FDA is forming a pharmacogenomics advisory committee to handle voluntary genomic data submissions, Office of Clinical Pharmacology & Biopharmaceutics Director Lawrence Lesko, PhD, said.

"We're going to establish an advisory committee to deal with, in a public way, the information that's submitted" voluntarily by industry on pharmacogenomics, Lesko said at the Drug Information Association EuroMeeting in Prague March 11. "We're in the process of starting on that."

The committee is "not going to give away proprietary information, but things that we've learned from these voluntary submissions...that would benefit the industry collectively," he vowed.

The advisory committee idea was borne out of work on a draft pharmacogenomics guidance released in November. Comments submitted by the Biotechnology Industry Organization supported the development of an advisory committee to discuss general pharmacogenomics topics (¹ Also see "FDA Pharmacogenomics Guide Needs Process To Accept Biomarkers – PhRMA" - Pink Sheet, 23 February, 2004., p. 31).

Overall, Lesko said the comments submitted had been anticipated by FDA. "There was nothing in there that was a surprise....None of these are going to diminish the completion of this guidance."

FDA's target date for completing the final draft is June 30. "We're going to make that," he declared.

At the time the final guidance is released, FDA also intends to publish two "companion documents" on its website: one outlining a standard process for voluntary genomic data submissions and another on the proposed Interdisciplinary Pharmacogenomics Review Group.

The review group had been one area of concern for industry from the ² draft guidance. "We're going to write the charter for that Interdisciplinary Pharmacogenomics Review Group...to see what it's going to do, what its responsibilities are, who's on it, etc. - completely transparent," Lesko said.

The FDAer gave a preview of what the group would look like. "We have hired two senior scientists with genomics expertise to lead this group. They come from industry, they have technical backgrounds, and they have personal experience" with the issues. "The ordinary members of our PG working group make up the rest."

The second publication is intended to be a "process standard operating procedure for how to submit one of these voluntary submissions," Lesko said. "We want to make it as seamless as possible."

Another pharmacogenomics initiative underway is a guidance on combination drug/genomic test submissions. Lesko and Center for Devices & Radiological Health's Office of In Vitro Diagnostic Device Evaluation and Safety Director Steve Gutman, MD, are co-chairing the group developing the guidance.

"We hope to have something this year as a draft guidance and possibly a workshop on that draft guidance sometime in early 2005," Lesko said.

The guidance would address the approval pathway for a drug combined with a diagnostic genomics test, a model that could become more common as pharmacogenomics makes inroads into standard drug development.

Genentech's oncologic Herceptin is one example of a drug/test combo. Trastuzumab was approved to treat breast cancer in patients whose tumors overexpress the HER2 protein; the HercepTest diagnostic assay was simultaneously approved.

Lesko indicated that FDA is moving toward requiring more pharmacogenomic information in labeling.

"Another PG initiative which is picking up some momentum - and this is separate now from voluntary submissions - is to begin to strongly encourage pharmacogenomic information and testing for those in product labels," he said.

"So we're going to be paying close attention" and "asking questions about genomics testing, using validated, known biomarkers...whether it's a new drug or an old drug," he said. "There should be some mention in the label of the test being available."

Lesko cited Lilly's attention deficit/hyperactivity disorder drug Strattera as an example of a case where FDA required that labeling reference a laboratory test available to screen for poor metabolizers of the enzyme CYP2D6 (³ Also see "Strattera QTc Concerns Addressed During Review; Lilly Avoids Warning" - Pink Sheet, 14 April, 2003., p. 11).

Lesko discussed FDA's intention to develop a guidance on how best to include genetic tests in product labeling during a Pharmaceutical Science Advisory Committee meeting last year (⁴ Also see "Pharmacogenetic Data With Clinical Outcomes Should Be Described In Label" - Pink Sheet, 28 April, 2003., p. 11).

FDA is also in the process of directing the relabeling of all bio-purines in the marketplace to include information on a test for TPMT enzyme deficiency, Lesko said.

In July, advisory committee recommended the relabeling for Teva's Purinethol (6-mercaptopurine) to mention tests available for TPMT enzyme deficiency (⁵ Also see "GSK Purinethol Labeling Should Mention Tests For TPMT Enzyme Activity" - Pink Sheet, 21 July, 2003., p. 33).

FDA is also looking at MedWatch data and adverse event literature "to identify other approved drugs that are candidates for updating of older labels to include new information on genomic tests," Lesko said.

"The lead candidate in that category - although we have several - is the warfarin situation with adverse events and the way that 2C9 metabolizer status can inform a decision on using the drug."

Lesko noted that FDA is committed to a "multi-year and multi-dimensional approach to advancing genomics," regardless of who is chosen as the next commissioner.

FDA Commissioner McClellan is moving to head up the Centers for Medicare & Medicaid Services following his Senate confirmation March 12 (⁶ [A#00660110002], p. 4).

As one of his final proposals as FDA commissioner, McClellan announced a "Critical Path" initiative March 16, which references genomics as a significant opportunity in R&D.

Overall, Lesko indicated that FDA feels satisfied it is doing all it can to move along the use of pharmacogenomics in drug development - and that the ball is now in industry's court.

"I'm sort of coming to the conclusion there isn't much more we can do until we see some activity in terms of either a voluntary submission or a required submission," he said.

Industry is beginning to take some action; Wyeth and Elan submitted a gene expression study report from a failed Alzheimer's disease vaccine trial Feb. 25. The report was the first such voluntary submission under FDA's draft guidance.

The report was based on transcriptional profiling analysis of peripheral blood samples obtained during a clinical trial with AN1792, a vaccine investigated in mild to moderate Alzheimer's disease patients.

Wyeth and Elan discontinued development of the vaccine in January 2002 due to the incidence of encephalitis in trial subjects. Wyeth hopes to use the genomic data to develop other Alzheimer's therapies.

At the DIA meeting, Wyeth Senior Director-Regulatory Affairs Ron Salerno, PhD, noted that industry is planning to sponsor a pharmacogenomics-related workshop in April 2005.

FDA and industry have already cooperated on the topic; the agency and the Pharmaceutical Research & Manufacturers of America sponsored two pharmacogenomics workshops in May 2002 and November 2003.

Pharmacogenomics issues are also drawing increased attention outside the U.S. European Medicines Evaluation Agency Sector of Clinical Safety and Efficacy Deputy Head Marisa Papaluca Amati, MD, gave an update at the DIA EuroMeeting on EMEA's recent pharmacogenomics briefings with industry.

EMEA has run four such sessions with interested stakeholders and is planning two more for July. When asked whether FDA and EMEA would be taking a harmonized approach to the issue, both agencies agreed such an effort would be premature at present.

"What would you want agencies to harmonize on at this point in time? It would seem to me you harmonize on things you understand and you have a position on and you have experience with. I think it's probably a mistake to harmonize too early," Lesko said.

Amati suggested a possible step toward harmonization could be including FDA at EMEA's upcoming pharmacogenomics briefings. "If the sponsors coming in July want us to invite Larry, we might see whether he is available on that date," she said. "Let's start with simple things."

[Editor's Note: A version of this story first appeared in ⁷ 'The Pink Sheet' DAILY March 11. Visit our website, www.ThePinkSheetDAILY.com, to sign up for a free trial.]

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