The US Food and Drug Administration has been receiving an average of two voluntary genomic data submissions each quarter from drug makers since the VGDS program went into effect two years ago, and the agency is content with the pace, an agency official said this week.
But this current level of sponsor participation may mean that the initiative is not a top priority for pharma, even as drug makers feel comfortable enough with the program to submit increasingly complex data.
According to Felix Frueh, head of the FDA’s Interdisciplinary Pharmacogenomics Research Group, the number of voluntary submissions has remained at a steady level “between two or three per quarter” since the program began in 2004.
The level of participation, considered low by general industry standards, does not reflect a lack of commitment toward VGDS at the agency, Frueh said. Rather, it may suggest that the VGDS program is “not a high priority” for drug companies since “these submissions aren’t submissions that industry is using for making regulatory decisions,” Frueh told Pharmacogenomics Reporter this week.
In a Sept. 28 presentation on the VGDS program during a Drug Information Association conference, Frueh said one of the program’s “limitations” is that it is “not a high [industry] priority.” Frueh spoke with Pharmacogenomics Reporter this week to flesh out comments he made during the conference.
Slow and Steady Wins the Race?
Frueh, who is also associate director of the Center for Drug Evaluation and Research, seemed to approve of industry’s level of participation in VGDS, noting that significantly ramping up the number of submissions is not something the agency or companies feel “would make a lot of sense.”
From the FDA’s perspective, two to three VGDS per quarter is “plenty to look at a broad spectrum of how genomics is used in drug development and into the various possibilities of analyzing the data sets,” Frueh said.
FDA enacted its VGDS program in 2004 as a way to learn how drug makers use various pharmacogenetic technologies. The agency has pledged not to use the data in its review process.
However, Frueh noted that drug companies are using the VGDS program to inform their internal strategy for advancing investigational agents or as a tool to pick the agency’s brain on various clinical approaches.
“The fact that the number of VGDS has remained constant I think demonstrates it’s a case-by-case, occasion-driven way to interact with the agency,” he continued. “Many of the submissions are very substantial and very labor intensive for us to review.
“As a matter of fact, we could not handle more than what we get at the moment,” Frueh added. “Maybe one more per quarter and that would be it. We’re pretty much at the limit of what we can analyze because we have an increasing workload from non-voluntary submissions as well.”
Since the program launched, the FDA has received a total of 25 submissions and held 15 “consults” for genomic review for regular IND, NDA, or BLA type submissions. According to Frueh, while the number of VGDS submissions has remained static, there has been an “exponential” jump in consults, from one such meeting with sponsors in the fourth quarter of 2004 to 10 consults in the first quarter of 2006.
“The increase in the number [of consults] indicates that (1) industry is increasingly using genomics in drug development and decision making, and (2) that there is an increasing level of comfort to share that information with regulators (again, indicating that this information in fact is being used for regulatory decision making),” Frueh said in an e-mail.
Multiple VGDS from several drug companies is another sign that pharmas are warming up to the program. Frueh mentioned that several companies have followed up submissions with updated data, and two or three firms have submitted entirely new data a second time.
“Certain companies have submitted voluntary submissions more than once, which tells me that their initial experience was probably not so bad that they said, ‘Oh, God, we’ve done that once, never go back there again,’” Frueh said. “So they must have gotten something out of it that was valuable.”
The companies who have participated in the VGDS program more than once are mostly big pharmaceutical firms, Frueh noted. The participation of big pharma in VGDS is another sign that the program is moving forward, however slowly. Initially, companies like Pfizer, Johnson & Johnson, GlaxoSmithKline, and Roche took issue with FDA’s draft “Guidance for Industry: Pharmacogenomic Data Submissions” saying it “is not workable in its current format” and that the entire VGDS process ought to “be removed from the proposed guidance at this time.” [PGx Reporter 03-04-04
Industry’s growing ease with VGDS is further evident in the increasing complexity of the data that sponsors submit to the agency. In 2004, sponsors would submit summaries and little or no raw data, said Frueh. “Today it’s significantly different … because we are now getting submissions with several hundred microarray raw data sets, and the clinical information that comes with it look at genotype/phenotype relationships,” he said.
Drug companies are using the VGDS program to inform their internal strategy for advancing investigational agents or as a tool to pick the agency’s brain on various clinical approaches.
“So the comfort level of industry to submit that type of information has gone up tremendously over the last 18 months, when they saw what FDA is doing with that information, what we are able to give back to sponsors. So the reluctance of submitting that information to FDA that probably existed two years ago is going away,” he added.
FDA Introduces VGDS’ ‘X’ Factor
Along with industry, FDA also appears increasingly at ease with VGDS. The agency recently expanded VGDS to VXDS, which would allow sponsors to submit “exploratory” biomarkers such as proteomics, metabolomics, and imaging data. VXDS is fully implemented at FDA and the agency has obtained the necessary resources and expertise, Frueh said.
The VGDS program’s expansion to include VXDS has been long under discussion at FDA. Larry Lesko, director of the Office of Clinical Pharmacology at FDA’s Center for Drug Evaluation and Research, told participants at DIA’s annual meeting in June that it may be time for the agency to “rethink” the VGDS program to include other kinds of biomarker data.
With VXDS, FDA will accept exploratory data submissions either for single disciplines or for cross-comparisons of genomics, proteomics, or metabolomics data. The latter is of particular interest to the agency since it can show how different types of biomarkers “can be useful at various stages in drug development and how one type relates to the other,” Frueh said. He added the agency has received two such cross-disciplinary submissions, involving preclinical data and oncologic data.
In certain “therapeutic areas, “one type of biomarker may be better than others. If you look at oncology, if you have a solid tumor you may look at a gene expression profile, but if you have a non-solid tumor you might look at a protein that can be measured in peripheral blood, that may be more accurate as a biomarker than a gene expression profile,” Frueh explained. “So, we realized that depending on the application, you might actually use different types of biomarkers.”