would want to cherry-pick compounds in this collection potentially for orphan disease applications to actually develop," Austin said.

The small molecular database is being developed under the NIH's "Molecular Libraries" initiative, which is part of the agency's "roadmap to medical research."

Under the initiative, NIH will create "a common chemical repository for about 500,000 compounds in a series of five screening centers that will look very much like what's in pharma now," Austin said.

Researchers at the screening centers will "take in assays from the public sector mainly, do the screening, do a little bit of the medicinal chemistry, and put all the screening results, all the compounds into a publicly accessible database that everyone will have access to," he said.

Austin stressed the importance of public access to early-stage research findings.

"There has to be a better community-wide understanding of the value of early research findings," he said. "People in academia and universities often think very highly of very basic discoveries and cover them with [intellectual property] protection, which prevents them from being used as research tools."

"It is absolutely essential to have IP protection on truly valuable discoveries. But for early-stage research tools, these are just preventing the kind of work that has to be done, and it's going to be necessary to translate this tremendous motherload of information which the genome has given us into improvements in human health."

NIH is consulting with pharmaceutical and biotechnology firms on how to provide adequate intellectual property protection to manufacturers who wish to license and develop compounds from the database. "We're really trying to serve two masters here," Austin said, "but I think it is resolvable."

Austin's background gives him a perspective on the industry end of the research spectrum; he was director of genomic neuroscience at Merck before joining NIH in November 2002.

Pfizer Director of Molecular & Investigative Toxicology William Pennie, PhD, also expressed concern about balancing the benefits of public data against the challenges of protecting intellectual property.

"There's a big challenge in IP in this area. How are we going to be free to move forward or are we going to be constrained by patents that are held for signature gene expression changes?" he asked. "Who will hold the public databases that are used to put data in context? In a rapidly evolving era, how do we make those databases flexible enough to keep pace with changes in the technology?"

Austin said the task of finding practical applications for pharmacogenomic research is so large that the public sector will need to share some of the burden.

"The magnitude of the task of functionating the genome, that is understanding the biological function and therapeutic potential of those 100,000 to 200,000 targets, is so enormous that it's going to require a shift in tasks undertaken by the public and private sectors," Austin said.

"More target validation is going to have to be done in the public sector. There is no way that the private sector can do all of the target validation that needs to be done starting with very early-stage genetic discovery," he said.

FDA Commissioner McClellan also underscored the necessity of translating pharmacogenomic technology into medical therapies, painting a bleak picture of the future of drug development without genomics-driven treatments (see ¹ Also see "Drug Development Too Risky Without Pharmacogenomics, McClellan Says" - Pink Sheet, 17 November, 2003. ).

The agency issued a draft guidance on pharmacogenomics data submissions Nov. 3 and is expected to publish two more guidances on the topic (² Also see "FDA Genomics Guidance, Demographics Database To Improve Gender Analysis" - Pink Sheet, 3 November, 2003., p. 3).

At the DIA meeting, FDA Center for Drug Evaluation & Research Director Janet Woodcock, MD, addressed "policy questions" that have arisen concerning the guidance. Woodcock is currently on detail to the office of the commissioner; however, her interest in pharmacogenomics is highlighted by the fact that she is listed as an author on the draft guidance.

The guidance describes a voluntary submission provision for exploratory pharmacogenomics data, which would be kept confidential and would not be used in regulatory decision making by FDA. However, Woodcock said the agency would disclose the discovery of a valid biomarker should FDA receive findings from multiple sponsors that suggest a new biomarker has been identified.

"People say, 'well, what if FDA learns through multiple submissions by different sponsors that a test result constitutes a valid biomarker?' Well I would say, wouldn't everyone want to find out about that if that were true? So yes," Woodcock said.

"What we would do...is notify the people through the appropriate process, either public or confidential, depending on what kind of data we had and how public we could make it, that in fact we had enough knowledge to consider it a predictive marker," she said. "We would use a formalized process to do this."

"I think people are worried about it and thinking about it in a negative light," Woodcock said. "But I think if we find out that some marker actually predicts a serious toxicity and if that's true across a number of drug products, then we do have an obligation to tell everybody they ought to start looking for that. Probably people at the end of the day would thank us for doing that."

The CDER director said "new requirements...as far as the ordinary process of drug development, is not going to happen soon," with the "early exception [of] maybe cancer treatment...where you're getting gene sequence expression data in the tumor."

Public Genomics Data Needed, FDA, NIH Say; Patent Protection Still An Issue

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